Mejia Marlyd E, Bowman Savannah, Lee Jessica, El-Halwagi Ali, Ferguson Keshia, Maliekel Maryjo, Zhou Yixuan, Serchejian Camille, Robertson Clare M, Ballard Mallory B, Lu Lee B, Khan Sobia, Oladunjoye Olubunmi O, Huang Shixia, Agarwal Sandeep K, Patras Kathryn A
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
Section of Immunology, Allergy, and Rheumatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
medRxiv. 2025 Apr 13:2025.04.11.25325692. doi: 10.1101/2025.04.11.25325692.
The human microbiota is implicated in the development and progression of rheumatoid arthritis (RA). Given the increased RA burden in women, and well-known correlations between the vaginal microbiota and local inflammation, we seek to understand the vaginal microenvironment in the context of RA pathology.
Self-collected vaginal swabs and questionnaires on dietary and health practices were obtained from 36 RA and 50 demographically-matched control women, 18-63 years of age. Additionally, medication regimen and disease activity and severity were captured for the RA cohort. Vaginal swabs were subjected to full-length 16S rRNA gene sequencing, multiplex cytokine analyses, and quantification of rheumatoid factor, c-reactive protein, and anti-citrullinated protein antibodies (ACPAs).
Vaginal microbial richness and genera and , among other rare taxa, were elevated in RA versus control samples. Vaginal IL-18 and EGF levels were increased in the RA group; IL-18 correlated with multiple microbial features whereas EGF levels were not associated with bacterial composition or other host factors. Within the RA cohort, decreased relative abundance of was associated with joint pathologies, and was lower in individuals with serum detection of ACPAs and rheumatoid factor. Vaginal ACPAs were higher in the RA group and positively correlated with and multiple vaginal inflammatory cytokines.
We describe vaginal microbial and immunological differences in women with RA, particularly when accounting for diet and menopausal status, disease activity and severity, and medication use. This work opens a new avenue in the multidisciplinary approach to RA patient care.
人类微生物群与类风湿性关节炎(RA)的发生和发展有关。鉴于女性中RA负担的增加,以及阴道微生物群与局部炎症之间众所周知的相关性,我们试图在RA病理学背景下了解阴道微环境。
从36名年龄在18至63岁之间的RA女性和50名人口统计学匹配的对照女性中收集自我采集的阴道拭子以及关于饮食和健康习惯的问卷。此外,还记录了RA队列的用药方案、疾病活动度和严重程度。对阴道拭子进行全长16S rRNA基因测序、多重细胞因子分析以及类风湿因子、C反应蛋白和抗瓜氨酸化蛋白抗体(ACPA)的定量分析。
与对照样本相比,RA样本中阴道微生物丰富度以及某些属(包括罕见分类群)有所升高。RA组中阴道IL-18和EGF水平升高;IL-18与多种微生物特征相关,而EGF水平与细菌组成或其他宿主因素无关。在RA队列中,某属相对丰度的降低与关节病变有关,在血清检测到ACPA和类风湿因子的个体中该属含量较低。RA组中阴道ACPA水平较高,且与某属及多种阴道炎症细胞因子呈正相关。
我们描述了RA女性的阴道微生物和免疫学差异,尤其是在考虑饮食和绝经状态、疾病活动度和严重程度以及用药情况时。这项工作为RA患者护理的多学科方法开辟了一条新途径。