Autoantibodies to IL-17A may be correlated with the severity of mucocutaneous candidiasis in APECED patients

Adrien Katalin Sarkadi, Szilvia Taskó, Gabriella Csorba, B. Tóth, M. Erdős, L. Máródi

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)181-193
Number of pages13
JournalJournal of Clinical Immunology
Volume34
Issue number2
DOIs
Publication statusPublished - 2014

Fingerprint

Autoimmune Polyendocrinopathies
Interleukin-17
Candidiasis
Autoantibodies
Chronic Mucocutaneous Candidiasis
Antibodies
Cytokines
Blood Cells
Candida
Type 1 Autoimmune polyendocrinopathy syndrome
Cutaneous Candidiasis
Serum
Mutation
Clinical Chemistry
Nonsense Codon
Allergy and Immunology
DNA Sequence Analysis

Keywords

  • APECED
  • chronic mucocutaneous candidiasis
  • IL-17
  • IL-22

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Autoantibodies to IL-17A may be correlated with the severity of mucocutaneous candidiasis in APECED patients. / Sarkadi, Adrien Katalin; Taskó, Szilvia; Csorba, Gabriella; Tóth, B.; Erdős, M.; Máródi, L.

In: Journal of Clinical Immunology, Vol. 34, No. 2, 2014, p. 181-193.

Research output: Contribution to journalArticle

@article{7bea8bcce44443a2aaba8cbbc7c112d2,
title = "Autoantibodies to IL-17A may be correlated with the severity of mucocutaneous candidiasis in APECED patients",
abstract = "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.",
keywords = "APECED, chronic mucocutaneous candidiasis, IL-17, IL-22",
author = "Sarkadi, {Adrien Katalin} and Szilvia Task{\'o} and Gabriella Csorba and B. T{\'o}th and M. Erdős and L. M{\'a}r{\'o}di",
year = "2014",
doi = "10.1007/s10875-014-9987-5",
language = "English",
volume = "34",
pages = "181--193",
journal = "Journal of Clinical Immunology",
issn = "0271-9142",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - Autoantibodies to IL-17A may be correlated with the severity of mucocutaneous candidiasis in APECED patients

AU - Sarkadi, Adrien Katalin

AU - Taskó, Szilvia

AU - Csorba, Gabriella

AU - Tóth, B.

AU - Erdős, M.

AU - Máródi, L.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - APECED

KW - chronic mucocutaneous candidiasis

KW - IL-17

KW - IL-22

UR - http://www.scopus.com/inward/record.url?scp=84898838687&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84898838687&partnerID=8YFLogxK

U2 - 10.1007/s10875-014-9987-5

DO - 10.1007/s10875-014-9987-5

M3 - Article

VL - 34

SP - 181

EP - 193

JO - Journal of Clinical Immunology

JF - Journal of Clinical Immunology

SN - 0271-9142

IS - 2

ER -