Autoantibodies to IL-17A may be Correlated with the Severity of Mucocutaneous Candidiasis in APECED Patients
- First Online:
The relative roles of various autoantibodies against IL-17-type cytokines in susceptibility to chronic mucocutaneous candidiasis (CMC) in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) remain poorly defined. The purpose of this longitudinal study was to analyze the relationship between the occurrence of mucocutaneous candidiasis and levels of anti-IL-17A, anti-IL-17F and anti-IL-22 autoantibodies. We studied six APECED patients from four families with various disease manifestations. Clinical data were collected during regular follow-up. Anti-endocrine organ antibody levels and clinical chemistry and immunology parameters were determined in routine laboratory assays on freshly isolated serum. Levels of autoantibodies against IL-17A, IL-17F, IL-22, IFN-α, IFN-ω and TNF-α, and cytokine release by Candida-exposed blood cells were determined by ELISA. Mutations were analyzed by sequencing genomic DNA. Four patients carried the germline c.769C > T homozygous nonsense mutation, which results in R257X truncation of the AIRE protein, and two patients from the same family were compound heterozygous for the c.769C > T/c.1344delC mutation. We found persistently high levels of antibodies against IL-17A in the serum samples of one patient presenting CMC since infancy and low or undetectable anti-IL-17A antibody levels in the sera of five patients with no candidiasis or without severe candidiasis. By contrast, levels of autoantibodies against IL-17F and IL-22 were higher in all patients than in healthy controls. Release of IL-17-type cytokines by Candida-exposed blood mononuclear cells was low or negligible in all patients tested. We suggest that anti-IL-17A antibodies may play an important role in the predisposition to candidiasis of APECED patients. However, the lack of severe CMC in APECED patients with high levels of IL-17F and anti-IL-22 autoantibodies clearly calls into question the role of these antibodies as the principal cause of cutaneous and mucosal candidiasis in at least some APECED patients. These data also suggest that the impaired release of IL-17-type cytokines by blood cells may be an element of the immunopathology of CMC in APECED patients.
KeywordsAPECED IL-17 IL-22 chronic mucocutaneous candidiasis
- 16.McManus BA, McGovern E, Moran GP, Healy CM, Nunn J, Fleming P, et al. Microbiological screening of Irish patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy reveals persistence of Candida albicans strains, gradual reduction in susceptibility to azoles, and incidences of clinical signs of oral candidiasis without culture evidence. J Clin Microbiol. 2011;49(5):1879–89.PubMedCentralPubMedCrossRefGoogle Scholar
- 23.Ng WF, von Delwig A, Carmicheal AJ, Arkwright PD, Abinun M, Cant AJ, et al. Impaired TH 17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Allergy Clin Immunol. 2010;126(5):1006–15.PubMedCrossRefGoogle Scholar
- 24.Orange JS, Hossny EM, Weiler CR, Ballow M, Berger M, Bonilla FA, et al. Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol. 2006;117(4 Suppl):S525–53.PubMedCrossRefGoogle Scholar
- 38.Weiler FG, Dias-da-Silva MR, Lazaretti-Castro M. Autoimmune polyendocrine syndrome type 1: case report and review of literature. Arg Bras Endocrinol Metabol. 2012;56(1):54–66.Google Scholar