There are more than 200 different forms of primary immune deficiency diseases (PIDDs). NIAID conducts research across all PIDDs as well as among the individual diseases that make up this broad category. The following are some of the individual PIDDs that NIAID is currently studying.
Autoimmune lymphoproliferative syndrome (ALPS) is a rare immune disorder first described by NIH scientists in the mid-1990s that can cause numerous autoimmune problems, such as low levels of red blood cells, clot-forming platelets, and infection-fighting white blood cells. These problems can increase the risk of infection and hemorrhage. Read more about autoimmune lymphoproliferative syndrome (ALPS).
Autoimmune polyglandular syndrome type 1 (APS-1), also called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), causes a diverse range of symptoms, including autoimmunity against different types of organs and increased susceptibility to candidiasis, a fungal infection caused by Candida yeast. Read more about APS-1 (APECED).
BENTA disease is a rare genetic disorder of the immune system caused by mutations in the gene CARD11. The disease is characterized by high levels of certain immune cells starting in infancy, an enlarged spleen, enlarged lymph nodes, immunodeficiency, and an elevated risk of lymphoma, a type of cancer Read more about BENTA disease.
Caspase Eight Deficiency State (CEDS)
Caspase eight deficiency state, or CEDS, is a very rare genetic disorder of the immune system caused by mutations in the CASP8 gene. CEDS is characterized by an enlarged spleen and lymph nodes, recurrent sinus and lung infections, recurrent viral infections, and a low level of infection-fighting antibodies. NIH researchers first described this condition in two siblings in 2002. Read more about CEDS.
NIAID researchers are studying how CARD9 deficiency and other genetic disorders result in susceptibility to candidiasis, an infection with the yeast fungus Candida. People with CARD9 deficiency are particularly susceptible to Candida infections of the central nervous system. Read more about CARD9 deficiency and other syndromes of susceptibility to candidiasis.
CGD occurs when white blood cells called phagocytes are unable to kill certain bacteria and fungi, making people highly susceptible to some bacterial and fungal infections. Mutations in one of five different genes can cause this disease. Read more about chronic granulomatous disease (CGD).
CVID is caused by a variety of different genetic abnormalities that result in a defect in the capability of immune cells to produce normal amounts of protective antibodies. People with CVID experience frequent bacterial and viral infections of the upper airway, sinuses, and lungs. Read more about common variable immunodeficiency (CVID).
Congenital neutropenia syndromes are a group of disorders present from birth that are characterized by low levels of neutrophils, a type of white blood cell necessary for fighting infections. Read more about congenital neutropenia syndromes.
CTLA4 deficiency is a rare disorder that severely impairs the normal regulation of the immune system, resulting in conditions such as intestinal disease, respiratory infections, autoimmune problems, and enlarged lymph nodes, liver, and spleen. NIAID scientists and their collaborators identified the disease in 2014. Read more about CTLA4 deficiency.
DOCK8 deficiency is a rare immune disorder named after the mutated gene responsible for the disease. NIAID researchers discovered the cause of DOCK8 deficiency in 2009. People with this syndrome have lower-than-normal numbers of immune cells, which have a diminished capacity to move through dense tissues like the skin. These abnormalities lead to recurrent viral infections of the skin and respiratory system. Read more about DOCK8 deficiency.
GATA2 deficiency is a rare disorder of the immune system with wide-ranging effects. First identified in 2011, the disorder is characterized by immunodeficiency, lung disease, problems of the vascular and lymphatic systems and myelodysplastic syndrome (a condition characterized by ineffective blood cell production). Read more about GATA2 deficiency.
Glycosylation refers to the attachment of sugars to proteins, a normal process required for the function of healthy cells. Defects in glycosylation can disrupt the immune system, resulting in immunodeficiency and potentially causing extensive and severe symptoms. Read more about glycosylation disorders with immunodeficiency.
Many different syndromes are known to lead to high levels of an antibody called immunoglobulin E, or IgE. Many more such syndromes likely remain unknown. Collectively, these conditions are called hyper-IgE syndromes, or HIES. Read more about hyper-IgE syndromes (HIES).
Hyper-Immunoglobulin M Syndromes
Hyper-immunoglobulin M (IgM) syndromes are rare, inherited conditions in which the immune system fails to produce normal levels of the antibodies IgA, IgG and IgE but can produce normal or elevated levels of IgM. Various gene defects that impair communication between T cells and antibody-producing B cells can lead to hyper-IgM syndromes. Hyper-IgM syndromes can cause severe respiratory infections in infancy and a higher risk of rare infections throughout life. Treatment includes regular intravenous or subcutaneous antibody replacement therapy, anti-fungal prophylactics, and in some cases, bone marrow transplant from a healthy donor.
Interferon Gamma, Interleukin 12 and Interleukin 23 Deficiencies
Interferon gamma, interleukin 12 and interleukin 23 deficiencies are rare, inherited immune disorders in which the body fails to produce one or more of these signaling molecules, which allow infection-fighting immune cells to communicate. Deficiencies in these molecules lead to increased susceptibility to bacterial and viral infections. Many people with these deficiencies develop granulomas, or inflammatory lesions that form in tissues and organs because of recurring infections. While many of these deficiencies begin to cause symptoms in infancy or childhood, some symptoms appear later in life. Treatment includes antibiotic therapy to prevent infections and, in some cases, bone marrow transplant from a healthy donor.
Leukocyte Adhesion Deficiency (LAD)
Leukocyte adhesion deficiency (LAD) is a rare, inherited immune disorder in which immune cells called phagocytes are unable to move to the site of an infection to fight off invading pathogens. People with LAD experience recurrent, life-threatening infections and poor wound healing. LAD is caused by a mutation in the gene ITGB2, which provides instructions for the phagocyte surface molecule CD18. Treatments for LAD include antibiotics to prevent and treat infection and, in some cases, bone marrow transplants from a healthy donor.
LRBA deficiency is a rare genetic disorder of the immune system caused by mutations in the LRBA gene. This disease impairs normal immune system function and results in autoimmunity, recurrent infections and an increased risk of lymphoma, a type of cancer. People with LRBA deficiency have excessive numbers of immune cells called lymphocytes, which sometimes enter and accumulate in organs where lymphocytes typically are not present in large numbers such as the gut, lungs and brain. This can cause a variety of symptoms. Read more about LRBA deficiency (fact sheet).
PI3 Kinase disease is caused by genetic mutations that overactivate an important immune-system signaling pathway. This causes a chain reaction of problems, disrupting the normal development of infection-fighting B and T cells. People with the disease have a weakened immune system and experience frequent bacterial and viral infections. Read more about PI3 kinase disease.
PLAID and PLAID-like diseases are rare immune disorders with overlapping features, and an allergic response to cold, called cold urticaria, is the most distinct symptom. Read more about PLCG2-associated antibody deficiency and immune dysregulation (PLAID).
SCID is a group of rare, life-threatening disorders caused by mutations in different genes involved in the development and function of infection-fighting T and B cells. Infants with SCID appear healthy at birth but are highly susceptible to severe infections. Read more about severe combined immunodeficiency (SCID).
STAT3 dominant-negative disease (STAT3DN)—also known as autosomal dominant hyper-IgE syndrome (AD-HIES) or Job’s Syndrome—results from mutations in the gene that encodes a signaling protein called STAT3. People with this disease tend to have very high levels of an antibody called immunoglobulin E (IgE), recurrent infections of the skin and lungs, recurrent bone fractures, unusually flexible joints, and inflamed skin. Read more about STAT3 dominant-negative disease.
STAT3 Gain-of-Function Disease
STAT3 gain-of-function disease is a rare genetic disorder of the immune system caused by a malfunction in the STAT3 gene that leads to overactive STAT3 protein. Symptoms of this disease begin early in life and include swelling of the lymph nodes, low blood cell counts, and autoimmunity that can affect multiple organs and tissues. People with STAT3 gain-of-function disease may experience recurrent infections, eczema, and growth problems. Read more about STAT3 gain-of-function disease.
People with WHIM syndrome have low levels of infection-fighting white blood cells, especially neutrophils, predisposing them to frequent infections and persistent warts. Read more about WHIM Syndrome (WHIMS).
Wiskott-Aldrich Syndrome (WAS)
Wiskott-Aldrich syndrome (WAS) is a rare genetic disorder of the immune system that primarily affects boys. WAS is an X-linked recessive disease caused by mutations in the WAS gene, which provides instructions for production of Wiskott-Aldrich syndrome protein. The disorder is characterized by abnormal immune function and a reduced ability to form blood clots. This can result in prolonged episodes of bleeding, recurrent bacterial and fungal infections, and increased risk of cancers and autoimmune diseases. Read more about WAS.
XLA is caused by an inability to produce B cells or immunoglobulins (antibodies), which are made by B cells. People with XLA develop frequent infections of the ears, throat, lungs, and sinuses. Read more about X-linked agammaglobulinemia (XLA).
XLP primarily affects boys and is characterized by a life-long vulnerability to Epstein-Barr virus (EBV), a common type of herpesvirus. People with XLP are healthy until they are exposed to EBV. Then, they can become seriously ill and experience swollen lymph nodes, an enlarged liver and spleen, hepatitis and lymphoma, a type of cancer. Read more about X-linked lymphoproliferative disease (XLP).
XMEN disease is a rare genetic disorder of the immune system. It is characterized by low levels of infection-fighting CD4+ cells, chronic Epstein-Barr virus (EBV) infection, and EBV-related lymphoproliferative disease, in which excessive numbers of immune cells are produced. NIH investigators first described XMEN disease in 2011. Read more about XMEN Disease and watch a video about how NIH scientists discovered the disease.