B Cell Characteristics at Baseline Predict Vaccination Response in RTX Treated Patients

Abstract

BackgroundVaccination is considered as most efficient strategy in controlling SARS-CoV-2 pandemic spread. Nevertheless, patients with autoimmune inflammatory rheumatic diseases receiving rituximab (RTX) are at increased risk to fail humoral and cellular responses upon vaccination. The ability to predict vaccination responses is essential to guide adequate safety and optimal protection in these patients.MethodsB- and T- cell data before vaccination were evaluated for characteristics predicting vaccine responses in altogether 15 patients with autoimmune inflammatory rheumatic diseases receiving RTX. Eleven patients with rheumatoid arthritis (RA) on other therapies, 11 kidney transplant recipients (KTR) on regular immunosuppression and 15 healthy controls (HC) served as controls. A multidimensional analysis of B cell subsets via UMAP algorithm and a correlation matrix were performed in order to identify predictive markers of response in patients under RTX therapy.ResultsSignificant differences regarding absolute B cell counts and specific subset distribution pattern between the groups were identified at baseline. In this context, the majority of B cells from vaccination responders of the RTX group (RTX IgG+) were naïve and transitional B cells, whereas vaccination non-responders (RTX IgG-) carried preferentially plasmablasts and double negative (CD27-IgD-) B cells. Moreover, there was a positive correlation between neutralizing antibodies and B cells expressing HLA-DR and CXCR5 as well as an inverse correlation with CD95 expression and CD21low expression by B cells among vaccination responders.SummarySubstantial repopulation of the naïve B cell compartment after RTX therapy appeared to be essential for an adequate vaccination response, which seem to require the additional capability of antigen presentation and germinal center formation. Moreover, expression of exhaustion markers represent negative predictors of vaccination responses.

Persistent but atypical germinal center reaction among 3rd SARS-CoV-2 vaccination after rituximab exposure

“…All participants gave written informed consent according to the approval of the ethics committee at the CharitéUniversity Hospital Berlin (EA2/010/21, EA4/188/20). Humoral vaccine response at d28 and d42 (Figures 2A, C), cellular data at d0 and d28 for total B cells, (Figure 3A), antigen specific (RBD+) B cells (Figures 3D, E) and at d28 for antigen specific T cells Figures 5A, C, D) have been partially previously published (15,17).…”

“…The blocking ELISA GenScript qualitatively detects anti-SARS-CoV-2 antibodies suppressing the interaction between the receptor binding domain (RBD) of the viral spike glycoprotein (S) and the angiotensin-converting enzyme 2 (ACE2) protein on the surface of cells, as described ( 17 ). Scores < 30% were considered negative, scores ≥ 30% were considered positive (linear quantitative range).…”

“…RTX treated outpatients, who participated at our initial vaccination study (15) were screened for RTX treatment after the second vaccination. We identified 7 patients with rheumatoid arthritis [RA, according 2010 ACR Rheumatoid Arthritis Classification Criteria (16)], who received another course of RTX (1-2mg) treatment 1-2 months after the second SARS-CoV-2 vaccination.…”

“…In this study we addressed the question about durability of vaccination-induced SARS-CoV-2 immune responses and induction of a secondary immune response in the context of restricted B cell availability upon rituximab re-exposure. Therefore, we assessed humoral as well as B and T cellular vaccination responses upon 3rd vaccination in RTX treated patients who initially mounted anti-spike SARS-CoV-2 IgG antibodies upon primary 2x vaccination (15) and got re-exposed to RTX 1-2 months after the second vaccination. As control for known long-lived induced immunity, we analyzed steady-state humoral and cellular tetanus toxoid (TT) immune responses.…”

Multiple effects of TNFα inhibitors on the development of the adaptive immune response after SARS-CoV-2 vaccination

“…and T cells during SARS-CoV-2 vaccination is not fully understood, as humoral and T cell immunity appear to depend on B cell counts before vaccination. (6) In addition, data from immunocompromised kidney transplant patients show that T cell activity after vaccination correlates with the magnitude of the antibody response, (7) while high T cell activity has been observed in B cell depleted patients after immunisation. (8) Sera from vaccinated healthy individuals show only limited neutralisation capacity against Omicron (B.1.1.529) VOC.…”