Serum IL-17 and IL-23 levels and autoantigen-specific Th17 cells are elevated in patients with ANCA-associated vasculitis
| Autor: | Scott R. Henderson, Devika Sawant, Estela Nogueira, Nicholas Mansfield, Alan D. Salama, Sally Hamour, Charles D. Pusey, Konstantia-Maria Chavele |
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| Rok vydání: | 2010 |
| Předmět: |
Male
media_common.quotation_subject medicine.medical_treatment T cell Interleukin-1beta Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Interleukin-23 Severity of Illness Index Interferon-gamma T-Lymphocyte Subsets medicine Humans Anti-neutrophil cytoplasmic antibody media_common Transplantation Interleukin-6 business.industry Convalescence ELISPOT Interleukin-17 Middle Aged medicine.disease Cytokine medicine.anatomical_structure Nephrology Case-Control Studies Immunology Female Interleukin 17 business Vasculitis Systemic vasculitis |
| Zdroj: | Nephrology Dialysis Transplantation. 25:2209-2217 |
| ISSN: | 1460-2385 0931-0509 |
| DOI: | 10.1093/ndt/gfp783 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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