TNF inhibitors affect the induction and maintenance of spike-specific B-cell responses after mRNA vaccination
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 remai...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2025-08-01
|
| Series: | RMD Open |
| Online Access: | https://rmdopen.bmj.com/content/11/3/e005724.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849684187526725632 |
|---|---|
| author | Sander W Tas Taco W Kuijpers Gertjan Wolbink Theo Rispens Anja Ten Brinke Juan J Garcia-Vallejo S Marieke van Ham Mark Löwenberg Luuk Wieske Laura Boekel Filip Eftimov Eileen W Stalman Maurice Steenhuis Adriaan G Volkers Christine Kreher Lisan H Kuijper Mariël C Duurland Laura Fernández Blanco Amélie Bos Charlotte Menage Tineke Jorritsma Marit J van Gils Mathieu Claireaux Geert RAM D’Haens Laura YL Kummer Niels JM Verstegen Veronique AL Konijn Maryse Tempert Koos PJ van Dam |
| author_facet | Sander W Tas Taco W Kuijpers Gertjan Wolbink Theo Rispens Anja Ten Brinke Juan J Garcia-Vallejo S Marieke van Ham Mark Löwenberg Luuk Wieske Laura Boekel Filip Eftimov Eileen W Stalman Maurice Steenhuis Adriaan G Volkers Christine Kreher Lisan H Kuijper Mariël C Duurland Laura Fernández Blanco Amélie Bos Charlotte Menage Tineke Jorritsma Marit J van Gils Mathieu Claireaux Geert RAM D’Haens Laura YL Kummer Niels JM Verstegen Veronique AL Konijn Maryse Tempert Koos PJ van Dam |
| author_sort | Sander W Tas |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c97f8b30e3ea4f2da72c87381881bdc2 |
| institution | DOAJ |
| issn | 2056-5933 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | RMD Open |
| spelling | doaj-art-c97f8b30e3ea4f2da72c87381881bdc22025-08-20T03:23:33ZengBMJ Publishing GroupRMD Open2056-59332025-08-0111310.1136/rmdopen-2025-005724TNF inhibitors affect the induction and maintenance of spike-specific B-cell responses after mRNA vaccinationSander W Tas0Taco W Kuijpers1Gertjan Wolbink2Theo Rispens3Anja Ten Brinke4Juan J Garcia-Vallejo5S Marieke van Ham6Mark Löwenberg7Luuk Wieske8Laura Boekel9Filip Eftimov10Eileen W Stalman11Maurice Steenhuis12Adriaan G Volkers13Christine Kreher14Lisan H Kuijper15Mariël C Duurland16Laura Fernández Blanco17Amélie Bos18Charlotte Menage19Tineke Jorritsma20Marit J van Gils21Mathieu Claireaux22Geert RAM D’Haens23Laura YL Kummer24Niels JM Verstegen25Veronique AL Konijn26Maryse Tempert27Koos PJ van Dam28Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and Immunology Center, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Pediatric Immunology, Amsterdam UMC Location AMC, Amsterdam, the NetherlandsSanquin Research, Amsterdam, the NetherlandsSanquin Research, Amsterdam, the NetherlandsSanquin Research, Amsterdam, the NetherlandsDepartment of Molecular Cell Biology and Immunology, Amsterdam UMC Location VUmc, Amsterdam, the NetherlandsSanquin Research, Amsterdam, the NetherlandsDepartment of Gasteroenterology, Amsterdam UMC Location AMC, Amsterdam, the NetherlandsDepartment of Neurology and Neurophysiology, Amsterdam UMC Location AMC, Amsterdam, the NetherlandsAmsterdam Rheumatology and Immunology Center, Reade, Amsterdam, the NetherlandsDepartment of Neurology and Neurophysiology, Amsterdam UMC Location AMC, Amsterdam, the NetherlandsDepartment of Neurology and Neurophysiology, Amsterdam UMC Location AMC, Amsterdam, the NetherlandsSanquin Research, Amsterdam, the NetherlandsDepartment of Gasteroenterology, Amsterdam UMC Location AMC, Amsterdam, the NetherlandsSanquin Research, Amsterdam, the NetherlandsSanquin Research, Amsterdam, the NetherlandsSanquin Research, Amsterdam, the NetherlandsSanquin Research, Amsterdam, the NetherlandsSanquin Research, Amsterdam, the NetherlandsSanquin Research, Amsterdam, the NetherlandsSanquin Research, Amsterdam, the NetherlandsDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC Location VUmc, Amsterdam, the NetherlandsDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC Location VUmc, Amsterdam, the NetherlandsDepartment of Gasteroenterology, Amsterdam UMC Location AMC, Amsterdam, the NetherlandsSanquin Research, Amsterdam, the NetherlandsSanquin Research, Amsterdam, the NetherlandsSanquin Research, Amsterdam, the NetherlandsSanquin Research, Amsterdam, the NetherlandsDepartment of Neurology and Neurophysiology, Amsterdam UMC Location AMC, Amsterdam, the NetherlandsObjectives 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.https://rmdopen.bmj.com/content/11/3/e005724.full |
| spellingShingle | Sander W Tas Taco W Kuijpers Gertjan Wolbink Theo Rispens Anja Ten Brinke Juan J Garcia-Vallejo S Marieke van Ham Mark Löwenberg Luuk Wieske Laura Boekel Filip Eftimov Eileen W Stalman Maurice Steenhuis Adriaan G Volkers Christine Kreher Lisan H Kuijper Mariël C Duurland Laura Fernández Blanco Amélie Bos Charlotte Menage Tineke Jorritsma Marit J van Gils Mathieu Claireaux Geert RAM D’Haens Laura YL Kummer Niels JM Verstegen Veronique AL Konijn Maryse Tempert Koos PJ van Dam TNF inhibitors affect the induction and maintenance of spike-specific B-cell responses after mRNA vaccination RMD Open |
| title | TNF inhibitors affect the induction and maintenance of spike-specific B-cell responses after mRNA vaccination |
| title_full | TNF inhibitors affect the induction and maintenance of spike-specific B-cell responses after mRNA vaccination |
| title_fullStr | TNF inhibitors affect the induction and maintenance of spike-specific B-cell responses after mRNA vaccination |
| title_full_unstemmed | TNF inhibitors affect the induction and maintenance of spike-specific B-cell responses after mRNA vaccination |
| title_short | TNF inhibitors affect the induction and maintenance of spike-specific B-cell responses after mRNA vaccination |
| title_sort | tnf inhibitors affect the induction and maintenance of spike specific b cell responses after mrna vaccination |
| url | https://rmdopen.bmj.com/content/11/3/e005724.full |
| work_keys_str_mv | AT sanderwtas tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT tacowkuijpers tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT gertjanwolbink tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT theorispens tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT anjatenbrinke tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT juanjgarciavallejo tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT smariekevanham tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT marklowenberg tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT luukwieske tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT lauraboekel tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT filipeftimov tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT eileenwstalman tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT mauricesteenhuis tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT adriaangvolkers tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT christinekreher tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT lisanhkuijper tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT marielcduurland tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT laurafernandezblanco tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT ameliebos tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT charlottemenage tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT tinekejorritsma tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT maritjvangils tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT mathieuclaireaux tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT geertramdhaens tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT lauraylkummer tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT nielsjmverstegen tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT veroniquealkonijn tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT marysetempert tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination AT koospjvandam tnfinhibitorsaffecttheinductionandmaintenanceofspikespecificbcellresponsesaftermrnavaccination |