Contribution of pathogenic T helper 1 and 17 cells to bursitis and tenosynovitis in polymyalgia rheumatica

Abstract

Background: Although polymyalgia rheumatica (PMR) is a very common rheumatic inflammatory disease, current insight into the pathobiology of PMR is limited and largely based on studies in blood. We investigated T helper 1 (T_H1) and T helper 17 (T_H17) cell responses in blood, synovial fluid and bursa tissue of patients with PMR.

Materials and methods: Blood samples were collected from 18 patients with new-onset PMR and 32 healthy controls. Synovial fluid was aspirated from the inflamed shoulder bursae or biceps tendon sheath of 13 patients. Ultrasound-guided biopsies of the subacromial-subdeltoid (SASD) bursa were obtained from 11 patients. T cells were examined by flow cytometry, immunohistochemistry and immunofluorescence staining.

Results: Besides an increase of T_H17 (CD4⁺IL-17⁺IFN-γ^-) cells and T cytotoxic 17 (T_C17; CD8⁺IL-17⁺IFN-γ^-) cells, no other major changes were noted in the circulating T cell compartment of patients with PMR. Absolute numbers of CD4⁺ and CD8⁺ T cells were similar in blood and synovial fluid of patients with PMR. Synovial fluid T cells showed an effector-memory (CD45RO⁺CCR7^-) phenotype. Percentages of T_H1 (CD4⁺IFN-γ⁺IL-17^-) cells and T_H1/T_H17 (CD4⁺IFN-γ⁺IL-17⁺) cells, but not T_H17 or T_C17 cells, were increased in the synovial fluid. Bursa tissue biopsies contained a small number of T cells, which were mostly CD8 negative. The majority of bursa tissue T cells produced IFN-γ but not IL-17. For comparison, B cells were scarcely detected in the bursa tissue.

Conclusion: Although the circulating T_H17 cell pool is expanded in patients with PMR, our findings indicate that T_H1 cells are involved in the inflammation of bursae and tendon sheaths in this condition. Our study points towards the T_H1 cell pathway as a potential target for therapy in PMR.

Keywords: T cells; T helper 1; T helper 17; polymyalgia rheumatica; ultrasound guided biopsy.