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

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.
Competing Interests: KG reports personal fees from Roche, outside the submitted work. BD reports consulting fees from Roche, Chugai, Sanofi, and sponsorship grants for international meetings and workshops with Roche, Sanofi, AbbVie and GlaxoSmithKline. EB reports personal fees from Roche, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Reitsema, Jiemy, Wekema, Boots, Heeringa, Huitema, Abdulahad, van Sleen, Sandovici, Roozendaal, Diepstra, Kwee, Dasgupta, Brouwer and van der Geest.)