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

Tumor necrosis factor (TNF) blocking agents are widely used to treat patients with immune-mediated inflammatory diseases. The complete absence of TNF in mice impairs germinal center responses. Less is known about the impact of anti-TNF therapy on specific immune responses in humans. The widespread vaccination against SARS-CoV-2 offered an unprecedented opportunity to investigate the effects of biological therapies on the response to a specific immunization. Previous work demonstrated that inflammatory bowel disease (IBD) patients treated with anti-TNF agents exhibit decreased Spike (S)-specific antibody responses compared to IBD patients treated with anti-IL-12/23 or healthy controls, even after four doses of mRNA vaccine. Here, we performed immune profiling of S-specific memory B cells (MBCs) isolated from anti-TNF treated- or anti-IL-12/23- treated IBD patients and healthy controls via 5' single cell RNA-sequencing, CITE-sequencing, and BCR-sequencing, to examine the transcriptome of and breadth of memory B cell responses to SARS-CoV-2 mRNA vaccination. This study provided in vivo evidence that anti-TNF, but not anti-IL-12/23, therapy impairs the quantity of and quality of antigen-specific germinal center outputs in humans.