In vivo analysis of helper T cell responses in patients with autoimmune polyendocrinopathy – candidiasis – ectodermal dystrophy provides evidence in support of an IL-22 defect

Abstract

Autoimmune polyendocrinopathy – candidiasis – ectodermal dystrophy (APECED) is caused by mutations in the Autoimmune regulator (AIRE) gene and is associated with neutralizing anti-cytokine autoantibodies. We have used an in vivo challenge model to analyze antigen-specific CD4⁺ T cell responses. Bacille Calmette–Guérin (BCG)-vaccinated patients and controls were injected tuberculin intradermally, skin blisters were induced by suction on the indurations and on unexposed skin, and the infiltrating cells harvested. The patients had a quantitatively normal CD4⁺ T cell response and no significant abnormalities in the expression of T helper type (Th) 1- or Th2-related genes. The expression of interleukin (IL)-22, in contrast, was lower in the patients. Two patients, both with a pre-existing ocular keratopathy, experienced a relapse of keratoconjunctivitis, suggesting a possible immunological basis for this APECED component. Our in vivo data are compatible with a selective IL-22 defect in the activated CD4⁺ T cells of APECED patients, affecting also unexposed skin in steady-state conditions.

• APECED
• APS-1
• autoimmunity
• cytokines
• Human

Acknowledgements

We thank Leena Petman of Skin and allergy Hospital and Tamás Bazsinka of Haartman Institute for expert technical help.