The pathophysiology of polymyalgia rheumatica

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

Author links open overlay panelGuillermo CarvajalAlegriaabSaraBoukhlalacDiviCornecabValérieDevauchelle-Pensecab

a

Univ Brest, Inserm, CHU de Brest, LBAI, UMR1227, Brest, France

b

Service de Rhumatologie, Centre de Référence Maladies Autoimmunes Rares CERAINO, CHU Cavale Blanche, Brest, France

c

Service de Médecine Interne, Pneumologie, Médecine Vasculaire, CHU Cavale Blanche, Brest, France

Received 17 April 2020, Accepted 23 April 2020, Available online 15 September 2020.

https://doi.org/10.1016/j.autrev.2020.102670Get rights and content

Highlights

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Most of the findings about PMR pathophysiology come from blood sample analysis. Few synovial biopsy studies are available and suggest different implications for immune system actors.

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Lymphocyte subsets are modified in PMR patients, but their role in its pathophysiology is not fully understood. These modifications might be secondary to chronic inflammation.

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Inflammatory cytokines such as IL-6, TNFα and IL-1 are increased in muscle and synovial fluid, but only IL-6 is increased in serum.

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Aging of the immune system might play a role in PMR pathophysiology, but little data are available thus far.

Abstract

Polymyalgia rheumatica (PMR) is a frequent rheumatic condition among people over 50 years of age. Despite its frequent association with giant cell arteritis (GCA), PMR can be isolated. Its pathophysiology is poorly understood. Nevertheless, many studies are ongoing; 98 studies are currently referenced in ClinicalTrials.org involving several conventional and targeted therapies. In this review, we synthetize the current knowledge about PMR pathophysiology according to genetic and immunogenetic, immunologic, antibody and aging data. Immunogenetic data are mainly related to the HLA system and the association between the HLA-DRB1 and PMR. Few studies are also about immunogenetics of proinflammatory interleukins (i.e. IL-6). The decrease of CD8+Tcells and the strong increase of IL-6 where the main elements of PMR's pathophysiology until the recent years. The disturbance of B cell homeostasis, the search for IL-6 secretion by the innate immune system, the role of aging, are new elements revealed by recent studies. Aging might be a key element to consider as PMR occurs in patients over 50 years of age. Aging may act by the increased susceptibility to infections, by immunological modifications or hormonal disturbances. The role of the cellular infiltration around the joints remains a crucial question. Only a handful of studies described this infiltration. Finally, this review reveals the gaps in available data and suggests new leads and in-depth studies for further research on PMR pathophysiology.

Keywords

Polymyalgia rheumaticaHLA-DRT cellB cellInterleukin-6Aging

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