Background

AUTHOR=Reitsema Rosanne D. , Jiemy William F. , Wekema Lieske , Boots Annemieke M. H. , Heeringa Peter , Huitema Minke G. , Abdulahad Wayel H. , van Sleen Yannick , Sandovici Maria , Roozendaal Caroline , Diepstra Arjan , Kwee Thomas , Dasgupta Bhaskar , Brouwer Elisabeth , van der Geest Kornelis S. M. TITLE=Contribution of pathogenic T helper 1 and 17 cells to bursitis and tenosynovitis in polymyalgia rheumatica JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.943574 DOI=10.3389/fimmu.2022.943574 ISSN=1664-3224 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.