Liu Qiong, Liu Xiaofang, Gao Mengge, Yang Bo, Luo Miaoqing, Yang Biying, Liang Guojun
Department of Clinical Nutrition, Huadu District People's Hospital of Guangzhou, Guangdong, China.
First Affiliated Hospital of Guangzhou Medical University, Guangdong, China.
Clin Exp Rheumatol. 2025 Apr;43(4):621-629. doi: 10.55563/clinexprheumatol/bnjlz9. Epub 2025 Mar 18.
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.
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.
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.
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.
巨细胞动脉炎（GCA）是50岁及以上成年人中最常见的血管炎形式，其特征为全身炎症以及存在失明和中风等严重并发症的可能性。尽管其发病率较高，但GCA的病因仍未完全明确，目前的治疗主要依赖糖皮质激素，而糖皮质激素具有显著的副作用。
我们的研究采用双侧孟德尔随机化（MR）方法来研究免疫细胞对GCA的因果影响。通过分析来自3757名欧洲个体的全基因组关联研究（GWAS）数据中的731种免疫细胞表型，我们旨在确定基因变异作为免疫细胞特征的工具变量，从而阐明它们在GCA易感性中的作用。为确保进行稳健的检验，我们使用了各种MR技术，包括逆方差加权（IVW）方法，并进行了敏感性分析以评估我们研究结果的可靠性。
正向MR分析确定了三种与GCA有显著关联的免疫特征：单核细胞来源的髓系抑制细胞绝对计数具有保护作用，以及CD14+ CD16-和CD14+单核细胞上HLA DR表达增加会带来风险。敏感性分析得出的结果与主要发现一致。反向MR分析未得出具有统计学意义的结果。
该研究增进了我们对GCA免疫基础的理解，表明特定免疫细胞对该疾病的发展有显著影响。这些见解为探索新的治疗靶点铺平了道路，有望提供超越目前对糖皮质激素依赖的更具针对性和耐受性的治疗选择。需要进一步研究以在临床环境中验证这些潜在的生物标志物和治疗靶点。
