CTLA4 deficiency is a disease that causes the immune system to attack the body. It is rare and was identified as recently as 2014, but it is severe when it occurs in humans. CTLA4 is a gene that makes the CTL4 protein that works to regulate the immune system. Research shows that CTL4 helps our immune system tell the difference between foreign objects like viruses and bacteria and our own tissues. Only one of the CTLA4 genes makes CTL4 in a person with CTLA4 deficiency. That is a big enough lack of CTL4 protein to cause the immune system to attack several organs, including the kidneys, lungs, digestive system, liver, and nervous system.
Additionally, CTLA4 deficiency causes a lack of B cells and a lack of function in T cells, two different types of white blood cells that help defend the body. CTLA4 is known as a primary immune deficiency disease (PIDD), a genetic disease that affects the function of the immune system. All PIDDs are rare and occur in varying degrees of severity in different people.
Symptoms of CTLA4 deficiency include:
Autoimmune Lymphoproliferative Syndrome (ALPS)
Caspase Eight Deficiency State (CEDS)
CARD9 Deficiency And Other Syndromes Of Susceptibility To Candidiasis
Chronic Granulomatous Disease (CGD)
Common Variable Immunodeficiency (CVID)
Congenital Neutropenia Syndromes
Hyper-Immunoglobulin E Syndromes
Hyper-Immunoglobulin M Syndromes
Interferon Gamma, Interleukin 12 And Interleukin 23 Deficiencies
Leukocyte Adhesion Deficiency (LAD)
PLCG2-Associated Antibody Deficiency And Immune Dysregulation (PLAID)
Severe Combined Immunodeficiency (SCID)
STAT3 Dominant Negative Disease (STAT3DN)
STAT3 Gain-Of-Function Disease (STAT3 GOF)
Warts, Hypogammaglobulinemia, Infections, And Myelokathexis (WHIM) Syndrome
Wiskott-Aldrich Syndrome (WAS)
X-Linked Agammaglobulinemia (XLA)
X-Linked Lymphoproliferative Disease (XLP)
Immunodeficiency Disease Medications
CTLA4 deficiency is caused by a genetic change in the CTLA4 gene. The CTLA4 gene produces the CTL4 protein. Each person inherits one copy of the CTLA4 gene from their mother and one copy from their father. This change, or mutation, causes one copy of the gene to produce less or no CLT4 protein, or to produce CTL4 protein that is non-functional.
Every person with CTLA4 deficiency has one functional CTLA4 gene – there are no documented cases of a human living with two mutated CTLA4 genes, and research on mice shows it is probably a lethal mutation. However, one functional gene is not enough to keep someone from developing a severe immune reaction to the lack of CTL4 protein.
The risk factor for CTLA4 deficiency is having a parent with CTLA4 deficiency. The mutation can be passed on from a parent or arise by itself.
Your doctor may suspect CTLA deficiency if you have any of the symptoms above. They can order lab tests to look at your blood cell count and examine any abnormalities. Many people with a PIDD like CTLA4 deficiency will have a lot of autoantibodies, proteins that are produced in response to the immune system thinking that certain tissues in the body are foreign and should be attacked. In addition to labs, your doctor may take a biopsy of some of your tissues that have been affected to look for high white blood cell count in those tissues. A definitive diagnosis can be made with a genetic test.
Complications of CTLA4 deficiency include:
Treatment for CTLA4 deficiency varies based on how severe the symptoms are. Options include antibody replacement therapy for people who experience frequent infections and do not have enough antibodies, a specialised immune protein, to fight them. Preventative antibiotics, drugs to suppress the immune system’s attack on the body, and bone marrow transplants are all treatment options as well. Bone marrow is where white blood cells are made.
Someone living with CTLA4 typically has lower levels of B cells, or “attack” cells, and T cells – white blood cells that detect infection- that may not function properly. Bone marrow transplantation can create new B cells and T cells that work well, although it can be risky. With proper management of symptoms, people with CTLA4 deficiency are able to manage the disease and lead relatively normal lives.