Immunodeficiency syndrome with autoimmunity

Immunodeficiency syndrome with autoimmunity (Orphanet code 169355) is a broad clinical category encompassing a group of rare genetic disorders in which the immune system is both deficient in its ability to fight infections and dysregulated in a way that leads it to attack the body's own tissues. These conditions arise from mutations in genes critical to immune cell development, regulation, or signaling, resulting in a paradoxical combination of immunodeficiency (increased susceptibility to infections) and autoimmunity (immune-mediated damage to healthy organs). Body systems commonly affected include the hematologic system (autoimmune cytopenias such as hemolytic anemia, thrombocytopenia, and neutropenia), the gastrointestinal tract (autoimmune enteropathy), the endocrine system (autoimmune thyroiditis, type 1 diabetes), and the skin. Patients typically present in infancy or childhood with recurrent or severe infections alongside one or more autoimmune manifestations. Lymphoproliferation, including lymphadenopathy and splenomegaly, may also be observed. Specific genetic subtypes within this category include defects in genes such as CTLA4, LRBA, STAT3 gain-of-function, PIK3CD, AIRE, FOXP3 (causing IPEX syndrome), and others that regulate immune tolerance and T-regulatory cell function. The clinical severity and spectrum of autoimmune features vary widely depending on the underlying genetic defect. Management is multidisciplinary and depends on the specific diagnosis. Treatment strategies include immunoglobulin replacement therapy for antibody deficiency, immunosuppressive agents (such as sirolimus, mycophenolate mofetil, or targeted biologics like abatacept) to control autoimmunity, and in severe cases, hematopoietic stem cell transplantation (HSCT), which can be curative for certain subtypes. Early genetic diagnosis through next-generation sequencing panels is increasingly important for guiding targeted therapy and improving outcomes.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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