Question 1 · Hard
A 9-year-old girl has had repeated Staphylococcus aureus skin abscesses that are swollen but barely warm or red, two pneumonias that left air-filled lung cysts (pneumatoceles), recurrent oral and nail candidiasis, and eczema since infancy. Two primary teeth have not fallen out. Results: WBC 9.8 x 10^3/µL [9.8 x 10^9/L]; neutrophils 6.0 x 10^3/µL; eosinophils 1.1 x 10^3/µL; dihydrorhodamine (DHR) oxidative burst normal; IgG, IgA and IgM within age ranges; IgE 4,600 IU/mL (reference < 200); CD4 and CD8 T-cell counts normal. Poor development of which CD4 T-cell subset best explains her infections?
- ATh17 cells
- BTh2 cells
- CTh1 cells
- DRegulatory T cells
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Answer: A · Th17 cells
Cold staphylococcal abscesses, pneumatoceles, mucocutaneous candidiasis, eczema, retained primary teeth and an IgE above 2,000 IU/mL are the picture of autosomal dominant hyper-IgE (Job) syndrome, usually caused by dominant-negative STAT3 variants. STAT3 signaling is needed for naive CD4 T cells to become Th17 cells, which make IL-17 and IL-22. These cytokines make skin and airway epithelium release neutrophil-attracting chemokines and antimicrobial peptides, so neutrophils that are normal in number and oxidative burst are not called into the tissue, and Candida is not controlled. The very high IgE and eosinophils are features of the syndrome, not signs of missing Th2 cells. The normal DHR test separates this from chronic granulomatous disease, which also causes staphylococcal abscesses.
- B: Th2 activity is not lacking here; IgE and eosinophils are raised.
- C: Th1 cells and IFN-gamma mainly defend against mycobacteria and Salmonella, not staphylococci and Candida.
- D: Failure of regulatory T cells (IPEX) causes autoimmunity and enteropathy, not cold abscesses.