Evidence map›Paper›PMID 40728886›Full record

ArticleThe Journal of clinical investigation2025

Reduced vaccine-induced germinal center outputs in patients with inflammatory bowel disease treated with anti-TNF biologics.

Michelle W Cheung, Samantha Xu, Janna R Shapiro, Freda Qi, Melanie Delgado-Brand, Karen Colwill, Roya M Dayam, Ying Liu, Jenny D Lee, Joanne M Stempak and 5 more

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Michelle W CheungDepartment of Immunology, University of Toronto, Toronto, Ontario, Canada.
Samantha XuDepartment of Immunology, University of Toronto, Toronto, Ontario, Canada.
Janna R ShapiroDepartment of Immunology, University of Toronto, Toronto, Ontario, Canada.
Freda QiLunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada.
Melanie Delgado-BrandLunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada.
Karen ColwillLunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada.
Roya M DayamLunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada.
Ying LiuDepartment of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Jenny D LeeLunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada.
Joanne M StempakLunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada.
James M RiniDepartment of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Vinod ChandranGladman Krembil Psoriatic Arthritis Research Program, Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Mark S SilverbergLunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada.
Anne-Claude GingrasLunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada.
Tania H WattsDepartment of Immunology, University of Toronto, Toronto, Ontario, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

COVID-19COVID-19 VaccinesGerminal CenterInflammatory Bowel DiseasesSARS-CoV-2Tumor Necrosis Factor-alphaTumor Necrosis Factor InhibitorsAdultAntibodies, ViralFemaleHumansMaleMemory B CellsMiddle AgedSpike Glycoprotein, CoronavirusAntibodies, ViralCOVID-19 VaccinesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Tumor Necrosis Factor-alphaTumor Necrosis Factor InhibitorsAdaptive immunityImmunologyInfectious diseaseVaccines

Identifiers

PMID40728886
PMCPMC12483611

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.