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.