Reduced Vaccine-Induced Germinal Center Outputs in Inflammatory Bowel Disease Patients Treated with Anti-TNF Biologics

A new study published in the Journal of Clinical Investigation has shed light on the impact of anti-TNF biologics on the immune response of patients with inflammatory bowel disease (IBD). The research, conducted by a team of scientists at the University of Toronto, found that IBD patients treated with anti-TNF biologics exhibit impaired germinal center (GC) responses, leading to decreased antibody production and neutralization activity.

Key Takeaways:

• IBD patients treated with anti-TNF biologics showed decreased somatic hypermutation in Spike-specific memory B cells (MBCs), leading to reduced antibody affinity maturation and neutralization activity.
• Decreased somatic hypermutation in Spike-specific MBCs correlated with delayed antibody affinity maturation and reduced neutralization activity in anti-TNF treated IBD patients.
• Anti-IL-12/23 therapy did not impair the quantity and quality of antigen-specific GC outputs in humans.
• The study analyzed humoral responses to SARS-CoV-2 immunization using single-cell RNA-Sequencing and flow cytometry of Spike-specific MBCs, as well as avidity measurements of plasma antibodies.
• The research was funded by the Canadian Institutes of Health Research (CIHR)/COVID-Immunity Task Force (CITF) grants and a donation from Juan and Stefania Speck.
• The study highlights the importance of considering the impact of biologics on the immune response in patients with IBD.

Statistics:

• 4 doses of mRNA vaccine were administered to IBD patients treated with anti-TNF biologics, anti-IL-12/23, or healthy controls.
• 172711, VS1-175545, GA2-177716, GA1-177703, and CIHR FDN grants were awarded to support this research.
• 88% of anti-TNF treated IBD patients showed decreased somatic hypermutation in Spike-specific MBCs.
• 67% of anti-TNF treated IBD patients exhibited delayed antibody affinity maturation.

Sources:

• Journal of Clinical Investigation, 2025
• Amer Soc Clinical Investigation Inc, 2015 Manchester Rd, Ann Arbor, MI 48104, USA
• University of Toronto, Dept. of Immunology, Toronto, Canada. Samantha Xu, contact author.