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Find an Expert Immunologist

Since 1987, the Jeffrey Modell Foundation has created a Network of the world’s leading Expert Immunologists to help point you in the right direction. What makes our Network thrive is the brilliance and compassion of the physicians, the resolve and dedication of the researchers, and the perseverance of the quiet, unsung heroes working days and nights in their labs.

Use the tool below to find an Expert Immunologist in your area.


If you have any problems finding an Expert Immunologist, please email us at info@jmfworld.org

Please note that the information in this directory does not constitute a recommendation to consult any specific physician. The inclusion of physicians and centers does not necessarily attest to a physician’s expertise in treating a specific Primary Immunodeficiency. Any questions regarding a healthcare provider’s qualifications and experience should be directed to that healthcare provider.

Physicians and Centers interested in becoming a part of our Jeffrey Modell Centers Network should please email us with your contact information at info@jmfworld.org.

About Primary Immunodeficiency

The Immune System

It’s our only defense... but it doesn’t work for everyone. Each and every day, your body fights off infections, germs, bacteria, and viruses. These invaders, called pathogens, are destroyed by the body’s number one defense, the immune system. Some people are born with immune systems that don’t work as well as others. This could be due to Primary Immunodeficiency, which might cause a person to be sick more often than others.

What is Primary Immunodeficiency?

Primary Immunodeficiencies are a group of more than 450 disorders of the immune system with varying degrees of severity. They occur when one or more essential parts of the immune system do not work correctly.

People with Primary Immunodeficiency cannot get rid of pathogens or protect themselves from these pathogens as well as they should, causing frequent infections and other problems that are hard to cure. Infections may appear to be common illnesses such as sinus and ear infections, pneumonia, fever, common colds, and bronchitis. 

Why Getting Help Is Important

Today patients with Primary Immunodeficiency are able to gain and maintain control of their lives with treatment and intervention:

They are able to participate in work, school, family, and social activities.

  • They have fewer and less severe infections.
  • They feel good about their treatment programs and, most importantly, themselves.

Failure to diagnose Primary Immunodeficiency can lead to an increased number and severity of infections, frequent interruptions in work, school, family, and social activities, and a lifetime of serious illness, including permanent organ damage. There are many treatment options that can help patients diagnosed with Primary Immunodeficiency lead healthier lives.

10 Warning Signs of Primary Immunodeficiency

  1. Four or more new ear infections within 1 year.
  2. Two or more serious sinus infections within 1 year.
  3. Two or more months on antibiotics with little effect.
  4. Two or more pneumonias within 1 year.
  5. Failure of an infant to gain weight or grow normally.
  6. Recurrent, deep skin or organ abscesses.
  7. Persistent thrush in mouth or fungal infection on skin.
  8. Need for intravenous antibiotics to clear infections.
  9. Two or more deep-seated infections including septicemia.
  10. A family history of Primary Immunodeficiency

Your Body’s Best Defense

Every day, your body fights off infections, germs, bacteria, and parasites. It is destroying these invaders, called pathogens, with the help of its number one defense: the immune system. The immune system’s job is to keep your body healthy. This requires many different parts of the body to work together against pathogens. Here are the main components of your immune system:

Tonsils

Located in the back of your throat, the tonsils protect the entrance to your respiratory and digestive systems by destroying bacteria with the help of white blood cells.

Thymus Gland

Located underneath the middle of your breastbone and above your heart, the thymus gland stores white blood cells until they are mature, and then provides them with specific jobs.

Lymph Nodes

Small, bean-shaped modules on the lymphatic vessels, lymph nodes are located primarily in your armpits and groin regions. They filter pathogens out of the lymphatic system.

Bone Marrow

Located inside your body's bones, it produces red and white blood cells. Red blood cells carry oxygen to other cells and body parts and remove carbon dioxide. White blood cells look for and destroy pathogens. The different types of white blood cells are phagocytes, B cells, and T cells.

Spleen

The largest lymphoid organ in the lymphatic system, the spleen is located to the left of your stomach. The spleen removes pathogens from the blood as it passes through.

Liver

Your body's largest internal organ, the liver contains white blood cells. These cells destroy bacteria in the blood as it passes through the liver. It also processes nutrients found in the blood and produces bile used in digestion.

Blood

Red and white cells travel throughout your body's blood vessels. While white blood cells defend against pathogens, your red blood cells nourish your body.

Primary Immunodeficiency Definitions

Specific Primary Immunodeficiencies 

We understand it can be overwhelming to process and learn about the different Primary Immunodeficiencies. To help make it easier, this section provides detailed definitions for the specific Primary Immunodeficiencies.

Choose from one of the specific Primary Immunodeficiency definitions below:

ADA Deficiency

Adenosine Deaminase (ADA) Deficiency is an autosomal recessive condition that causes Severe Combined Immune Deficiency (SCID). ADA Deficiency is characterized by frequent and persistent severe infections. This condition is fatal if those affected do not receive treatment through hematopoietic stem cell transplantation (HSCT). Gene therapy and enzyme replacement therapy are additional treatment options.

Learn more about ADA Deficiency

APDS - Activated P13K Delta Syndrome

APDS, or Activated P13K Delta Syndrome, is a rare primary immunodeficiency that affects 1-2 people in a million. APDS occurs when there is an abnormal change in either one of two specific genes, the PIK3CD gene or the PIK3R1 gene.  The genes follow an autosomal dominant mode of inheritance and are involved in making parts of a protein that help in the growth and division of white blood cells, particularly the B-cell and T-cell lymphocytes. The changes in these genes lead to the creation of an enzyme (PI3KD) that is more active than normal, causing abnormal development and control of B- and T-lymphocytes; as a result, their ability to recognize, prevent, or fight off bacterial and viral infections is reduced. Symptoms of APDS start in childhood, and patients are vulnerable to repeat infections and autoimmune/inflammatory symptoms such as lymphoproliferation, splenomegaly, and even lymphoma.  Cases of short syndrome and neurological cognitive deficit has also been observed.  Patients are often misdiagnosed with other immunodeficiencies or autoimmune disorders. Diagnosis is made by a genetic test, and regular health checkups are required. Clinical trials are underway to find a treatment for APDS.

To learn more about APDS and steps to diagnosing the condition, including information about a recently launched sponsored genetic testing program, please visit www.allaboutapds.com

Artemis Deficiency

Artemis Deficiency causes one of the most aggressive forms of Severe Combined Immune Deficiency (SCID), characterized by absence of B cells and T cells. This form of SCID is caused by mutations in the Artemis gene inherited in an autosomal recessive pattern. Infants with Artemis Deficiency experience severe, life-threatening infections, and oral/genital ulcers. This condition is fatal in the first year of life if not treated with bone marrow transplantation.

Learn more about Artemis Deficiency:

Ataxia Telangiectasia

Ataxia Telangiectasia is a disorder inherited in an autosomal recessive pattern that affects the immune system and nervous system. It is caused by a mutation in the ATM gene. Symptoms usually present before the age of 5 and include difficulty with movement, coordination, and balance. Children with Ataxia Telangiectasia also have weakened immune systems and are at increased risk of developing cancers such as Leukemia and Lymphoma. Approximately 1 in 40,000 to 1 in 100,000 are affected by Ataxia Telangiectasia globally.

Learn more about Ataxia Telangiectasia:

Autoimmune Lymphoproliferative Syndrome (ALPS)

Autoimmune Lymphoproliferative Syndrome (ALPS) is a genetic disorder most commonly caused by a mutation in the FAS gene. ALPS is characterized by the overproduction of lymphocytes, causing enlargement of the lymph nodes, spleen, and liver. Symptoms may include arthritis, skin rashes, and neurologic damage, as well as increased susceptibility to autoimmune disorders and cancers. ALPS- FAS is generally passed on in an autosomal dominant pattern.

Learn more about ALPS Deficiencies:

Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED)

Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) is a genetic condition caused by mutations in the AIRE gene inherited in autosomal recessive patterns. APECED is characterized by chronic candida infections, autoimmune hypoparathyroidism, and Addison’s Disease. It is mostly prevalent in Finnish, Iranian Jewish, Norwegian, and Sardinian populations.

Learn more about APECED:

C1 Inhibitor Deficiency

C1 Inhibitor Deficiency is an autosomal dominant Primary Immunodeficiency that causes inflammation in the respiratory and gastrointestinal tracts. People with C1 Inhibitor Deficiency may show signs and symptoms early in life, and usually have a family history. Clinically, C1 Inhibitor Deficiency is characterized by angioedema, accumulation of fluid in the larynx, and gastrointestinal tract inflammation. There are over 100 gene mutations that cause this deficiency. Approximately 1 in 50,000 people are affected worldwide.

Learn more about C1 Inhibitor Deficiency:

Cartilage Hair Hypoplasia

Cartilage Hair Hypoplasia is a condition caused by mutations in the RMRP gene, which is inherited in an autosomal recessive pattern. Mutations in the RMRP gene cause an overproduction of RNA, which interferes with normal cell function. Characteristics of Cartilage Hair Hypoplasia include abnormal skeletal growth, short stature, fine and thinning hair, as well as recurring infections and gastrointestinal dysfunction.

Learn more about Cartilage Hair Hypoplasia:

Chediak-Higashi Syndrome

Chediak-Higashi Syndrome is a genetic condition caused by a mutation in the LYST gene, inherited in an autosomal recessive pattern. This condition is characterized by an abnormal function of proteins that control production of lysosomes, leading to interference of normal cell function and poor immune system function. Chediak-Higashi Syndrome is characterized by frequent infections, oculocutaneous albinism (abnormal pigmentation), vision problems, frequent bruising, and abnormal bleeding.

Learn more about Chediak-Higashi Syndrome:

Chronic Granulomatous Disease

Chronic Granulomatous Disease is a Primary Immunodeficiency in which affected individuals have recurrent viral and bacterial infections, most commonly in the lungs. Individuals with Chronic Granulomatous Disease often have inflammation in tissues within the gastrointestinal and genitourinary tracts that can be damaging. Chronic Granulomatous Disease is caused by genetic mutations inherited in X-linked recessive and autosomal recessive patterns. Symptoms may include abscesses, difficult to clear skin infections, bone and joint infections, persistent diarrhea, and frequent pneumonias.

Learn more about Chronic Granulomatous Disease:

Chronic Mucocutaneous Candidiasis

Chronic Mucocutaneous Candidiasis is caused by mutations in genes inherited in both autosomal recessive and dominant patterns. Mutations in the AIRE gene (autoimmune regulator) cause autosomal recessive inherited CMC, while mutations in STAT1 underlie autosomal dominant inherited CMC. Characteristics include candida infections of the skin, mucous membranes, and nails.

Learn more about Chronic Mucocutaneous Candidiasis:

Clinical Trial Opportunity for Patients with Chronic Mucocutaneous Candidiasis

Chronic Mucocutaneous Candidiasis often results from an underlying immune deficiency that leads to abnormalities in a person’s control of fungal infections such as candida. Investigators at NIAID are seeking people with chronic mucocutaneous candidiasis (oropharyngeal, esophageal or vulvovaginal candidiasis) that are refractory or intolerant to standard non-intravenous therapies to participate in a clinical research trial. For additional information please contact Dr. Alexandra Freeman (freemaal@mail.nih.gov) or see https://clinicaltrials.gov/ct2/show/NCT02629419.

Comel-Netherton Syndrome

Comel-Netherton Syndrome is a disorder caused by mutations in the SPINK5 gene, which is inherited in an autosomal recessive pattern. Comel-Netherton Syndrome is characterized by abnormal skin (eczema, itching, scaly edges, inability to protect from the heat and cold), hair (rigid, bamboo-like shafts), and immune system (allergies, short stature, high serum levels of IgE).

Learn more about Comel-Netherton Syndrome:

Common Variable Immunodeficiency

Common Variable Immunodeficiency is characterized by frequent bacterial infections, commonly of the upper and lower respiratory tracts, low levels of immunoglobulin, and B-cell dysfunction. Specifically, people with Common Variable Immunodeficiency (CVID) have increased occurrences of pneumonias, sinusitis, influenza, and gastrointestinal inflammation. CVID is diagnosed by measuring for low serum IgG, and sometimes reduced concentration in IgA and IgM. Some people with CVID may also have autoimmune manifestations. Signs and symptoms may develop in childhood, though many are diagnosed in adulthood.

Learn more about Common Variable Immunodeficiency:

Complement Deficiencies

Complement Deficiencies are caused by genetic defects of the innate immune system. People with Complement Deficiencies are susceptible to recurrent bacterial infections and sepsis. Autoimmune disorders may also manifest, such as Systemic Lupus Erythematosus.

Learn more about Complement Deficiencies:

DiGeorge Syndrome

DiGeorge Syndrome is caused by a deletion of genes on chromosome 22. Symptoms of DiGeorge Syndrome may include frequent infections, heart complications, thyroid dysfunction, poor muscle tone, failure to thrive, delayed development, and cleft palate. Treatments are available for complications that may arise from DiGeorge Syndrome.

Learn more about DiGeorge Syndrome:

EDA-ID, X-Linked Deficiency

Anhidrotic Ectodermal Dysplasia with Immune Deficiency (EDA-ID) is a group of conditions characterized by lack of immunoglobulins and abnormal development of the skin, teeth, hair, and sweat glands. EDA-ID, X-Linked is caused by mutations in the IKBKG gene, which is inherited in a recessive pattern, affecting mostly males. Symptoms include frequent pneumonias, sinusitis, inflammatory bowel disease, skin abnormalities (dry, wrinkled appearance), and teeth abnormalities (small and pointed in appearance). This condition is associated with NEMO (NF-kappa B essential modulator) mutations.

Learn more about EDA-ID X-linked Deficiency:

ELANE-Related Deficiencies

ELANE-Related Deficiencies cause congenital neutropenia, which is characterized by frequent fevers, inflammation, ulcers, sinusitis, pharyngitis, deep abscesses in organs, pneumonias, and diarrhea. Congenital neutropenia is often diagnosed in the first year of life. Mutations in the ELANE gene are inherited in an autosomal dominant pattern.

Learn more about ELANE Deficiencies:

Familial Hemophagocytic Lymphohistiocytosis

Familial Hemophagocytic Lymphohistiocytosis (FHL) is a condition caused by several genetic mutations inherited in autosomal recessive patterns. FHL is characterized by overproduction of T cells, B cells, Natural Killer cells, and macrophages, causing fever, spleen and liver damage, abnormal bleeding, and frequent bruising.

Learn more about FHL and related Perforin Deficiencies:

Familial Mediterranean Fever

Familial Hemophagocytic Lymphohistiocytosis (FHL) is a condition caused by several genetic mutations inherited in autosomal recessive patterns. FHL is characterized by overproduction of T cells, B cells, Natural Killer cells, and macrophages, causing fever, spleen and liver damage, abnormal bleeding, and frequent bruising.

Learn more about FHL and related Perforin Deficiencies:

Griscelli Syndrome

Griscelli Syndrome is a disorder caused by mutations in the MYO5A, RAB27A, and MLPH genes, which are inherited in an autosomal recessive pattern. Type 2 (RAB27A) is the most frequent type of Griscelli Syndrome, characterized by recurrent infections, organ and tissue damage, and abnormalities in pigmentation of hair and skin.

Learn more about Griscelli Syndrome:

Hermansky-Pudlak Syndrome

Hermansky-Pudlak Syndrome is caused by mutations in several genes, inherited in an autosomal recessive pattern. Hermansky-Pudlak Syndrome is characterized by oculocutaneous albinism, causing abnormal pigmentation of the eyes, skin, and hair. Symptoms may also include vision problems, sensitivity to light, frequent bruising and abnormal bleeding, and issues with breathing caused by pulmonary fibrosis.

Learn more about Hermansky-Pudlak Syndrome:

Hyper IgD Syndrome

Hyper IgD Syndrome is a condition caused by mutations in the MVK gene and is inherited in an autosomal recessive pattern. Hyper IgD Syndrome is characterized by periodic fevers, skin rashes, abdominal and joint pain. Episodes of periodic fever usually occur in infancy.
 

Learn more about Hyper IgD Syndrome:

Hyper IgE Syndrome, Autosomal Dominant

Hyper IgE Syndrome, also known as Job Syndrome, is a deficiency that causes overproduction of serum IgE. Autosomal Dominant Hyper IgE Syndrome is caused by a mutation in STAT3, leading to abnormalities in skin (rashes, boils), the skeleton (scoliosis, fractures, hyperextension of joints), and of the vasculature (aneurysms).

Learn more about Autosomal Dominant Hyper IgE Syndrome:

Hyper IgE Syndrome, Autosomal Recessive

Hyper IgE Syndrome is a deficiency that causes overproduction of serum IgE. Autosomal Recessive Hyper IgE Syndrome is caused by mutations in the DOCK8 gene, leading to abnormalities in skin (rashes, boils), frequent pneumonias, and higher susceptibility to viral infections such as Herpes Simplex Virus.

Learn more about Hyper IgE Syndrome, Autosomal Recessive:

Hyper IgM Syndrome

Hyper IgM Syndrome causes abnormal levels of proteins called antibodies or immunoglobulin. It is usually inherited as an X-Linked recessive trait, predominantly affecting males. X-Linked Hyper IgM is caused by mutations in the gene that controls production of the protein CD40 ligand. There are different types of antibodies with different functions. In this case, patients have abnormally low levels of immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin E (IgE). Low levels of these antibodies make it difficult to fight off infections. Symptoms present themselves in infancy and early childhood. Patients often suffer from pneumonia, sinusitis, and otitis. Growth and weight gain are also affected. This syndrome occurs in about 2 in 1 million newborn boys. 

Learn more about X-Linked Hyper IgM Syndrome:

Hypogammaglobulinemia

Hypogammaglobulinemia is characterized by recurrent infections normally prevented by appropriate antibody response. Infections of the upper and lower respiratory tract (such as pneumonia, sinusitis, and bronchitis), gastrointestinal tract, skin, and joints occur more frequently for people with Hypogammaglobulinemia. Quantitative measurements of serum immunoglobulins can assist in diagnosis of Hypogammaglobulinemia. Treatment may include IgG replacement therapy.

Learn more about Hypogammaglobulinemia:

IgA with IgG Subclass Deficiency

IgG Subclass Deficiencies affect the production of antibodies. Many patients with IgA Deficiency are asymptomatic. However, respiratory, ear, and sinus infections may occur more frequently in patients who also have IgG Subclass Deficiencies. Onset of infections may occur later in life. Males and females can both be affected.

Learn more about IgA with IgG Subclass Deficiencies:

IgG Subclass Deficiency

There are a total of 5 subclasses of immunoglobulins (IgA, IgD, IgE, IgG, and IgM). IgG Subclass Deficiency is characterized by low serum levels for one or more immunoglobulins, with normal levels of remaining immunoglobulins. IgG is the most abundant immunoglobulin which circulates in the blood. Symptoms tend to be milder for people with IgG Subclass Deficiency, but may include increased susceptibility to respiratory infections.

Learn more about IgG Subclass Deficiency:

IPEX and IPEX-like syndromes

IPEX Syndrome is caused by mutations in the FOXP3 gene, which is inherited in an X-Linked recessive pattern. This disorder is characterized by the development of autoimmune disease, which affects mostly the intestines, endocrine glands, and skin. Symptoms include enteropathy, severe diarrhea, and failure to thrive. Type 1 Diabetes and Thyroid Disease may also be presenting clinical features of IPEX Syndrome. IPEX-link syndromes present similar symptoms as IPEX Syndrome, but the genetic cause is unknown.

Learn more about IPEX syndromes:

JAK3 Deficiency

JAK3 Deficiency is a form of Severe Combined Immune Deficiency (SCID), which is inherited in an autosomal recessive pattern. Mutations in the JAK3 gene cause the absence of T cells and Natural Killer cells, and dysfunction in B cells. SCID due to JAK3 Deficiency is characterized by high susceptibility to life-threatening infections, failure to thrive, chronic diarrhea, and graft-versus-host reactions to maternal T cells. This condition is fatal in the first 2 years of life if not treated with a bone marrow transplant.

Learn more about JAK3 Deficiency:

Leukocyte Adhesion Deficiency

Leukocyte Adhesion Deficiency is characterized by leukocytosis (increased white blood cell count) and recurrent, life-threatening bacterial infections. LAD is often fatal. Infants with LAD have failure to express CD18, a vital immune system component. LAD type II is typically seen in the Middle Eastern population. Bone marrow and stem cell transplantation is an effective therapy for patients with LAD.

Learn more about Leukocyte Adhesion Deficiency:

Leukocyte Adhesion Deficiency-I Clinical Features

LAD-I-diagnosis-handout-resize-900x1185-5c59f2125cef2-original.jpg

MHC Class II Deficiency

Major Histocompatibility Complex Class II Deficiency, also known as Bare Lymphocyte Syndrome, is a Severe Combined Immune Deficiency (SCID) characterized by a lack of human leucocyte antigen Class II gene expression, absence of humoral and cellular T-cell response to foreign antigens, and impaired antibody production. Patients with MHC Class II Deficiency are lacking CD4 T cells and are susceptible to viral, bacterial, and fungal infections. MHC Class II Deficiency is inherited as an autosomal recessive trait, and is caused by impaired gene regulation.

Learn more about MHC Class II Deficiency:

Nijmegen Breakage Syndrome

Nijmegen Breakage Syndrome is caused by mutations in the NBN gene inherited in an autosomal recessive pattern. These mutations cause abnormal development of Nibin protein, which causes abnormal response of repairs of DNA damage. This lack of response causes irregular cell division and growth. Nijmegen Breakage Syndrome is characterized by microcephaly, short stature, developmental disabilities, as well as an increased susceptibility to respiratory infections and cancer.

Learn more about Nijmegen Breakage Syndrome:

NK Cell Deficiency

Natural Killer Cell Deficiencies can be categorized as “classical” and “functional.” Classical NK Cell Deficiencies relate to the quantity of NK cells in the blood, and are caused by mutations in the GATA2 and MCM4 genes. Functional NK Cell Deficiencies relate to the quality of function of NK cells and are caused by mutation in the CD16 gene. NK Deficiencies are characterized by recurring and severe viral infections including Herpes Simplex Virus, Cytomegalovirus, Epstein- Barr Virus, and Human Papilloma Viruses.

Learn more about NK Cell Deficiencies:

Omenn Syndrome

Omenn Syndrome is a form of Combined Immune Deficiency characterized by high susceptibility to viral, bacterial, and fungal infections, failure to thrive, alopecia, and chronic diarrhea. Omenn Syndrome is inherited in an autosomal recessive pattern. It is a fatal condition if patients are not treated with bone marrow transplantation or hematopoietic stem cell transplantation (HSCT).

Learn more about Omenn Syndrome:

PFAPA Syndrome

Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis Syndrome (PFAPA) is a syndrome with recurrent episodes of fever, mouth sores, and sore throats. Fevers can last up to 3 to 7 days and occur every few weeks in addition to joint and abdominal pain, rash, headache, vomiting, and diarrhea. This disease can last for several years, but typically resolves itself later in life. Symptoms usually occur during the ages of 2 to 5. Studies show that a tonsillectomy, a removal of the tonsils, cures about 80 percent of patients.

Learn more about PFAPA Syndrome:

RAG1 and RAG2 Deficiency

RAG1 and RAG2 (recombination activation genes) play an essential role in recombination of immunoglobulin and T-cell receptor genes. These proteins work together to contribute to V(D)J recombination activity, which allows proteins to match antigens present in viruses, bacteria, parasites, and tumor cells. Lack of expression in RAG1 and RAG2 causes dysfunction in this activity, leaving those affected to experience severe infections. Patients with these defects have Severe Combined Immune Deficiency (SCID), with no B- or T-cell function.

Learn more about RAG1 and RAG2 Deficiencies:

Selective IgA Deficiency

Selective IgA Deficiency is the most common Primary Immunodeficiency. IgA is an essential immunoglobulin in the respiratory and gastrointestinal tracts that plays an important role in developing mucosal immunity and protection against infection. Selective IgA can be characterized by increased incidence of recurrent pneumonias, sinusitis, ear infections, and gastrointestinal infections, and may cause Autoimmune Diseases.

Learn more about Selective IgA Deficiency:

Severe Combined Immune Deficiency (SCID)

Severe Combined Immune Deficiency (SCID) is a group of disorders characterized by little or no immune response. Also known as the “bubble boy” disease, individuals with SCID are highly susceptible to severe bacterial, viral, and fungal infections. Symptoms include common pneumonias, chicken pox, meningitis, recurrent diarrhea, and failure to thrive. SCID is fatal in the first 2 years of life if not treated with a hematopoietic stem cell transplantation or gene therapy.

Learn more about Severe Combined Immune Deficiency:

Shwachman-Diamond Syndrome

Shwachman-Diamond Syndrome is caused most frequently by mutations in the SBDS gene, which is inherited in an autosomal recessive pattern. Shwachman- Diamond Syndrome is characterized by dysfunction of the bone marrow, causing neutropenia, which may lead to recurring ear infections and pneumonia. Patients with this syndrome are also more likely to develop anemia and blood cancers (Acute Myeloid Leukemia). Some individuals may also have pancreatic and skeletal abnormalities, as well as complications of the endocrine system.

Learn more about Shwachman-Diamond Syndrome:

Specific Antibody Deficiency

Specific Antibody Deficiency is characterized by lack of antibodies that assist in fighting off infection. The exact cause and manifestations are not completely known. However, it is hypothesized that Specific Antibody Deficiency causes B cells to not communicate properly with other immune cells for appropriate function. People with Specific Antibody Deficiency may experience increased susceptibility to respiratory tract infections.

Learn more about Specific Antibody Deficiency:

TACI Deficiency

Transmembrane Activator and Calcium-modulator and Cyclophilin Ligand Interactor (TACI) promotes antibody production and mediates isotype switching in B cells. Deficiencies in TACI cause Common Variable Immunodeficiency (CVID), which is characterized by recurrent infections, especially of the respiratory tract.

Learn more about TACI Deficiency:

TNF Receptor-Associated Periodic Syndrome (TRAPS)

Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) is caused by mutations in the TNFRSF1A gene and is inherited in an autosomal dominant pattern. TNFRSF1A controls signaling patterns that cause cells to initiate inflammation, production of cytokines, and cell death (apoptosis). This condition is characterized by periodic episodes of fevers, which usually last approximately 3 weeks. These episodes can be triggered by stress, infection, and changes in hormones. Other symptoms may include edema, joint pain, and skin rashes. Initial episodes generally occur in infancy and childhood, and can continue throughout adulthood.

Learn more about TRAPS:

WHIM Syndrome

WHIM syndrome is a rare and difficult-to-diagnose primary immunodeficiency in which the body’s immune system does not function properly and has trouble fighting infections. Some doctors also call primary immunodeficiencies inborn errors of immunity, which are genetic mutations that cause immunodeficiencies. WHIM syndrome is caused by mutations in the CXCR4 gene which causes white blood cells to get trapped in the bone marrow.

WHIM syndrome was named after four symptoms that most diagnosed patients have experienced: Warts, Hypogammaglobulinemia, Infections, Myelokathexis. There are no existing treatments that specifically target the underlying problem of WHIM syndrome—new treatments are needed.

Learn more about WHIM Syndrome:

Wiskott-Aldrich Syndrome

Most commonly found in males, Wiskott-Aldrich Syndrome is an immune deficiency that reduces the ability for the blood to clot. This abnormality is usually present at birth and leads to bruising easily and episodes of prolonged bleeding after a minor injury. This defect causes many types of white blood cells to be abnormal or nonfunctional, which leads to a risk of several immune and inflammatory disorders.

Learn more about Wiskott-Aldrich Syndrome:

X-Linked Agammaglobulinemia

X-Linked Agammaglobulinemia (XLA) is a condition that affects 1 in 200,000 newborns, primarily males. These individuals have very few B cells. B cells are specialized white blood cells that help the body protect itself against infection. These cells mature and produce proteins such as antibodies or immunoglobulins. Antibodies are needed to mark foreign germs and infections for destruction. Without these proteins, patients with XLA are extremely susceptible to infection. The most common infections are ear, pneumonia, conjunctivitis, and sinusitis. With treatment, infections can be avoided.

Learn more about X-Linked Agammaglobulinemia:

X-Linked Lymphoproliferative Disease

X-Linked Lymphoproliferative Disease (XLP) is a disorder of the immune system and blood-forming cells. It is a recessive trait, affecting more males. About 50 percent of these patients that are exposed to Epstein-Barr Virus (EBV), more commonly known as Mononucleosis, tend to develop a plethora of T cells, B cells, and macrophages. This mass production of immune cells causes a life-threatening response known as hemophagocytic lymphohistocytosis, which causes fever, destruction of blood-producing cells in the bone marrow, and liver damage. For some patients, this response can occur without even being exposed to EBV. In addition, abnormal levels of antibodies make these patients prone to many different types of infection and, without allogeneic stem cell transplantation or the replacement of blood-forming cells, many pass away during childhood.

Learn more about X-Linked Lymphoproliferative Disease:

X-Linked SCID

Affecting at least 1 in every 50,000 to 100,000 male newborns, X-Linked Severe Combined Immune Deficiency (SCID) is the most common form of SCID. This disorder is an inherited defect of the immune system causing a lack of T cells, B cells, and Natural Killer cells. Due to these cell deficiencies, afflicted infants are prone to infections that would not cause illness in a healthy individual, but is life-threatening for a person with X-Linked SCID. Without treatment, patients do not live beyond infancy.

Learn more about X-Linked SCID:

ZAP-70 Deficiency

ZAP-70 Deficiency is caused by mutations inherited in an autosomal recessive pattern, and presents as a form of Severe Combined Immune Deficiency (SCID). The ZAP-70 gene is involved in T-cell receptor signaling, which plays an essential role in T-cell differentiation and the development of T-cell function. Symptoms include susceptibility to severe bacterial, viral, and opportunistic infections, and failure to thrive. This condition is fatal without hematopoietic stem cell transplantation (HSCT) in the first year of life.

Learn more about ZAP-70 Deficiency:

γc (IL-2RG) Deficiency

Mutations in the gamma chain of the IL-2 receptor causes an X-Linked Severe Combined Immune Deficiency (SCID) that makes up the majority of all cases of SCID. This condition mostly affects male infants. Symptoms include extreme susceptibility to viral and bacterial infections, thrush, and failure to thrive. SCID is fatal if not treated. Patients may receive bone marrow transplantation or gene therapy as curative treatment.

Learn more about γc Deficiency X-Linked SCID:

Please note that the information contained on these pages is not intended to provide specific medical advice; rather, it is intended for informational purposes only in order to provide a better understanding of these diseases. Please consult with a qualified physician for diagnosis and answers to your questions.

Glossary

encyclopedia.svgTo help you better understand the medical terminology we have used around the Global Village, we have compiled a list of terms to make it easier for you.

Abscess

A collection of pus in the body that usually causes inflammation and swelling. Abscesses can develop anywhere in the body. They can appear as tender, raised masses. Deep abscesses in the body can cause organ damage.

Adenosine Deaminase

An enzyme produced by the ADA gene, most active in lymphocytes. The purpose of this enzyme is to eliminate deoxyadenosine, which is formed when DNA breaks down and is harmful to lymphocyte function.

Agammaglobulinemia

A Primary Immunodeficiency characterized by the absence of B cells, dysfunction of antibodies, and Btk gene abnormalities. This results in a vulnerable immune system, leaving an afflicted individual more susceptible to infections.

Allele

An allele is 1 of 2 versions of a gene. Individuals inherit 1 allele from each parent. Different alleles are termed heterozygous and are responsible for differences in phenotypes.

Anaphylaxis

A severe allergic reaction to an allergen. After exposure to an allergen, the body releases antihistamine, causing airways to close. The flood of chemicals from the immune system causes symptoms like shock, an instant drop in blood pressure, swelling of the airways, and a skin rash. If not treated immediately, this reaction can be fatal.

Anemia

A condition that causes a lack of healthy red blood cells that would normally provide enough oxygen to the body’s tissue. This condition ranges in severity and is not always permanent. Symptoms include feelings of fatigue, irregular heartbeat, pale skin, shortness of breath, chest pains, and headache.

Antibody

Also known as immunoglobulins, this protective protein is produced by the white blood cell known as a B cell or B lymphocyte. This immune function is produced as soon as an antigen enters the body. When the immune system lacks these proteins, the afflicted individual is very susceptible to infection.

Antigen

An antigen is a foreign substance or toxin that, upon entry to the body, causes the immune system to produce antibody. Antigens include bacteria, viruses, parasites, fungi, etcetera.

Antigen-Presenting Cell

A type of cell that displays antigen, which is recognized by T cells. Antigen-presenting cells are part of the major histocompatibility complex (MHC). Antigen-presenting cells include dendritic cells, macrophages, and certain B cells and epithelial cells.

Apoptosis

Programmed cell death that occurs normally to remove cells that are unwanted or damaged. This process is essential to maintaining the health of the body. If this process is irregular, it can be the cause of many different diseases (e.g. tumor growth).

Autoantibodies

An antibody that attacks self-antigens of the body. Autoantibodies are harmful and can cause damage to cells and tissues.

Autoimmunity

The failure of the immune system to recognize “self” components, leading to attacks of its own cells and tissues. Autoimmunity can cause diseases such as Celiac Disease, Graves’ Disease, and Diabetes Mellitus Type 1, amongst others.

Autoinflammatory Diseases

Characterized by intense, prolonged periods of inflammation, including symptoms such as fever, swelling, edema, and development of rashes. This category of diseases is caused by deficiencies in the innate immune system, which react to cause inflammation without being exposed to antigens or autoantibodies.

Autosomal Dominant

A pattern of genetic inheritance in which only 1 copy of a gene is needed in order for a certain phenotype to be expressed. Genes of the 22 pairs of autosomes (non-sex chromosomes) can be inherited in dominant patterns.

Autosomal Recessive

A pattern of genetic inheritance in which 2 copies of a gene are needed in order for a certain phenotype to be expressed. Genes of the 22 pairs of autosomes (non-sex chromosomes) can be inherited in recessive patterns.

Basophil

A type of granulocyte that assists in the inflammatory response. Basophils contain histamine that promotes proper blood flow. Additionally, the basophil contains heparin, which helps prevent the blood from clotting too rapidly. Basophils can bind IgE, and play an important role in allergies and parasitic infection.

B Cell

A type of lymphocyte, or white blood cell, that produces antibodies. The B cell is a vital part of the immune system. B cells are an important component of humoral immunity within the adaptive immune system. B cells produce antigen-specific antibodies. Through cell differentiation, the B cell can either become a plasma B cell or a memory B cell.

Blood Plasma

The pale yellow liquid component of blood that contains red and white blood cells in suspension. Plasma transports blood cells, nutrients, antibodies, proteins, and chemical messengers throughout the body to maintain proper function and fluid balance. Plasma plays an essential role in protecting from infection.

Bone Marrow Transplant

A procedure to replace damaged or broken-down bone marrow located in healthy tissue. Bone marrow is the soft tissue found inside our bones. There are 3 types of bone marrow transplants—autologous, allogenic, and umbilical cord blood.

Candidiasis

A fungal infection caused by a species of Candida yeast. Candidiasis can affect different parts of the body. Some examples include the mouth and throat (thrush), vagina (yeast infection), or the bloodstream.

Carrier

An individual with 1 recessive, abnormal copy of an allele and a normal, healthy copy on the same locus of a pair of chromosomes. Carriers have the capability to pass an abnormal copy on to offspring. Depending on inheritance from the other parent, a disease phenotype may be expressed.

Cell Differentiation

The process in which a cell develops into a specific role. During growth and development, each cell is programmed or given a specific role in the body. Cell differentiation is important to the development of cell function and function of the organism.

Cell-Mediated Immune Response

An immune response that occurs when T cells attack foreign antigens through cytotoxicity, activation of macrophages, or production of lymphokines.

Chromosome

A strand of tightly coiled DNA and proteins that contain hereditary information (genes), which provides instructions for gene expression. Each chromosome contains a centromere (constriction point), 2 short arms (p arm), and 2 long arms (q arm).

Complement System

A part of the immune system that is composed of many plasma proteins that cause an inflammatory response to fight infection. This system “complements” antibodies and phagocytes by assisting in clearing pathogens.

Consanguinity

Relationship by blood or kinship. This term specifically refers to mating of 2 individuals with 1 or more recent ancestors in common.

Cord Blood

Blood contained in a newborn’s umbilical cord, which contains stem cells that can renew themselves. Cord blood can be used to strengthen the immune system and replace damaged cells.

Cytokine

A group of proteins, gloproteins, and peptides that provide regulatory and signaling functions. They help to regulate host defense mechanisms in response to infection, inflammation, or trauma to the body. Interferon and interleukins are examples of cytokines.

Cytotoxicity

The level to which an agent has the potential to cause harmful, destructive action on a cell. Examples of cytotoxic agents include autoantibodies and venom.

Dendritic Cells

Antigen-presenting leukocytes typically found in tissue that has direct interaction with the external environment like the skin, inner lining of the nose, stomach, and lungs. The primary function of this immune cell is to assess entering antigens and let the other immune cells, B cells, and T cells know about the danger and how to formulate an attack. It is the primary messenger between the innate and adaptive immune systems.

DNA

The study of genetics starts with understanding DNA, which is short for deoxyribonucleic acid. DNA is the code in our cells that determines how our bodies develop and function. DNA is a complicated structure. It is helpful to think about DNA as really long ladder-like chains that coil around on themselves. Each step in the ladder consists of pieces we call bases. There are only four bases in all of our DNA. These are represented by the letters A, C, G, & T. These four bases are repeated in different sequences throughout the DNA ladder. Specific sections of bases of DNA are GENES.

Eczema

An inflammatory skin reaction that presents itself as bumps, redness, swelling, and scaling. It is a rather common problem in many individuals; however, it can be more severe in an immunodeficient patient.

Edema

Swelling of the skin caused by excess fluid found in your tissue. This can affect any part of the body; however, it usually presents itself on the hands, arms, feet, ankles, and legs. Causes range from medication, pregnancy, and a possible underlying disease like heart failure or kidney disease.

Enzyme Replacement Therapy

A medical therapy in which old, defective, or absent enzymes are replaced through regular infusions.

Eosinophil

A type of granulocyte formed in the bone marrow. It contains cytoplasm filled with granules that contain proteins and enzymes. Eosinophils are present in the inflammatory response, trapping and killing foreign substances. They may also play a role in gland development. Overactivity of eosinophils can be harmful to the body.

Epidemiology

The study of the patterns, distribution, and causes of diseases as they appear in different populations, and with the goal to assist affected populations and identify future prevention methods.

Erythrocyte

A red blood cell, the most common type of cell, that transports oxygen and carbon dioxide throughout the body, to and from tissues. Red blood cells also contain hemoglobin, which presents red pigmentation.

Family History

A record of health information about an individual and his or her family members. Based on what close kin have been diagnosed with in the past, physicians analyze patterns, giving them the ability to not only assess the individual’s risk factor for certain diseases, but to also predict the possibility of a disease for the individual’s future generations.

Gamete

A mature sex cell, such as a sperm or egg, which contains a haploid number of chromosomes and is capable of fusing with another sex cell.

Gene Expression

The manifestation of a phenotype attributed to a specific gene through transcription and genetic translation.

Gene Mutation

An alteration in the DNA sequence that composes a gene, sometimes causing disease. Mutations can be inherited or acquired throughout the lifespan. Genetic mutations can be categorized as missense, nonsense, insertion, deletion, duplication, frameshift, or repeat expansion.

Gene Regulation

The process in which genes are turned on and off. This is important in an organism’s development stages as the proper genes are expressed at the appropriate time.

Genes

A single gene may be anywhere from several hundred DNA bases long to more than 2 million bases long! Humans have somewhere around 20,000 to 25,000 genes. Each gene contains a code that gives instructions on how to make a protein or enzyme that our bodies need to develop and work correctly. These proteins and enzymes in turn are the building blocks of our bodies. They make muscle, tissue, and hair and carry messages within our body. They are the catalyst for millions of reactions that occur every single minute in a living human.

Gene Therapy

A type of medical treatment that uses genes as a method to treat disease. Researchers are approaching this type of therapy in a variety of different ways, such as replacing a mutated gene with a new gene, inactivating a mutated gene that is not functioning properly, and introducing a new gene in order to fight disease.

Genetic Variants

The phenotypic and genotypic differences among individuals and populations.

Genotype-Phenotype Correlation

An association that refers to the resulting phenotype as a result of the presence of a mutation in the genotype.

Graft-versus-Host Disease

This is a reaction that can occur because of newly injected stem cells and, sometimes, transplanted organs that attack the patient’s tissue and antigen-attacking cells.

Granulocyte

White blood cell made up of small granules that contain proteins. The 3 types of granulocytes are called neutrophils, eosinophils, and basophils. The function of a granulocyte is to fight off antigens. Individuals who do not produce enough of this white blood cell are more prone to infection.

Granuloma

An area of inflammation in tissues caused by an accumulation of macrophages, usually due to infection.

Haplo

A term meaning simple or single. Haplo refers to haplogroups studied through maternal and paternal lines of inheritance in the mitochondria and Y-chromosome, as there is very little recombination that occurs in these lines.

Hematopoietic Stem Cell Transplant

A medical therapy that includes the infusion of stem cells derived from bone marrow, cord blood, or peripheral blood to replace and restore function in patients who have immune deficiencies.

Hemolysis

The breakdown of red blood cells resulting in the release of hemoglobin and cytoplasm into the blood plasma.

Heritability

The proportion of variability of a particular phenotype inherited through genes.

Heterogeneous

Consisting of different genes. A Heterogenous Condition is caused by a variety of different genes or alleles.

Homogeneous

Consisting of the same genetic components. A Homogenous Condition is caused by inheritance of the same molecular defect, or the inheritance of several mutations affecting the same gene.

Host Defense Mechanisms

Defenses that protect against infection, including natural barriers (skin, mucous membranes, the respiratory tract, gastrointestinal tract, and genitourinary tract), non-specific immune responses (macrophage, lymphocyte, cytokine activation, the inflammatory response), and specific immune responses (activation of the complement system).

Humoral Immune System

Also known as the antibody-mediated system because of the active function of antibodies. In this system, macrophages first ingest pathogens and then present components of engulfed material, which trigger helper T cells. These cells help to trigger B cells, which begin to produce antibodies that bind to foreign antigens. Antibodies produce “memory” of antigens to help quickly respond to the same antigen encountered again.

Hypoplasia

Underdevelopment or incomplete development of an organ or tissues that is often the result of inadequate cell production.

Immunoglobulins

A term for antibodies, these Y-shaped glycoprotein molecules are produced by B cells to recognize and bind to specific antigens. Immunoglobulins are produced in 5 different varieties: IgA, IgD, IgG, IgE, and IgM.

Inflammatory Bowel Disease

Characterized by chronic inflammation of the gastrointestinal tract, causing abdominal discomfort and pain. Specific conditions include Crohn’s Disease and Ulcerative Colitis.

Innate Immune System

A non-specific portion of the immune system that provides the first line of defense against harmful pathogens. This system relies on anatomical barriers (skin, epithelial surfaces, sweat, cilia, surfactant), humoral barriers (edema, phagocytosis, lysis, opsonization), and cellular barriers (macrophages, Natural Killer cells, neutrophils, and eosinophils).

Interleukin

Cytokines (proteins) that stimulate and mediate the activity of lymphocytes such as T cells and B cells.

Intravenous Immunoglobulin

A product containing pooled immunoglobulin from approximately 1,000 blood donors administered intravenously to patients with deficiencies in immunity.

Isohemagglutinin

An antibody that causes the agglutination of red blood cells, which develops the main blood groups. Examples include anti-A and anti-B isohemagglutinins.

Isotype Switching

A process that is a result of deletion of DNA sequences, allowing antibodies to switch from IgG and IgM to either IgE, IgA, or IgG. This process occurs during B-cell differentiation into plasma cells and is mediated by V(D)J recombinase.

Leukocyte

Another term for a white blood cell that circulates in the blood and lymph, and is comprised of B cells, T cells, granulocytes, monocytes, and macrophages.

Ligand

A substance that binds to a biomolecule, usually a protein. Ligands are often signal-triggering molecules that cause biochemical changes. Ligands may be activators, inhibitors, neurotransmitters, or substrates.

Lymphoproliferation

The production of excessive quantities of lymphocytes, often associated with autoimmune syndromes and caused by mutations in the FAS gene.

Macrophage

A white blood cell that interacts in the innate and adaptive immune systems, engulfing and digesting pathogens that enter the body.

Major Histocompatibility Complex

Cell surface molecules that mediate the interaction of white blood cells with other cells in the immune system. There are 3 different classes of MHC. Class I is associated with CD8, allowing destruction of host cells that display foreign antigen. MHC Class II is associated with specific immunity, moderating CD4-dependent responses to antigen.

Matched Related Donor

A type of bone marrow transplant in which the donor is human leukocyte antigen (HLA) identical to the recipient. The donor and recipient are usually related through common kinship (sibling, parents, or other relatives). This type of transplant is least likely to cause Graft-versus-Host Disease.

Matched Unrelated Donor

A type of bone marrow transplant in which the donor and recipient have identically matched human leukocyte antigens. Unlike a matched related donor transplant, the donor and recipient do not share a common recent relative or kinship.

Mismatched Unrelated Donor

A type of bone marrow transplant in which the donor and recipient have 5 out of 6 matched human leukocyte antigens. This type of transplant may be used if a matched related or unrelated donor is not available. The donor and recipient do not share a common recent relative or kinship.

Mitochondria

Cells that produce energy for the body to carry out cellular functions. Specifically, mitochondria control ATP production. Mitochondria are inherited maternally.

Molecular Sequencing

The process of determining the order of DNA molecules (adenine, cytosine, guanine, thymine) of individual genes, gene clusters, chromosomes, or the entire genome. Sequencing can provide information on mutations in genes and underlying mechanisms of genetic disorders.

Natural Killer Cell

A type of lymphocyte of the innate immune system that serves important roles in host defense mechanisms. These cells provide surveillance, and help to reject virally infected cells and tumor cells. Natural Killer (NK) cells contribute to co-stimulation of immune cells, production of cytokines, and signaling of cytotoxic cell activity.

Neutropenia

An abnormally low count of neutrophils leading to higher susceptibility to infection. This condition is defined as fewer than 1,700 neutrophils per microliter.

Neutrophil

A type of granulocyte that has high phagocytic activity, engulfing harmful bacteria and microorganisms that enter the body. This white blood cell helps to mediate immune responses, and migrates to areas of infection through chemotaxis.

Newborn Screening

A process that identifies severe medical conditions that can affect long-term health and survival. At birth, drops of blood are collected from pricking a newborn’s heel for the purpose of testing for genetic, metabolic, and/or endocrine disorders that can be detected through developed assays. Conditions identified early can be properly diagnosed and treated to prevent morbidities or even death that may occur otherwise.

Passive Immunity

Immunity acquired from another individual through the transfer of antibodies. This can refer to antibodies passed naturally from mother to offspring, or artificially through injection of antibodies.

Pathogen

Any agent that can cause disease. Most commonly a pathogen refers to bacteria, virus, fungi, or parasite.

Phagocyte

White blood cells that engulf harmful pathogens that enter the body, or any dead or decaying cells.

Phagocytosis

The process in which a phagocyte engulfs and digests a harmful pathogen, or dead or decaying cellular material.

Pharyngeal

Relating to or located in the pharynx (mouth, throat), which is posterior to the nasal cavity and superior to the esophagus.

Recombination

The exchange of DNA during meiosis between 2 homologous chromosomes to provide genetic variety in offspring.

Recurrent Infections

A breakdown in the body’s immune defense, causing abnormally frequent illness. Recurrent infections may be due to an overactive (allergies) or underactive immune system (Primary Immunodeficiency).

Septicemia

A serious, life-threatening infection that can affect all body systems. Symptoms include body chills, high fever, rapid heartbeat, and can progress quickly.

Sex-Linked

The phenotypic expression of genetic material that is located on or linked to a sex chromosome (X or Y).

Signaling

Communication between cells to activate and coordinate function. Signaling plays an important role in cell development, immunity, tissue repair, and normal function. Errors in cell signaling can result in abnormal function, causing disease.

Sinopulmonary

Affecting, relating to, or involving the nasal sinuses and the airway of the lungs.

Sinusitis

Swelling or inflammation of the tissue in the sinuses, which causes susceptibility to bacterial, fungal, or viral growth. Common conditions include Allergic Rhinitis, the Common Cold, and Nasal Polyps.

Somatic Cell

A type of cell that forms a multicellular organism and contains chromosomes. Somatic cells are not gametes, germ cells, or stem cells. Somatic cells compose blood, bones, connective tissue, internal organs, and skin.

Stem Cell

A biological cell that can divide to create additional stem cells and differentiate into a specialized cell. There are 2 types of stem cells: embryonic and adult. Stem cells have restorative and regenerative function.

Subcutaneous Immunoglobulin

A product containing pooled immunoglobulin from approximately 1,000 blood donors administered under the skin in fatty tissues of the abdomen, lower back, thighs, and upper arms to patients with deficiencies in immunity. Subcutaneous Immunoglobulin infusions are typically administered at home and more frequently; biweekly, weekly, and even daily based on a patient's need.

T Cell

A lymphocyte, or white blood cell, that matures in the thymus, contains a distinct T-cell receptor, and plays an essential role in cell-mediated immune function. There are several types of T cells including cytotoxic, helper, memory, natural killer, and regulatory T cells.

T-Cell Receptor Excision Circles (TREC)

A byproduct of DNA produced during the rearrangement of T-cell receptor (TCR) genes. An analysis of TREC can determine thymic function and competency of the T-cell effector immune response.

Thrombocytopenia

A condition characterized by an abnormally low amount of platelets, which help the blood to clot. This condition can be present in bone marrow, the bloodstream, or the liver or spleen.

Thrush

A condition that occurs when a fungus, known as Candida, grows abnormally in the mouth and throat. Symptoms appear as large white sores that may bleed in the mouth or on the tongue. Long-lasting thrush can signify weakness or dysfunction of the immune system.

Thymus

An organ of the immune system where T cells are produced and matured. The thymus is located behind the sternum, in front of the heart. It is distinguished by 2 identical lobes.

Thymus Transplantation

An organ transplant, in which the thymus is removed and replaced with a donated matched thymus. Individuals with DiGeorge Syndrome, characterized by absent thymus or hypoplasia of the thymus, require transplantation.

V(D)J Recombination

Genetic recombination of immunoglobulin and T-cell receptors to provide diversity of the immune system and to encode proteins to provide defense against bacteria, viruses, parasites, and other harmful antigens. Variable, Diverse, and Joining segments refers to the random process of selection to create this gene diversity.

Whole Exome Sequencing

Whole Exome Sequencing is a genetic testing technique that zeroes in on the protein-coding portion or exons of the genome.

Whole Genome Sequencing

A type of DNA sequencing that provides complete and comprehensive information about the genome. Also known as entire genome sequencing, this process allows sequencing of all of an organisms’ chromosomes, providing specific information on the 6 billion nucleotides that comprise human DNA. Whole genome sequencing provides distinct and vast amounts of information that can be used to analyze underlying disease mechanisms.

X-Linked Recessive

A type of pattern inheritance in which a gene is passed on through the X-chromosome. A mutation on the X chromosome will cause the phenotype to be expressed in male individuals, since they only carry one X chromosome. Females are more common carriers; however, if they inherit the same mutation on the X chromosome from both parents, they will express the phenotype.

Citations

  1. PubMed
  2. National Institutes of Health
  3. Merriam-Webster's Medical Dictionary
  4. Ochs HD, C.I. Smith E, Puck JM, eds. Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. 3d ed. New York, NY: Oxford University Press; 2007.
  5. Ochs HD, C.I. Smith E, Puck JM, eds. Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. New York, NY: Oxford University Press; 1999.
Please note that the information contained on these pages is not intended to provide specific medical advice; rather, it is intended for informational purposes only in order to provide a better understanding of these diseases. Please consult with a qualified physician for diagnosis and answers to your questions.

FAQs

questionmarks.svgDo you have questions about Primary Immunodeficiency? If you or someone you know is affected by Primary Immunodeficiency or has been recently diagnosed, we can provide some answers for you. We understand it can be overwhelming and complex. That is why we have compiled a list of Frequently Asked Questions to better answer the unknowns you may have at this time.

To get started, choose from one of the questions below:

What is Primary Immunodeficiency?

Primary Immunodeficiencies (PI) are a group of more than 450 disorders of the immune system with varying degrees of severity. They occur when one or more essential parts of the immune system do not work correctly. Primary Immunodeficiency often presents itself in the form of "ordinary" infections. Physicians sometimes treat the infections while missing the underlying cause, allowing the illnesses to recur, and leaving the patient vulnerable to vital organ damage, physical disability, and even death. Families struggling with Primary Immunodeficiency often do not know where to turn for help. Social, emotional, and financial burdens can often be overwhelming. The problems presented in Primary Immunodeficiency have challenged researchers and immunologists to reach improved diagnoses, treatments, and new therapies. 

What are the signs and symptoms of having a Primary Immunodeficiency?

There are a number of different signs and symptoms of Primary Immunodeficiency. Although it varies somewhat from individual to individual and disorder to disorder, there are some signs and symptoms that occur commonly in many of the disorders.

Perhaps the most common problem that patients with a Primary Immunodeficiency have is increased susceptibility to infection. Primary Immunodeficiency patients have too many, and often recurrent, infections. They may have recurrent and repeated ear infections, pneumonia, bronchitis, sinusitis, or skin infections.

Although less common, immunodeficient patients may have abscesses of their internal organs, such as the liver, or infections of their blood; however, the common theme is that they have more infections than they or their doctor believe is appropriate.

Not every patient with a Primary Immunodeficiency presents with recurrent infections. In some patients, the first infection is serious enough to render the possibility of a Primary Immunodeficiency. Moreover, there are certain infections caused by pathogens that only afflict Primary Immunodeficiency patients. Therefore, the type of infection itself may serve as a red flag for a Primary Immunodeficiency.

Patients with Primary Immunodeficiency may also present with a variety of autoimmune or rheumatologic problems. Furthermore, gastrointestinal (digestive) problems may occur in some patients with a Primary Immunodeficiency. Patients may have excessive cramping, loss of appetite, nausea, and diarrhea. In some patients, the gastrointestinal problems can be the result of an infection of the intestines; in others, they may be a reflection of an autoimmune or Primary Immunodeficiency.

How can Primary Immunodeficiencies be treated?

Once a diagnosis is established, much can be done for immunodeficient patients. At a minimum, the recurring infections can be treated with low or moderate doses of appropriate antibiotics. These can help prevent permanent damage to the lungs and bronchial tubes, thus promoting the patient's long-term survival while improving their quality of life. When appropriate, immunoglobulin therapy is the accepted protocol for a wide range of Primary Immunodeficiencies. Advanced treatments such as the interleukins, PEG-ADA, and gamma interferon can help in some complex cases. Bone marrow transplantation and gene therapy may be the appropriate protocol for specific disorders.

What is it like to live with Primary Immunodeficiency?

There has never been more hope for people who are immunodeficient. All the same, families struggling with any Primary Immunodeficiency face a number of difficulties. For instance, the patient may have long periods of normal health, then suddenly be struck by high fevers, pneumonia, or any of the other problems noted above. 

Lack of public awareness of Primary Immunodeficiency can make the family feel isolated in its attempts to cope. Until recently, public sources of information have been scarce, even for doctors. Also, many patients and parents find they cannot get teachers, principals, employers, and others to understand the nature of the medical problem at hand. 

What does the Jeffrey Modell Foundation do?

The Jeffrey Modell Foundation works tirelessly to create a world in which there are cures for Primary Immunodeficiency (PI) by advocating on behalf of patients and families, ensuring access to the best care, and supporting research efforts. Our main goal is earliest possible diagnosis through global newborn screening to save lives.

Advocacy is at the core of our mission. The Foundation engages with world renowned thought leaders in public policy and immunology and has developed strategic partnerships throughout our thirty-five years of operation to forward our mission, involving governmental bodies in addition to lay, scientific, and medical communities.

The Foundation strives to make a difference in the lives of patients and families living with PI, and is committed to turn pain, despair, and suffering into comfort, hope, and health. Our “Roots & Wings” program provides travel support for critically ill children requiring lifesaving treatment.

In 2004, JMF initiated the first national PSA campaign about PI. The “When I Grow Up” campaign resulted in a tenfold increase in the reported number of patients identified, diagnosed and treated.

The Jeffrey Modell Centers Network was created to meet the rising need for referrals, diagnosis, and treatment at specialized centers for patients with PI. The JMCN serves as a global resource for the dissemination of information and education about PI.

These programs, and many more, are part of our ongoing efforts to better understand, diagnose, and treat PI around the world.

Why is it that physicians don't always seem aware of these immune defects?

In the last 30+ years, it has become clear that immune defects are more common than originally thought. In the United States, most specialists who see and treat patients with congenital immune defects are pediatricians, and many physicians are not aware that adults may be found who have these defects, not just infants and children.

Is antibody deficiency the same as AIDS?

NO. Acquired Immune Deficiency Syndrome (AIDS) is a widespread disruption of the immune system caused by a specific viral infection known as human immunodeficiency virus (HIV). Primary antibody deficiencies (and most secondary antibody deficiencies) are not contagious and do not present any risk to other people. In fact, healthy people carrying infections pose a threat to people with antibody deficiencies because those with deficiencies are so vulnerable to infections.

What are the symptoms of antibody deficiencies?

Antibody deficiencies limit the ability of the immune system to recognize and respond to infections caused by bacteria, viruses, or other pathogens. A patient with an antibody deficiency will, therefore, tend to have both more frequent and more severe infections, and infections will often be of longer duration. These patients are also less capable of “developing immunity,” and as a result, often suffer from chronic and recurring infections.

How can a doctor confirm a diagnosis of antibody deficiency?

When it is suspected that a patient's immune system is not working properly, the physician can run a set of laboratory tests to confirm the diagnosis. For most people, all that is required is a blood sample and a vaccination test, then a second blood test 2 to 3 weeks later. Examination of the first blood sample will determine whether any of the cells needed to complete immune response are missing and whether antibodies are present in adequate amounts. 

The vaccination and second blood test are performed to determine if functioning antibodies are being produced by the body against specific organisms. The vaccination introduces a noninfectious foreign protein to the immune system. When the second blood test is done at the return visit, it should reveal the presence of antibodies created specifically to fight against the test protein. A lack of specific antibodies demonstrates an inability to mount an effective defense against infections.

Is IVIG therapy successful?

YES. IVIG infusions help to restore the missing antibody protection against infections, allowing the patient to lead a normal life. 

Since a normal life does involve getting sick sometimes, patients receiving IVIG therapy may still have an occasional cold or infection that needs treatment with antibiotics. However, they will have far fewer, milder, and more controllable infections than they had before starting IVIG therapy. This means that they will be able to lead more active, less restricted lives. 

Are there different kinds of IVIG products, and how is it determined what type you get?

There are several different IVIG products on the market. All are > 95% IgG, the main serum protein that contains protective antibodies. They differ from each other in strength, bottle size, storage (some are liquid, some are a powder that has to be reconstituted), excipients (substances added to the IgG such as sugar or albumin to stabilize the product), manufacturing, and viral inactivation methods. 

All should be free of Hepatitis C and HIV and other pathogens, which is accomplished during the manufacturing process. All of the products have protective antibodies against common viruses and bacteria. Thus, all are of value in the treatment of primary antibody immunodeficiencies. 

Some products are lower in IgA, a minor immune globulin that may sensitize individuals who lack serum IgA but can make antibody to the infused IgA. For a patient with a selective IgA deficiency who needs IVIG (most do not need it), such products may be preferred.

Are there side effects with IVIG therapy?

Therapy is safe, but some patients can experience side effects, such as fever, chills, rash, headaches, muscle aches, or abdominal pain. These side effects resemble flu symptoms, and many can be reduced by slowing the rate of infusion or by taking analgesics like aspirin, ibuprofen, or acetaminophen.

What is an antibody deficiency?

An antibody deficiency is an immune defect that limits the body’s ability to identify “foreign invaders” or pathogens. 

In a fully functional immune system, specialized cells produce antibodies, which contribute to immune defenses by binding to the invading cell or particle, identifying it for destruction. In patients with antibody deficiency, these specialized proteins may be missing, not working properly, or too few in number to be effective. 

Antibody deficiencies are classified as either “primary” or “secondary.” Primary antibody deficiencies arise spontaneously from genetic errors and other mechanisms that are only partially understood. Primary antibody deficiencies can either involve all antibodies or be limited to specific types of antibodies. 

If Primary Immunodeficiency diseases are genetic or congenital, why is it that some of these defects are diagnosed in adults?

It is possible that these defects are present all along, but not diagnosed due to compensating immune functions that keep serious problems from developing earlier. It is also possible that there is a slowly deteriorating immune function, genetically determined, that does not become significant until later in life.

Can diet help fight infections?

YES. Good nutrition gives the body the energy and the resources to fight infections. Eating right always makes good sense, and families with antibody deficiencies should take extra care to maintain a healthy and balanced diet.

Can antibody deficiencies be treated?

YES. Many years ago, the only form of active treatment for antibody deficiency was antibiotic therapy, and the only form of prevention was isolation. For children, this meant staying out of school and out of contact with other children and adults. 

Today, however, antibody replacement therapy is available. Because antibodies are also known as immunoglobulins, the term “immunoglobulin therapy” is commonly used. This treatment can be given intravenously (IVIG) or subcutaneously (SCIG). 

IVIG and SCIG therapy replace the antibodies that are missing. The infusion contains antibodies purified from plasma donated by volunteer donors. These antibodies remain in circulation for about a month. 

Jeffrey said that I was like a private investigator, always researching PI. I put every ounce of that knowledge into the Information Booth.
  • Jeffrey said that I was like a private investigator, always researching PI. I put every ounce of that knowledge into the Information Booth.
  • Here you will find the best Expert Immunologists from around the world, as well as detailed FAQs. Now it’s your turn to investigate,
  • you will be motivated by his plea for us to “Do Something!” and that you too, will find inspiration for your own journey!