An Observational Study of the Impact of Systemic B-cell Depletion on Cervicovaginal Mucosal Environment

Importance: Emerging data show that B-cell depleting chemotherapies, which are increasingly used to treat autoimmune disorders and multiple sclerosis, can be associated with mucosal side effects such as inflammatory vaginitis. Objective: Evaluate the impact of rituximab treatment on vaginal mucosal immune markers, endocervical immune cell populations and vaginal microbiome. Design: Cross-sectional observational study conducted between 2022 - 2024. Setting: Academic medical center, Boston Massachusetts. Participants: We enrolled women aged >18 years who were either 1) receiving rituximab for autoimmune renal disease or were 2) healthy controls. Exposure: Treatment with rituximab, an anti CD20 monoclonal antibody. Main outcome and measure: We compared endocervical immune cell populations, vaginal fluid immune markers, vaginal fluid immunoglobulins and vaginal microbiome composition between individuals being treated with rituximab and healthy controls. Results: pattern of vaginal microbiota was more common in the rituximab group. Conclusions and Relevance: Systemic B-cell depletion is associated with reduced vaginal fluid IgA, a more diverse microbiome composition, and increases in many vaginal fluid immune markers compared to healthy controls. The reduction in vaginal fluid IgA may provide opportunities for vaginal bacteria to induce inflammation. Key points: Systemic B cell depletion is associated with alterations in vaginal mucosal immune markers and microbiome composition which increase local inflammation.