Immunodeficiency by defective expression of MHC class II

Immunodeficiency by defective expression of MHC class II, also known as MHC class II deficiency or Bare Lymphocyte Syndrome type II (BLS type II), is a rare and severe combined immunodeficiency disorder in which the molecules of the major histocompatibility complex class II (MHC II) are not properly expressed on the surface of immune cells. MHC class II molecules are essential for presenting antigens to CD4+ T-helper lymphocytes, and their absence leads to a profound defect in cellular and humoral immunity. The disease is caused by mutations in genes encoding transcription factors that regulate MHC II expression, including CIITA (MHC2TA), RFXANK, RFX5, and RFXAP. These mutations impair the ability of antigen-presenting cells such as B lymphocytes, macrophages, and dendritic cells to activate CD4+ T cells. Affected infants typically present in the first year of life with severe, recurrent, and often life-threatening infections, particularly of the respiratory and gastrointestinal tracts. Common clinical features include chronic diarrhea, failure to thrive, pneumonia, bronchiectasis, and susceptibility to opportunistic infections caused by bacteria, viruses, fungi, and protozoa such as Cryptosporidium. Patients characteristically have a marked reduction in CD4+ T lymphocytes, hypogammaglobulinemia, and an inability to mount antigen-specific immune responses. Autoimmune cytopenias and liver disease (particularly sclerosing cholangitis associated with Cryptosporidium infection) may also occur. Without treatment, the prognosis is poor, with most patients succumbing to infections in early childhood. The only curative treatment currently available is hematopoietic stem cell transplantation (HSCT), ideally performed early in life before the development of organ damage. Supportive care includes prophylactic antibiotics, antifungal agents, immunoglobulin replacement therapy, and aggressive treatment of infections. The condition is more prevalent in populations with higher rates of consanguinity, particularly in North Africa and the Middle East.

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