tetano
Editor, Senior Moderator
RMD Open
. 2025 Aug 4;11(3):e005724.
doi: 10.1136/rmdopen-2025-005724. TNF inhibitors affect the induction and maintenance of spike-specific B-cell responses after mRNA vaccination
Laura Yl Kummer[SUP] 1 2 [/SUP], Lisan H Kuijper[SUP] 1 [/SUP], Laura Fernández Blanco[SUP] 1 2 [/SUP], Amélie Bos[SUP] 1 [/SUP], Christine Kreher[SUP] 1 [/SUP], Niels Jm Verstegen[SUP] 1 [/SUP], Mariël C Duurland[SUP] 1 [/SUP], Veronique Al Konijn[SUP] 1 [/SUP], Tineke Jorritsma[SUP] 1 [/SUP], Maryse Tempert[SUP] 1 [/SUP], Charlotte Menage[SUP] 1 [/SUP], Maurice Steenhuis[SUP] 1 [/SUP], Marit J van Gils[SUP] 3 [/SUP], Mathieu Claireaux[SUP] 3 [/SUP], Juan J Garcia-Vallejo[SUP] 4 [/SUP], Geert Ram D'Haens[SUP] 5 [/SUP], Mark Löwenberg[SUP] 5 [/SUP], Adriaan G Volkers[SUP] 5 [/SUP], Koos Pj van Dam[SUP] 2 [/SUP], Eileen W Stalman[SUP] 2 [/SUP], Luuk Wieske[SUP] 2 6 [/SUP], Sander W Tas[SUP] 7 [/SUP], Laura Boekel[SUP] 8 [/SUP], Gertjan Wolbink[SUP] 1 8 [/SUP], Theo Rispens[SUP] 1 [/SUP], Taco W Kuijpers[SUP] 9 [/SUP], Filip Eftimov[SUP] 2 [/SUP], S Marieke van Ham[SUP] 1 10 [/SUP], Anja Ten Brinke[SUP] 11 [/SUP]
Affiliations
Objectives: Tumour necrosis factor inhibitors (TNFi) are widely used and effective as treatment for immune-mediated inflammatory diseases (IMIDs). However, TNFi therapy causes a faster waning of antibody responses following vaccination. The underlying cause by which TNFi affect humoral immunity remains to be elucidated. The formation of long-lasting, high-affinity antibodies after vaccination results from germinal centre (GC)-derived, T cell-dependent B-cell responses. Therefore, this study investigated how TNFi affect the formation and maintenance of antigen-specific B- and CD4+ T-cell responses following SARS-CoV-2 mRNA vaccination.
Methods: SARS-CoV-2 spike-specific B-cell responses were characterised using spectral flow cytometry. Spike-specific CD4+ T cells were measured using an activation-induced marker assay. 15 patients with inflammatory bowel disease (IBD) treated with TNFi were compared with 9 IBD patients without systemic immunosuppression and 10 healthy controls.
Results: Spike-specific CD4+T-cell frequency and phenotype, including T follicular helper cells, were not affected by TNFi. Total spike-specific B-cell frequencies were reduced in TNFi-treated patients. Deep phenotyping revealed lower IgG+memory B-cell frequencies in TNFi-treated patients 3-6 months after vaccination. These data were confirmed in TNFi-treated rheumatoid arthritis patients. Interestingly, already at day 7 after the second vaccination, TNFi therapy reduced the induction of class-switched CD11c- CD71+activated B cells, which are believed to be GC-derived. Conversely, CD11c+B cells, associated with extrafollicular B-cell responses, were not affected by TNFi therapy.
Conclusions: These data suggest that TNFi therapy affects the differentiation of GC-derived B cells, which may explain its effect on humoral immune responses.
Keywords: Autoimmune Diseases; B-Lymphocytes; T-Lymphocytes; Tumor Necrosis Factor Inhibitors; Vaccination.
. 2025 Aug 4;11(3):e005724.
doi: 10.1136/rmdopen-2025-005724. TNF inhibitors affect the induction and maintenance of spike-specific B-cell responses after mRNA vaccination
Laura Yl Kummer[SUP] 1 2 [/SUP], Lisan H Kuijper[SUP] 1 [/SUP], Laura Fernández Blanco[SUP] 1 2 [/SUP], Amélie Bos[SUP] 1 [/SUP], Christine Kreher[SUP] 1 [/SUP], Niels Jm Verstegen[SUP] 1 [/SUP], Mariël C Duurland[SUP] 1 [/SUP], Veronique Al Konijn[SUP] 1 [/SUP], Tineke Jorritsma[SUP] 1 [/SUP], Maryse Tempert[SUP] 1 [/SUP], Charlotte Menage[SUP] 1 [/SUP], Maurice Steenhuis[SUP] 1 [/SUP], Marit J van Gils[SUP] 3 [/SUP], Mathieu Claireaux[SUP] 3 [/SUP], Juan J Garcia-Vallejo[SUP] 4 [/SUP], Geert Ram D'Haens[SUP] 5 [/SUP], Mark Löwenberg[SUP] 5 [/SUP], Adriaan G Volkers[SUP] 5 [/SUP], Koos Pj van Dam[SUP] 2 [/SUP], Eileen W Stalman[SUP] 2 [/SUP], Luuk Wieske[SUP] 2 6 [/SUP], Sander W Tas[SUP] 7 [/SUP], Laura Boekel[SUP] 8 [/SUP], Gertjan Wolbink[SUP] 1 8 [/SUP], Theo Rispens[SUP] 1 [/SUP], Taco W Kuijpers[SUP] 9 [/SUP], Filip Eftimov[SUP] 2 [/SUP], S Marieke van Ham[SUP] 1 10 [/SUP], Anja Ten Brinke[SUP] 11 [/SUP]
Affiliations
- PMID: 40759563
- DOI: 10.1136/rmdopen-2025-005724
Objectives: Tumour necrosis factor inhibitors (TNFi) are widely used and effective as treatment for immune-mediated inflammatory diseases (IMIDs). However, TNFi therapy causes a faster waning of antibody responses following vaccination. The underlying cause by which TNFi affect humoral immunity remains to be elucidated. The formation of long-lasting, high-affinity antibodies after vaccination results from germinal centre (GC)-derived, T cell-dependent B-cell responses. Therefore, this study investigated how TNFi affect the formation and maintenance of antigen-specific B- and CD4+ T-cell responses following SARS-CoV-2 mRNA vaccination.
Methods: SARS-CoV-2 spike-specific B-cell responses were characterised using spectral flow cytometry. Spike-specific CD4+ T cells were measured using an activation-induced marker assay. 15 patients with inflammatory bowel disease (IBD) treated with TNFi were compared with 9 IBD patients without systemic immunosuppression and 10 healthy controls.
Results: Spike-specific CD4+T-cell frequency and phenotype, including T follicular helper cells, were not affected by TNFi. Total spike-specific B-cell frequencies were reduced in TNFi-treated patients. Deep phenotyping revealed lower IgG+memory B-cell frequencies in TNFi-treated patients 3-6 months after vaccination. These data were confirmed in TNFi-treated rheumatoid arthritis patients. Interestingly, already at day 7 after the second vaccination, TNFi therapy reduced the induction of class-switched CD11c- CD71+activated B cells, which are believed to be GC-derived. Conversely, CD11c+B cells, associated with extrafollicular B-cell responses, were not affected by TNFi therapy.
Conclusions: These data suggest that TNFi therapy affects the differentiation of GC-derived B cells, which may explain its effect on humoral immune responses.
Keywords: Autoimmune Diseases; B-Lymphocytes; T-Lymphocytes; Tumor Necrosis Factor Inhibitors; Vaccination.