Patients
What is CTLA-4 deficiency?
CTLA-4 deficiency is caused by a very rare hereditary defect in one of the two copies of the CTLA4 gene. The CTLA-4 protein plays an important role in the regulation of the immune system, and a defect in the CTLA4 gene leads to a reduced production of the protein with the consequence of an immune dysregulation, which means that the immune system can no longer function sufficiently.
Which symptoms can occur in patients with CTLA-4 deficiency?
The type of symptoms and their severity can vary in individual patients. In many patients, first symptoms may include diarrhea and an increased susceptibility to respiratory tract infections such as pneumonia, bronchitis and sinusitis starting in childhood. An incidence of more than three infections per year requiring antibiotic treatment is usually considered a high susceptibility to infections in adults. In other patients first symptoms manifest in the form of autoimmune diseases, in which the body forms antibodies against itself. This can lead to a variety of conditions such as the reduction of the number of blood cells (autoimmune cytopenia) or an inflammation of the thyroid gland (autoimmune thyroiditis). Some patients may develop symptoms later in life. About two thirds of patients present with benign nodules, called granulomas, that can manifest for example in the lung. Other patients may suffer from an infiltration of immunological cells (lymphocytes) into various organs such as the intestine, kidneys, liver, brain, and bone marrow. This can lead to inflammation or a decline of organ function. In the lung often a combination of these two conditions can develop, which is called granulomatous lymphocytic intestinal lung disease (GLILD). This can lead to a structural damage in the lung tissue with symptoms like shortness of breath, chronic cough and purulent sputum.
How do I know that I have CTLA-4 deficiency?
Blood tests can determine whether there is an impairment of the immune system and whether, the antibody levels are sufficiently high to protect the body against pathogens. However, the antibody levels are only reduced in about two thirds of the patients and blood tests do not suffice to diagnose CTLA-4 deficiency. Rather a genetic test of the patients' DNA has to be performed in a specialized laboratory to determine if a defect in the CTLA4 gene can explain the clinical symptoms. Because this defect is rare, at this point we recommend testing only for patients who have already been diagnosed or suspected of having a primary immunodeficiency (PID) or an immune dysregulation syndrome. The CCI (Center for Chronic Immunodeficiency) in Freiburg is specialized for primary immunodeficiencies and is equipped to perform this genetic test.
However, mutations in CTLA4 do not always lead to clinical symptoms. Several individuals are known to carry the mutation and are clinically healthy. This phenomenon is known in medical practice and is called “reduced penetrance”. The factors that lead to this phenomenon are under investigation at the CCI.
As a mutation carrier, do I need to take any precautions?
Patients with a primary immunodeficiency are often not capable of building up an immune response against vaccinations, which means that there is no immunization protection. Normally, the body creates an immune memory so that the next time it is confronted with a pathogen it knows better how to defend itself but often this is not the case in patients with immunodeficiencies. Whether you have a higher susceptibility for infections can be checked by your general practitioner by measuring antibody titers and cellular composition of the white blood cells and lymphocytes.
Treatment options
Treatment depends on the clinical manifestations and the severity of the symptoms in each individual patient. Many patients suffer from a lack of antibodies that are essential for fighting infections and therefore have to receive intravenous or subcutaneous injections of manufactured antibodies. Because these antibodies are degraded in the body over time, patients have to be infused on a regular basis. Patients suffering from recurrent infections may need antibiotic prophylaxis.
If the clinical manifestations include autoimmune diseases or infiltration of immune cells into the organs the treatment of immunosuppressive drugs to stabilize the patient’s immune system might be necessary. In addition there is also the option to administer a drug called Abatacept, which works similar to the body’s own CTLA-4.
Can I transmit CTLA-4 deficiency to other individuals?
Clinical manifestations in CTLA-4 deficiency are caused by a hereditary defect in the genetic information that is passed down to the children with a chance of 50%. In some patients this defect can occur spontaneously without the parents passing it on. The resulting symptoms are restricted to the individual mutation carrier and cannot be transferred to other individuals.