Dezember 2023

Association between infection and the onset of giant cell arteritis and polymyalgia rheumatica: a systematic review and meta-analysis [1]

VASAS summary
Why some patients get autoimmune diseases, including vasculitis, is still not well understood. Besides genetic predisposition (in the case of GCA HLA-DR4), infections have been associated with different autoimmune diseases. The theory states that infections activate the immune system causing inflammation. Inflammation can accidentally also target healthy tissue. Such collateral damage can be mediated by unspecific immune cell activation (so-called ‘bystander activation’) or by a specific immune response against the pathogen that also recognizes proteins from the healthy cells due to similarities to pathogen-derived proteins (‘molecular mimicry’). To date, however, there is no conclusive evidence of whether infections in general or specific infections may trigger autoimmunity. In giant cell arteritis (GCA), several studies suggested a correlation between disease onset and herpes zoster, parainfluenza virus, or other infections.

A French group now performed a review and meta-analysis of the literature on infections and the onset of GCA (and polymyalgia rheumatica, PMR). The study found a significant and positive association between overall infections and the onset of GCA. This effect was consistent, but with only about 1.3 times increased risk, it was not very strong. Interestingly, the effect was only detectable when the infection occurred within the year before the GCA/PMR diagnosis was made and not if the infection was >12 months ago. Given that this data supports that infection and disease onset are time-related, this supports the hypothesis that any infection can be a potential trigger for GCA/PMR.

When looking at specific infections, a similar association was observed between GCA/PMR and herpes zoster infections. Interestingly, this association was regardless of the timing of the infection, suggesting that a Zoster might not be a trigger but a pre-existing condition potentially influencing GCA pathogenesis through cross-reactive T cells (‘molecular mimicry’). VASAS members and other research groups previously investigated this question studying GCA patients at diagnosis for the presence of Varicella Zoster Virus (VZV) specific and artery-specific T cells. We found no evidence for enhanced anti-Zoster or artery immunity compared to healthy controls (Bigler MB et al, Arthritis & Rheumatol. 2018). The link between infection may, therefore, be more complex than just molecular mimicry.

In summary, the meta-analysis further supports the role of infections in GCA. The study also highlights the need for further research to understand whether infections act as triggers of autoimmunity or are rather indicators of an age-related immune dysfunction contributing to GCA pathogenesis.

[1] Pacoureau L et al. Association between infection and the onset of giant cell arteritis and polymyalgia rheumatica: a systematic review and meta-analysis. RMD Open. 2023 Nov;9(4):e003493. doi: 10.1136/rmdopen-2023-003493.

Verfasst von
Prof. Dr. med. Christoph T. Berger
Senior Physician, Clinical Immunology
PI Translational Immunology
University Hospital Basel
December 2023

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