Serum IL-17 and IL-23 levels and autoantigen-specific Th17 cells are elevated in patients with ANCA-associated vasculitis

• Published in: Nephrology, dialysis, transplantation Vol. 25; no. 7; pp. 2209 - 2217
• Main Authors: Nogueira, Estela, Hamour, Sally, Sawant, Devika, Henderson, Scott, Mansfield, Nicholas, Chavele, Konstantia-Maria, Pusey, Charles D., Salama, Alan D.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.2010
• Subjects: Adeno-associated virus; ANCA; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - blood; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - immunology; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - pathology; Biological and medical sciences; Case-Control Studies; cytokines; Emergency and intensive care: renal failure. Dialysis management; Female; Humans; IL-17; IL-23; Intensive care medicine; Interferon-gamma - blood; Interleukin-17 - blood; Interleukin-1beta - blood; Interleukin-23 - blood; Interleukin-6 - blood; Male; Medical sciences; Middle Aged; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Severity of Illness Index; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - pathology; Th17; vasculitis; Kidney disease; Human; Urinary system disease; Antineutrophil cytoplasmic antibody; Hemodialysis; Cytokine; Cardiovascular disease; IL-23; Vascular disease; Extrarenal dialysis; Vasculitis; ANCA; Renal failure; IL-17; cytokines; Th17
• ISSN: 0931-0509; 1460-2385; 1460-2385
• DOI: 10.1093/ndt/gfp783

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-1β, as well as the Th1 cytokine IFN-γ. ELISPOT was performed to measure autoantigen-specific recall T cell responses in convalescent patients and the frequency of IL-17- and IFN-γ-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-γ 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-γ-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.