ABSTRACT
Background: Vaccination is considered efficient in controlling infections incl. SARS-CoV-2. Prior studies showed that patients receiving rituximab (RTX) with low B cell counts are at increased infectious risk (1) and risk of inadequate vaccination responses (2, 3). Thus, the ability to further defne and predict vaccination responses in these patients may guide their optimal protection. Objectives: To assess predictive biomarkers of vaccination responses upon SARS-CoV-2 vaccination in RTX treated patients. Methods: B cell characteristics before vaccination were evaluated to predict responses in 15 patients with autoimmune infammatory rheumatic diseases receiving RTX. 11 patients with rheumatoid arthritis on other therapies (RA), 11 kidney transplant recipients (KTR) and 15 healthy volunteers (HC) served as controls. A multidimensional analysis of B cell subsets and a correlation matrix were performed to identify predictive biomarkers. Results: Signifcant differences regarding absolute B cell counts and specifc subset distribution pattern between the groups were validated at baseline. Here, the majority of B cells from vaccination responders of the RTX group (RTX IgG+) comprised naïve and transitional B cells, whereas vaccination non-responders (RTX IgG-) carried preferentially plasmablasts and double negative (CD27-IgD-) B cells (Figure 1). Moreover, there was a positive correlation between neutralizing antibodies and absolute B cell numbers with B cells expressing HLA-DR and CXCR5 (involved in antigen presentation and germinal center formation) as well as an inverse correlation with CD95 expression and CD21low expression (marker for activation and exhaustion) on B cells. Conclusion: Substantial repopulation of naïve B cells upon RTX therapy appears to be essential for an adequate vaccination response requiring germinal center formation. In contrast, expression of exhaustion markers (CD21low, CXCR5-, CD95+) indicate negative predictors of vaccination responses. These results may guide optimized vaccination strategies in RTX treated patients clearly requiring antigen-inexperienced B cells for appropriate protection.