Causal relationship between 731 immune cell immunophenotypes and giant cell arteritis: a Mendelian randomisation study.

Abstract

Objectives: Giant cell arteritis (GCA) is the most common form of vasculitis among adults aged 50 and over, characterised by systemic inflammation and the potential for severe complications such as blindness and stroke. Despite its prevalence, the aetiology of GCA remains incompletely understood, with current treatments largely relying on corticosteroids, which carry significant side effects.

Methods: Our study utilised a bilateral Mendelian randomisation (MR) approach to investigate the causal impact of immune cells on GCA. By analysing 731 immune cell phenotypes from genome-wide association studies (GWAS) data of 3,757 European individuals, we aimed to identify genetic variants as instrumental variables for immune cell traits, thereby elucidating their role in GCA susceptibility. To ensure a robust examination, we used various MR techniques, including the inverse-variance weighted (IVW) method, and carried out sensitivity analyses to assess the dependability of our findings.

Results: Forward MR analysis identified three immune traits with significant associations with GCA: a protective effect from the absolute count of monocytic myeloid-derived suppressor cells and increased risks associated with HLA DR expression on CD14+ CD16-, and CD14+ monocytes. The sensitivity analyses yielded results consistent with the main findings. The reverse MR analysis yielded no statistically significant results.

Conclusions: The study advances our understanding of the immunological underpinnings of GCA, suggesting that specific immune cells significantly influence the disease's development. These insights pave the way for the exploration of new therapeutic targets that could offer more targeted and tolerable treatment options beyond the current reliance on corticosteroids. Further research is needed to validate these potential biomarkers and therapeutic targets in clinical settings.