The Immune Response to Autologous Bacteroides in Ankylosing Spondylitis Is Characterized by Reduced Interleukin 10 Production

Abstract

Ileocolitis is a recognized feature of ankylosing spondylitis (AS) and is likely to play a role in the pathogenesis of AS, in conjunction with the normal intestinal microbiota. In order to investigate the host immune response in AS, we measured cytokines in tissue culture following exposure of peripheral blood mononuclear cells (PBMC) to autologous colonic bacteria. Twenty-one patients with AS and 21 matched controls were recruited. Subjects in the AS group were assessed clinically. Bacteroides species belonging to the B. fragilis group were selectively cultured from stool samples and paired with blood samples from each participant. Ten cultures of autologous Bacteroides were randomly selected from cultures grown from the fecal specimens of each of the 21 patients with AS and 21 controls. These were then tested for reactivity with PBMC and the cytokines produced by proliferating lymphocytes [interleukin 10 (IL-10), IL-17, interferon-gamma, tumor necrosis factor-alpha] were measured in cell culture supernatants. Differences between groups were analyzed using censored normal regression analysis. The patients with AS had severe active AS with Bath AS Disease Activity Index 5.5 (+/-1.6) and C-reactive protein (mg/l) 13.8 (+/-12.2) (mean+/-standard deviation). IL-10 concentrations in ex vivo assay supernatants were lower in the AS group compared with controls (p=0.047). There were no statistically significant differences between the groups for other cytokines. In AS, reduced IL-10 production in response to stimulation with autologous Bacteroides cultures may represent a mechanism by which intestinal inflammation develops and persists, a situation analogous to inflammatory bowel disease.