A 7-year-old girl has recurrent severe mucocutaneous Candida albicans infections, hypoparathyroidism, and adrenal insufficiency. She also has nail dystrophy and dental enamel hypoplasia. Genetic analysis reveals loss-of-function mutation of a transcription factor expressed in thymic medullary epithelial cells. The normal function of this gene product is:

• A Mediating Fas-induced apoptosis of autoreactive peripheral lymphocytes
• B Rearranging TCR beta chains during thymocyte development
• C Promoting expression of tissue-specific self-antigens in the thymus for negative selection of autoreactive T cells ✓
• D Transporting peptides into the endoplasmic reticulum via TAP

Explanation

This is autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APS-1/APECED) caused by mutation of AIRE. AIRE drives promiscuous ectopic expression of tissue-restricted self-antigens such as insulin and parathyroid hormone by medullary thymic epithelial cells, allowing deletion of developing autoreactive T cells during central tolerance. Its loss permits multiorgan autoimmunity plus chronic candidiasis. Fas defects (option A) cause ALPS with lymphadenopathy and autoimmune cytopenias, and TAP deficiency (option D) causes bare lymphocyte syndrome type 1.

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.