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

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.

Read the 10 Warning Signs of Primary Immunodeficiency in Over 50 Languages

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.

Learn about Your Immune System

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.

To help you better understand the medical terminology used across our website review or download our Glossary to learn on-the-go.

Types of PI

There are more than 450 unique Primary Immunodeficiency disorders that impact the immune system. To learn more about a specific disorder, click through the definitions below.

Be sure to check out the 10 Warning Signs if you’re experiencing repeated infections. The 10 Warning Signs have also been translated into more than 50 languages.

If you’re a medical professional, you can find the 4 Stages of Testing (algorithm) on our website.

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, 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 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:

http://www.omim.org/entry/602450

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:

http://ghr.nlm.nih.gov/condition/ataxia-telangiectasia

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:

http://ghr.nlm.nih.gov/condition/autoimmune-lymphoproliferative-syndrome

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:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809312/

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:

http://ghr.nlm.nih.gov/condition/cartilage-hair-hypoplasia

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:

http://ghr.nlm.nih.gov/condition/chediak-higashi-syndrome

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:

http://ghr.nlm.nih.gov/condition/chronic-granulomatous-disease

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 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 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:

http://www.mayoclinic.org/common-variable-immunodeficiency/

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:

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:

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:

http://ghr.nlm.nih.gov/condition/hermansky-pudlak-syndrome

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 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:

http://ghr.nlm.nih.gov/condition/x-linked-hyper-igm-syndrome

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:

http://emedicine.medscape.com/article/136471-overview

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:

http://ghr.nlm.nih.gov/condition/x-linked-hyper-igm-syndrome

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:

http://ghr.nlm.nih.gov/condition/immune-dysregulation-polyendocrinopathy-enteropathy-x-linked-syndrome

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 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:

http://emedicine.medscape.com/article/887236-overview

Leukocyte Adhesion Deficiency-I Clinical Features

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:

http://www.ncbi.nlm.nih.gov/pubmed/9012922

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:

http://ghr.nlm.nih.gov/condition/nijmegen-breakage-syndrome

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:

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:

http://my.clevelandclinic.org/orthopaedics-rheumatology/diseases-conditions/periodic-fever-syndrome.aspx

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 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:

http://www.aaaai.org/conditions-and-treatments/primary-immunodeficiency-disease/selective-iga-deficiency.aspx

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:

http://www.ncbi.nlm.nih.gov/books/NBK22254/

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:

http://ghr.nlm.nih.gov/condition/shwachman-diamond-syndrome

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:

https://immunology.org/document.doc?id=688

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:

http://ghr.nlm.nih.gov/condition/tumor-necrosis-factor-receptor-associated-periodic-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:

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:

http://ghr.nlm.nih.gov/condition/wiskott-aldrich-syndrome

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:

http://ghr.nlm.nih.gov/condition/x-linked-agammaglobulinemia

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:

http://ghr.nlm.nih.gov/condition/x-linked-lymphoproliferative-disease

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:

http://ghr.nlm.nih.gov/condition/x-linked-severe-combined-immunodeficiency

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:

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:

http://ghr.nlm.nih.gov/gene/IL2RG

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.

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Glossary

To 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.

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.

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.

Citations

PubMed
National Institutes of Health
Merriam-Webster's Medical Dictionary
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.
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

Do 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:

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Primary Immunodeficiency Resources

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