Any common variable immunodeficiency in which the cause of the disease is a mutation in the CD81 gene.

Activated PI3K-delta syndrome (also known as APDS) is a disorder that impairs the immune system. Individuals with this condition often have low numbers of white blood cells (lymphopenia), particularly B cells and T cells. Normally, these cells recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection. The severity of activated PI3K-delta syndrome varies widely. Some people may have multiple, severe infections while others show mild symptoms to none at all.\n\nMost commonly, people with activated PI3K-delta syndrome develop recurrent infections that begin in childhood, particularly in the lungs, sinuses, and ears. Over time, recurrent respiratory tract infections can lead to a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems. People with activated PI3K-delta syndrome may also have chronic active viral infections, such as Epstein-Barr virus, herpes simplex virus, or cytomegalovirus infections.\n\nAnother possible feature of activated PI3K-delta syndrome is abnormal clumping of white blood cells. These clumps can lead to enlarged lymph nodes (lymphadenopathy) or an enlarged spleen (splenomegaly). The white blood cells can also build up to form solid masses (nodular lymphoid hyperplasia), usually in the moist lining of the airways or intestines. While nodular lymphoid hyperplasia is not cancerous (benign), activated PI3K-delta syndrome increases the risk of developing forms of blood cancer called Hodgkin lymphoma and non-Hodgkin lymphoma.\n\nThere are two types of activated PI3K-delta syndrome, each with different genetic causes.\n\nSome people with activated PI3K-delta syndrome develop autoimmunity, which occurs when the body attacks its own tissues and organs by mistake.

IMD24 is an autosomal recessive immunodeficiency characterized by the impaired capacity of activated T and B cells to proliferate in response to antigen receptor-mediated activation. Patients have early onset of severe chronic viral infections, mostly caused by herpesviruses, including Epstein-Barr virus (EBV) and varicella zoster virus (VZV); they also suffer from recurrent encapsulated bacterial infections, a spectrum typical of a combined deficiency of adaptive immunity (CID) (summary by Martin et al., 2014).

Any autoimmune disease, multisystem, infantile-onset in which the cause of the disease is a mutation in the ZAP70 gene.

Immunodeficiency-109 with EBV-induced lymphoproliferation (IMD109) is an autosomal recessive primary immune disorder characterized by onset of recurrent sinopulmonary infections in childhood. Affected individuals are susceptible to infection with EBV and develop EBV viremia and EBV-associated lymphoproliferative disease or B-cell lymphoma. Immunologic work-up shows normal levels of T, B, and NK cells, with defective CD8+ T cell function after stimulation. Some patients may have hypogammaglobulinemia and poor antibody response to stimulation (Alosaimi et al., 2019).

Infantile-onset multisystem autoimmune disease-3 (ADMIO3) is an autosomal recessive disorder of immune dysregulation characterized by the onset of various systemic autoimmune manifestations in the first months or years of life. Features may include hypothyroidism, type 1 diabetes mellitus, systemic inflammatory manifestations (fever, hepatomegaly), and autoimmune cytopenias. Laboratory studies show normal levels of T, B, and NK cells, but CD4+ (see 186940) T cells demonstrate hyperproliferation when stimulated in vitro (Janssen et al., 2022). For a discussion of genetic heterogeneity of ADMIO, see ADMIO1 (615952).