Is the enthesitis-related arthritis subtype of juvenile idiopathic arthritis a form of chronic reactive arthritis?

Abstract

Enteric organisms are known to trigger reactive arthritis. The enthesitis-related arthritis (ERA) form of juvenile idiopathic arthritis (JIA) clinically resembles reactive arthritis. Therefore, we looked for a role of enteric bacteria in ERA. Synovial fluid (SF) was obtained from 26 patients with ERA and 10 patients with rheumatoid arthritis (RA). Blood specimens were also obtained from patients with ERA and from 10 normal individuals. Lymphocyte proliferation assays were done on whole blood and SF mononuclear cells using as antigens crude lysates of the enteric bacteria Salmonella typhimurium, Yersinia enterocolitica, Shigella flexneri and Campylobacter jejuni. Crude lysate of Escherichia coli was used as a control antigen. HLA-B27 typing was done using the polymerase chain reaction. Homing of gut-specific T cells (CD103+) to the synovial compartment was studied using tri-colour flow cytometry. The antigen-specific cytokine profile was determined by flow cytometry. Antigen-specific lymphoproliferative responses were observed in 14 of 26 patients. Among these patients, 12 showed a response in SF (four each to S. typhimurium and C. jejuni, and in two each to S. flexneri and Y. enterocolitica), and two patients in blood (S. typhimurium in both). None of the healthy controls showed a response in the blood. Lymphoproliferative responses in SF were more frequent in patients with JIA (12/26) than in controls with RA (1/10, P < 0.05). Patients with an antigen-specific response had a higher ratio of SF/blood CD103+ T cells compared with those with no antigen-specific response (P < 0.01). Antigen-specific as well as mitogen-stimulated cytokine production showed a Th1 bias. Enteric bacteria may have a role in exacerbation of disease in patients with ERA. The immune response in patients with ERA is Th1-dominant.