An infant boy has recurrent staphylococcal cold abscesses of the scalp and neck, severe eczema, coarse facies, retention of primary teeth, and recurrent sinopulmonary infections with pneumatocele formation. Serum IgE is markedly elevated at 12,000 IU/mL. Flow cytometry shows reduced Th17 cells. The mutated gene encodes:

• A STAT3, impairing IL-6 and IL-23 signaling needed for Th17 differentiation ✓
• B DOCK8, disrupting actin cytoskeletal remodeling in lymphocytes
• C WASP, impairing actin polymerization in hematopoietic cells
• D IL12RB1, blocking IL-12 responsiveness of NK and T cells

Explanation

Autosomal dominant hyper-IgE (Job) syndrome results from dominant-negative STAT3 mutations. Defective STAT3 signaling downstream of IL-6 and IL-23 impairs Th17 generation, explaining susceptibility to extracellular bacteria and Candida, while elevated IgE, cold abscesses, eczema, retained teeth, and pneumatoceles complete the picture. DOCK8 deficiency causes a recessive combined immunodeficiency with viral susceptibility and no skeletal or dental findings, and WAS features thrombocytopenia with small platelets rather than cold abscesses.

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.