The pathophysiology of polymyalgia rheumatica, small pieces of a big puzzle

Alegria, Guillermo Carvajal; Boukhlal, Sara; Cornec, Divi; Devauchelle‐Pensec, Valérie

doi:10.1016/j.autrev.2020.102670

Cited by 36 publications

(27 citation statements)

References 96 publications

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“…30 IL-6 is a multi-effect protein secreted by various normal cells and transformed lymphoid and nonlymphocytes, which is involved in various pathological processes in vivo, for instance, autoimmune disorder, inflammation, tumor cell proliferation, etc. 31 Long-term high glucose state accelerates insulin resistance in cardiomyocytes, and insulin signal transduction is inhibited. Insulin resistance is a low level of proinflammatory state, and the increased fat ratio promotes the release of inflammatory cytokines, such as TNF-α and IL-6.…”

Section: Discussionmentioning

confidence: 99%

Changes of Necroptosis in Irbesartan Medicated Cardioprotection in Diabetic Rats

Xu¹,

Tan²,

Wei³

et al. 2021

DMSO

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Background: Diabetic cardiomyopathy (DCM) is strongly linked to microvascular disease, renin-angiotensin system (RAS) activation, cardiac inflammation and cell apoptosis. Irbesartan is an angiotensin II (Ang II) receptor antagonist in RAS system, which inhibited the conversion of Ang I into Ang II, while the specific mechanism is still obscure. Objective: This study aims to investigate the expressions necroptosis RIP1-RIP3-MLKL pathway in myocardium of diabetic rats, and the protective action of irbesartan on myocardial damage. Materials and Methods: In our study, 30 Sprague-Dawley rats were divided into 5 groups: CON4W, high glucose and high caloric (HC4W), diabetes mellitus 4 weeks (DM4W group), diabetes mellitus 8 weeks (DM8W group), and irbesartan diabetes 8 weeks (Ir DM8W group). Results: We discovered that as diabetes progresses, the rats gradually lost weight, the HW/ BW ratio were increased gradually, and the cardiac function became worse accompanied with the aggravation of inflammatory injury. Meanwhile, the myocardial fibers and cells were disordered, and the expression of positive substances, RIP1 and RIP3 increased significantly. The mRNA and protein levels of myocardial RIP1, RIP3 and MLKL were all increased with the progression of DM. After the intervention of irbesartan in diabetic rats, the cardiac function was improved, whereas inflammatory injury and HW/BW ratio were decreased. Also, the myocardial fibrosis injury was attenuated, and the PAS positive substances, RIP1 and RIP3 were significantly decreased. The curative effect of irbesartan was related to decreased myocardial RIP1, RIP3 and MLKL mRNA and protein levels. Conclusion:In conclusion, irbesartan has a cardioprotective effect on the diabetic rats, and its mechanism may be connected with inhibition of RIP1-RIP3-MLKL pathway.

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Section: Discussionmentioning

confidence: 99%

Changes of Necroptosis in Irbesartan Medicated Cardioprotection in Diabetic Rats

Xu¹,

Tan²,

Wei³

et al. 2021

DMSO

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“…Current insight into the pathobiology of PMR is mostly based on studies in blood ( 11 , 12 ). An expansion of myeloid cells has been observed in the circulation of patients with PMR ( 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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BackgroundAlthough 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 (TH1) and T helper 17 (TH17) cell responses in blood, synovial fluid and bursa tissue of patients with PMR.Materials and methodsBlood 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.ResultsBesides an increase of TH17 (CD4+IL-17+IFN-γ-) cells and T cytotoxic 17 (TC17; 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 TH1 (CD4+IFN-γ+IL-17-) cells and TH1/TH17 (CD4+IFN-γ+IL-17+) cells, but not TH17 or TC17 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.ConclusionAlthough the circulating TH17 cell pool is expanded in patients with PMR, our findings indicate that TH1 cells are involved in the inflammation of bursae and tendon sheaths in this condition. Our study points towards the TH1 cell pathway as a potential target for therapy in PMR.

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“…Aging is a crucial element as PMR occurs in elderly patients. Aging may increase the susceptibility to infectious agents, immune responses, or the release of cytokines [5]. However, its pathogenesis has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

JAK signaling was involved in the pathogenesis of Polymyalgia Rheumatica

Yang

et al. 2022

Preprint

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Objectives. Polymyalgia Rheumatica (PMR) is a common inflammatory disease in elderly persons whose pathogenesis is unclear. We aimed to explore the pathogenetic features of PMR and find a new therapeutic strategy. Methods. We included 11 patients with PMR and 20 age-matched and sex-matched healthy controls (HC) in this study. The disease features were described. The gene expression profiles were analyzed in peripheral blood mononuclear cells (PBMCs) by RNA sequencing and were confirmed by RT-PCR. We also tested gene expression profiles in five patients with PMR after tofacitinib therapy. Results. Patients with PMR experienced pain with high disease activity scores. The gene expression of PBMCs in patients with PMR differed from that in HC by RNA sequencing. GO and KEGG analysis demonstrated that inflammatory response and cytokine-cytokine receptor interaction were the most remarkable pathways. There were markedly expanded IL6R, IL1B, IL1R1, JAK2, TLR2, TLR4, TLR8, CCR1, CR1, S100A8, S100A12, and IL17RA expressions. Those genes may trigger the JAK signaling. Furthermore, tofacitinib, a pan JAK inhibitor, effectively treated five patients with PMR, leading to clinical remission and a significant decrease in inflammatory genes. Conclusions. Many inflammatory genes associated with JAK signaling were increased in patients with PMR, suggesting an important role of JAK signaling in PMR disease development. JAK inhibitors may effectively treat PMR. Keywords: Polymyalgia Rheumatica, Inflammatory pathway, JAK signaling

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The pathophysiology of polymyalgia rheumatica, small pieces of a big puzzle

Cited by 36 publications

References 96 publications

Changes of Necroptosis in Irbesartan Medicated Cardioprotection in Diabetic Rats

Changes of Necroptosis in Irbesartan Medicated Cardioprotection in Diabetic Rats

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

JAK signaling was involved in the pathogenesis of Polymyalgia Rheumatica

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