Reduced vaccine-induced germinal center outputs in patients with inflammatory bowel disease treated with anti-TNF biologics.
prospective_cohort · Level II
Where this comes from
- Record sourced from PubMed, PMID 40728886.
- Also identified by DOI 10.1172/JCI192589 and PMC identifier 12483611.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
BACKGROUNDAnti-TNF biologics are widely used to treat patients with immune-mediated inflammatory diseases. In mouse models, the complete absence of TNF impairs germinal center (GC) responses. Less is known about the impact of anti-TNF therapy on specific immune responses in humans. Widespread vaccination against SARS-CoV-2 offered an unprecedented opportunity to investigate the effects of biological therapies on responses to specific immunization. Previous work demonstrated that patients with inflammatory bowel disease (IBD) who were treated with anti-TNF biologics exhibited decreased Spike-specific antibody responses compared with patients with IBD treated with anti-IL-12/23 or healthy controls, even after 4 doses of mRNA vaccine.METHODSHere we analyzed humoral responses to SARS-CoV-2 immunization using single-cell RNA-Sequencing and flow cytometry of Spike-specific memory B cells (MBC), as well as avidity measurements of plasma antibodies from patients with IBD treated with anti-TNF or anti-IL-12/23 and from people in the healthy control group.RESULTSWe observed decreased somatic hypermutation in the B cell receptors of Spike-specific MBCs and decreased antigen-specific MBC accumulation following SARS-CoV-2 mRNA vaccination in patients with IBD treated with anti-TNF, compared with patients with IBD treated with anti-IL-12/23 or people in the healthy control group. This decreased somatic hypermutation in Spike-specific MBCs in patients treated with anti-TNF correlated with decreased and delayed antibody affinity maturation and reduced neutralization activity.CONCLUSIONThese data provide in vivo evidence that anti-TNF, but not anti-IL-12/23, therapy impairs the quantity and quality of antigen-specific GC outputs in humans.FUNDINGJuan and Stefania Speck (donation) and by Canadian Institutes of Health Research (CIHR)/COVID-Immunity Task Force (CITF) grants VR-1 172711, VS1-175545, GA2-177716, GA1-177703 and CIHR FDN 143301 &143350.
Medical subject headings
- Inflammatory Bowel Diseases
- SARS-CoV-2
- Germinal Center
- COVID-19
- COVID-19 Vaccines
- Tumor Necrosis Factor-alpha
- Tumor Necrosis Factor Inhibitors