Sporadic enteric reactive arthritis and undifferentiated spondyloarthropathy: evidence for involvement of Salmonella typhimurium

Abstract

OBJECTIVE: To define the candidate bacterial trigger and cytokine profile of synovial fluid mononuclear cells (SFMC) in patients with sporadic enteric reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA). METHODS: The study group comprised 10 patients with ReA and 23 with uSpA who fulfilled European Spondylarthropathy Study Group criteria. Ten patients with rheumatoid arthritis (RA) served as disease controls. IgG, IgA, and IgM antibodies to Shigella flexneri, Salmonella typhimurium, and Yersinia enterocolitica were measured in sera and SF by ELISA. Peripheral blood mononuclear cell (PBMC) and SFMC proliferation assays were done in the presence or absence of crude bacterial lysates. Bacterial antigens and DNA in synovial cells were detected by indirect immunofluorescence and polymerase chain reaction, respectively. Interferon-g (IFN-g), interleukin 10 (IL-10), and IL-4 were measured in 18 h SFMC culture supernatants in presence of bacterial lysate. RESULTS: Antibodies to S. typhimurium were significantly elevated in the sera of 8 of 25 patients compared to controls (0/22; p < 0.05). The ratio of SF:serum anti-salmonella IgA was significantly higher in patients compared to controls (p < 0.0002). The ratio of SF:serum IgA antibodies to S. typhimurium was higher than that for S. flexneri (p < 0.007) and Y. enterocolitica (p < 0.05). Out of 25 patients, 8, 2, and none had elevated antigen-specific SFMC proliferation response to S. typhimurium, S. flexneri, and Y. enterocolitica, respectively, whereas no control had elevated response. Salmonella antigens were detected in the synovial cells of 4 out of 14 patients. There was significantly higher IFN-g production from SFMC of patients who had increased proliferative response to Salmonella (LTT+) in the presence of Salmonella antigens compared to antigen control. The mean +/- SD of the ratio of IFN-g:IL-10 in the LTT+ patients was significantly lower compared to controls. Conclusion. S. typhimurium is probably one of the triggers for enteric ReA and uSpA in our cohort of patients, and the immune response is characterized by increased production of both IL-10 and IFN-g.