IL-6-specific autoantibodies among APECED and thymoma patients.
Immun Inflamm Dis
; 4(2): 235-243, 2016 06.
Article
em En
| MEDLINE
| ID: mdl-27957331
ABSTRACT
INTRODUCTION:
Both autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and the rare thymoma patients with chronic mucocutaneous candidiasis (CMC) have neutralizing autoantibodies to Th17 cytokines and significant defects in production of IL-22 and IL-17F by their T cells. The cause of these defects is unknown. We hypothesized that they might result from autoimmunity against upstream cytokines normally responsible for generating and maintaining Th17 cells.METHODS:
Luciferase immunoprecipitation (LIPS) was used to screen for autoantibodies to IL-6, IL-1ß, TGF-ß3, IL-21, and IL-23 in patients with APECED or thymoma. We used Western blotting to assess the conformation-dependence of the IL-6 autoantibodies and flow cytometric analysis of intracellular phospho-STAT3 induction to assess IL-6-neutralizing capacity in IgGs isolated from patient and control sera. We also used Luminex xMAP to measure serum cytokine levels.RESULTS:
We found autoantibodies binding to conformational epitopes of IL-6 in 19.5% of 41 patients with APECED and 12.5% of 104 with thymoma-especially in those with long disease durations. The autoantibodies were predominantly of IgG1 subclass and failed to neutralize IL-6 activity. Notably, serum levels of the IL-6 and IL-17A cytokines were higher in anti-IL-6 seropositive than-negative APECED patients or healthy controls. We also detected autoantibody binding to IL-23 in 27.9% of thymoma patients, resulting from cross-recognition through the p40 subunit it shares with IL-12.CONCLUSIONS:
IL-6 and IL-17A elevation in these seropositive patients suggests that antibody-binding may protect IL-6 from degradation and prolong its half-life in vivo.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
/
Neoplasias do Timo
/
Interleucina-6
/
Poliendocrinopatias Autoimunes
Limite:
Humans
Idioma:
En
Revista:
Immun Inflamm Dis
Ano de publicação:
2016
Tipo de documento:
Article