Document Detail

Serum IL-17 and IL-23 levels and autoantigen-specific Th17 cells are elevated in patients with ANCA-associated vasculitis.
MedLine Citation:
PMID:  20100727     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The Th17 subset has been implicated in the pathogenesis of a number of autoimmune diseases. However, little is known about its role in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). We measured serum levels of IL-17A and associated upstream cytokines and the frequency of IL-17-producing autoantigen-specific T cells in patients with AAV. METHODS: ELISA on sera from acute (n = 28) and convalescent (n = 65) patients with AAV from Hammersmith Hospital was performed for IL-17A and the associated upstream cytokines IL-23, IL-6 and IL-1beta, as well as the Th1 cytokine IFN-gamma. ELISPOT was performed to measure autoantigen-specific recall T cell responses in convalescent patients and the frequency of IL-17- and IFN-gamma-producing cells. RESULTS: Serum IL-17A and IL-23 levels were significantly elevated in acute AAV patients compared to healthy controls (P < 0.01 and P < 0.001, respectively), but importantly, remained elevated in a proportion of convalescent patients. By contrast, no significant differences in IFN-gamma levels were detected between patient groups and controls. Patients with elevated levels of IL-23 compared to those with low IL-23 had more active disease as measured by Birmingham Vasculitis Activity Score (P < 0.05) and had higher ANCA titres (P < 0.05). Critically, immunosuppressive therapy did not always effectively suppress IL-23 or IL-17 production. Additionally, autoantigen-specific IL-17-producing, but not IFN-gamma-producing, cells were significantly elevated in patients during disease convalescence compared to healthy controls. CONCLUSIONS: These data implicate the Th17 axis and specifically IL-23 as mediators of more severe disease in AAV. Their persistence despite conventional treatment may contribute to high relapse rates.
Estela Nogueira; Sally Hamour; Devika Sawant; Scott Henderson; Nicholas Mansfield; Konstantia-Maria Chavele; Charles D Pusey; Alan D Salama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-25
Journal Detail:
Title:  Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association     Volume:  25     ISSN:  1460-2385     ISO Abbreviation:  Nephrol. Dial. Transplant.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-25     Completed Date:  2010-11-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8706402     Medline TA:  Nephrol Dial Transplant     Country:  England    
Other Details:
Languages:  eng     Pagination:  2209-17     Citation Subset:  IM    
Imperial College Kidney and Transplant Institute, Division of Medicine, Imperial College London, Hammersmith Hospital, London, UK.
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MeSH Terms
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / blood*,  immunology,  pathology*
Case-Control Studies
Interferon-gamma / blood
Interleukin-17 / blood*
Interleukin-1beta / blood
Interleukin-23 / blood*
Interleukin-6 / blood
Middle Aged
Severity of Illness Index
T-Lymphocyte Subsets / immunology,  pathology*
Reg. No./Substance:
0/Interleukin-17; 0/Interleukin-1beta; 0/Interleukin-23; 0/Interleukin-6; 82115-62-6/Interferon-gamma

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