Autoimmunity in PI causes blood disorders, GI issues, lung problems

While recurrent infections are a hallmark of primary immunodeficiency (PI), some individuals with PI also cope with autoimmunity, a condition where the immune system mistakenly attacks different organ systems in the body.

“The reason why these immune deficiencies (can lead to) autoimmunity is oftentimes the genetic change that is responsible for causing these (conditions) is important in the process that regulates the immune response. When the regulation is off, the immune system gets confused and starts attacking different parts of the body. It doesn't know that it's not supposed to do that, and that's why autoimmunity can develop,” explained Dr. Alice Chan, a pediatric immunologist, rheumatologist, and allergist at the University of California San Francisco Benioff Children’s Hospital in an Immune Deficiency Foundation presentation on autoimmune issues and PI.

Autoimmune issues occur in both adults and children and most commonly in conjunction with the following PIs:

• Common variable immune deficiency (CVID).
• Chronic granulomatous disease (CGD).
• Wiskott-Aldrich syndrome (WAS).
• Primary immune regulatory disorders (PIRD).

A study of over 2,000 patients with CVID in the French National Primary Immunodeficiency Registry found that 26% had at least one autoimmune condition and that some people developed several autoimmune problems.

“This makes sense in the context that we know that a lot of these patients have genetic problems where the immune system is not being regulated correctly, so we would expect that there's potential for them to have multiple immune system issues going on,” said Chan.

The most common autoimmune issue associated with PI is autoimmune cytopenia, a condition in which immune cells attack the red blood cells, platelets, or neutrophils. The different types of autoimmune cytopenia include:

• Immune thrombocytopenia purpura (ITP), where the immune system attacks platelets, resulting in low platelet counts that cause easy bruising, spontaneous bloody noses, or prolonged bleeding.
• Autoimmune hemolytic anemia (AIHA), where the immune system attacks red blood cells, causing anemia and sometimes requiring blood transfusions.
• Evans syndrome, which is characterized by two or more cytopenias.

Doctors treat autoimmune cytopenia with steroids but also use medicine to dampen the immune system, such as high doses of immunoglobulin (Ig) treatment therapy, a drug called rituximab, which removes B cells (if they are doing the attacking), or sirolimus, an immune suppressant that prevents T cells from attacking the blood.

Gastrointestinal autoimmune issues are also common with PI and include:

• Celiac disease, in which the immune system makes an antibody that attacks gluten but also the gut.
• Inflammatory bowel diseases (IBD), like Crohn’s disease and ulcerative colitis, which affect the colon.
• Autoimmune enteropathy, where the immune system attacks the lining of the intestines.
• Autoimmune hepatitis, where the immune system attacks the liver.

Avoiding gluten, taking steroids, or using targeted monoclonal antibodies assist in controlling gastrointestinal autoimmune issues.

The immune system can also attack endocrine organs such as the thyroid, causing Hashimoto’s disease, or the pancreas, leading to type 1 diabetes. Doctors can treat endocrine problems by replacing missing hormones.

Autoimmunity in the lungs can lead to granulomatosis and lymphocytic interstitial lung disease (GLILD), which develops in 25% of patients with CVID, or interstitial lung disease (ILD), both of which cause severe breathing problems. Doctors use a host of drugs to treat these conditions, including steroids, rituximab to reduce B cells, and abatacept to control T cells. Other immunosuppressants such as azathioprine, mycophenolate, and mofetil may also be used to treat lung problems.

Other autoimmunities experienced by PI patients include rheumatological issues like arthritis and lupus, treated with steroids, monoclonal antibodies, and other immunosuppressants, and skin conditions for which doctors may prescribe ointments and immunosuppressants.

Chan said the more details providers can determine about the PI or the autoimmune issue through diagnostic testing, the more successful they will be in improving the health of patients.

“Treatment is targeted to the specific immune (variant). If we can identify the specific genetic cause or determine the type of disease that's involved, whether it be, for example, autoimmune cytopenias or arthritis, this can really help us pin down which therapy would be best to treat that disease or organ manifestation,” said Chan.