Increased HLA-DR and CD44 antigen expression in the gut: evidence of extraarticular immunological activity in rheumatoid arthritis

To examine the gastrointestinal (GI) immune system in rheumatoid arthritis (RA) for evidence of activation.Duodenal biopsies from 25 patients with RA were obtained by endoscopy. Single cell suspensions from the epithelial layer and lamina propria were prepared. Flow cytometry was used to examine the expression of CD4, CD8, T cell receptor-gammadelta (TCR-gammadelta), TCR-alphabeta, HLA-DR, CD44, and interleukin 2 receptor on gut T lymphocytes. Fifteen disease control (DC) individuals and 6 patients with osteoarthritis (OA) taking longterm nonsteroidal antiinflammatory drug (NSAID) therapy were also investigated. Peripheral blood T lymphocytes from all individuals were examined for the expression of these surface molecules.HLA-DR expression was significantly increased on intraepithelial lymphocytes (IEL) and enterocytes from patients with RA (n = 13) compared with the 2 control groups (p0.01). Immunohistochemistry also revealed increased expression of HLA-DR on enterocytes from patients with RA. RA IEL (n = 6) expressed significantly higher levels of CD44 (p0.02). In the lamina propria, a small but significant gammadelta T lymphocyte population (mean 5.5%, range 2-12%) was detected in rheumatoid factor positive RA patients (n = 8) compared with RF negative RA patients (n = 8, mean 2%, range 0.4-6%; p0.01) and the disease control group (n = 15, mean 2%, range 0.5-5%; p0.01). None of these changes were detectable in peripheral blood lymphocytes from patients with RA.This study demonstrates evidence of activation of specific components of the GI immune system in RA. Peripheral blood T lymphocytes from patients with RA did not show increased expression of activation markers, suggesting that changes in the RA GI tract are not systemic but localized. Moreover, these changes appear to be independent of NSAID therapy.