A 9-year-old girl has massive cervical and axillary lymphadenopathy, splenomegaly, and repeated oral candidiasis. Biopsy shows paracortical expansion with doubling of germinal centers containing numerous apoptotic bodies. Laboratory studies reveal lymphocytosis with expanded double-negative T cells (CD3+, CD4-, CD8-) and hypergammaglobulinemia. The defective process is:

• A V(D)J recombination mediated by RAG enzymes
• B TAP-dependent peptide loading onto MHC class I molecules
• C Thymic negative selection driven by AIRE expression
• D Fas-mediated apoptosis of activated lymphocytes ✓

Explanation

Autoimmune lymphoproliferative syndrome (ALPS) results from germline mutations affecting the death receptor Fas (or its signaling). Activated lymphocytes escape apoptosis, accumulating as chronically stimulated double-negative T cells and producing lymphadenopathy, splenomegaly, hypergammaglobulinemia, and autoimmunity such as hemolytic anemia. RAG defects cause SCID with absent lymphocytes, and AIRE defects define APS-1 with mucocutaneous candidiasis plus hypoparathyroidism and adrenal insufficiency.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.