Study finds senescence pathways in the pathophysiology of giant cell arteritis

Analysis of patient tissue samples suggested that senescence pathways are implicated in giant cell arteritis (GCA). The biopsy samples revealed increased expression of the senescence-related proteins interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), both known targets for GCA therapy. These findings were published by researchers in Arthritis & Rheumatology.

William Jiemy and associates observed increased expression of p16 and p21 proteins,  drivers of cellular senescence, in temporal artery biopsy samples of GCA patients than the age-matched controls. According to earlier studies, these mechanisms accelerate cellular aging as shown by short telomeres and decreased normal function. The temporal artery biopsies (TABs) of individuals with GCA had higher levels of p16, p21, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Although p21 and p16 expression was observed in all three layers of the arteries, cells expressing p16 and p21 were primarily found near the internal elastic lamina, particularly among giant cells and macrophages. T cells occasionally expressed p16 and p21, but not B cells. Cells expressing GM-CSF/IL-6 and p16+ and p21+ were found throughout the TABs.

A 2021 study proposed a model for GCA in which circulating abnormally activated cells, particularly monocytes and CD4+ T cells, enter arteries in response to an unidentified stimulus and work together to destroy the vessel. Experts have also reviewed the evidence on the pathologic mechanism of the active disease and the treatment-related changes. Recent developments in diagnostic imaging have allowed the distinction between the classic cranial and large vessel (LV) GCA by demonstrating a greater degree of large vessel involvement than previously recognized. GCA shares characteristics with Takayasu arteritis and the more recently reported clinically isolated aortitis, two non-infectious granulomatous vasculitides that affect the aorta, and the poorly understood inflammatory arthritis/bursitis syndrome polymyalgia rheumatica. 

These findings highlight the need for further investigation into the role of senescence in the pathophysiology of GCA and suggest the presence of active senescence pathways at the site of vascular inflammation in GCA. The study opens up potential avenues for future research aimed at developing novel therapeutic interventions targeting senescence pathways in GCA.

References

  1. Jiemy WF, van Sleen Y, Graver JC, Pringle S, Brouwer E, van der Geest K, Cornec D, Boots AM, Sandovici M. Indication of activated senescence pathways in the temporal arteries of patients with giant cell arteritis. Arthritis & Rheumatology (Hoboken, NJ). 2023 Apr 14.
  2. Robinette ML, Rao DA, Monach PA. The immunopathology of giant cell arteritis across disease spectra. Frontiers in Immunology. 2021 Feb 25;12:623716.
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