Serum IL-17 and IL-23 levels and autoantigen-specific Th17 cells are elevated in patients with ANCA-associated vasculitis.
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.
Nogueira
Estela
E
Imperial College Kidney and Transplant Institute, Division of Medicine, Imperial College London, Hammersmith Hospital, London, UK.
Hamour
Sally
S
Sawant
Devika
D
Henderson
Scott
S
Mansfield
Nicholas
N
Chavele
Konstantia-Maria
KM
Pusey
Charles D
CD
Salama
Alan D
AD
D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood* / Q000276:immunology / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000097:blood*; D053583:Interleukin-1beta / Q000097:blood; D053759:Interleukin-23 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology*
D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D015850:Interleukin-6; D007371:Interferon-gamma