title: 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.
authors: Department of Immunology, Haartman Institute, and Research Programs Unit, Immunobiology, University of Helsinki , Helsinki , Finland .
authors: Sini M
authors: SM
authors: Laakso
authors: Eliisa
authors: E
authors: Kekäläinen
authors: Nelli
authors: N
authors: Heikkilä
authors: Helga
authors: H
authors: Mannerström
authors: Kai
authors: K
authors: Kisand
authors: Pärt
authors: P
authors: Peterson
authors: Annamari
authors: A
authors: Ranki
authors: T Petteri
authors: TP
authors: Arstila
mesh_terms: D000328:Adult; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007378:Interleukins / Q000097:blood / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000097:blood / Q000235:genetics / Q000276:immunology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014373:Tuberculin / Q000494:pharmacology*; D000097043:Interleukin-22
chemical_list: D001500:BCG Vaccine; D007378:Interleukins; D012313:RNA; D014373:Tuberculin; D000097043:Interleukin-22
keywords: APECED; APS-1; Human; autoimmunity; cytokines