Prinzensteiner, M. | bioRxiv Science

bioRxiv2026

Systemic antibody repertoires target specific microbial antigens in patients with colorectal cancer

Colorectal cancer (CRC) represents the third leading cause of cancer related deaths worldwide and is influenced by multiple risk factors. Both exposure to microbiota as well as adaptive immune responses have been implicated in CRC development and suggested as candidate biomarkers. However, the extent to which CRC and adenomas associate with systemic immune signatures against microbes remains unclear. Here, we apply Phage-display ImmunoPrecipitation Sequencing (PhIP-Seq) on 321 individuals of an Austrian CORSA cohort (Colorectal Cancer Study of Austria) including controls, adenomas, and CRC patients. Although antibody repertoires showed global similarity across the different disease status and limited predictive performance, prevalence-based analyses revealed specific signals, such as Helicobacter pylori CagY as candidate marker of CRC and viral antigens as candidate for non-cancer stages. Taken together, this large-scale analysis of antibody reactivity in CRC highlights the potential of serological markers to reflect disease-associated immune signatures.

immunology↗

bioRxiv2025

Mapping adaptive immune responses toward fungal antigens in inflammatory bowel disease using T cell repertoire sequencing and phage-immunoprecipitation sequencing

Inflammatory bowel disease (IBD) is an idiopathic, immune-mediated chronic inflammatory disease of the gut with two primary clinical forms, Crohns disease (CD) and ulcerative colitis (UC). Several genetic susceptibility variants have been associated with IBD, such as ATG16L, NOD2, and several human leukocyte antigen (HLA) alleles, nonetheless, the actual disease causes remain unknown. Whereas previous findings have shown elevated responses toward fungal antigens in individuals with IBD, e.g., elevated anti-Saccharomyces cerevisiae antibody (ASCA) levels, an exhaustive mapping of immune responses toward fungal antigens remains incomplete. Thus, we analyzed the fungal mycobiome profiled using internal transcribed spacer 2 (ITS2)-sequencing simultaneously with the T cell repertoire of 637 individuals with IBD from the SPARC IBD cohort, which enabled us to identify 31 T cell clonotypes targeting several prevalent members of the gut mycobiome. Subsequently, we developed a novel phage-immunoprecipitation sequencing (PhIP-Seq) library covering 12,000 potential antigens from the proteome of S. cerevisiae and screened for antibody responses in 100 individuals with CD and 60 healthy controls with known ASCA status, enabling us to identify public and private antibody responses against several S. cerevisiae proteins. In conclusion, we corroborated previous findings showing elevated T cell responses against fungal antigens in individuals with IBD and identified multiple antigenic proteins from the proteome of S. cerevisiae that are targeted by the immune system of individuals with and without CD.

immunology↗