584063-Bourgonje

119 Haemophilus influenzae, autolysins such as N-acetylmuramoyl-L-alanine amidase of Staphylococcus aureus, and surface proteins of Streptococcus pneumoniae and Streptococcus pyogenes), and several types of virulence factors (including autotransporter proteins of H. influenzae, E. coli and Neisseria meningitides, translocator proteins of E. coli and Pseudomonas aeruginosa and antiphagocytic M proteins of S. pyogenes) occurred less frequent in patients with CD compared to healthy individuals. In addition, antibody responses against wheat allergens were found to be more frequent in patients with CD, including allergens from Triticum aestivum, (common wheat), Secale cereale (rye), Zeamays (maize corn), Aegilops tauschii (wheat), Hordeum vulgare (barley), and Oryza sativa (Asian rice). In contrast, egg allergens (ovomucoid peptides from chickens, Gallus gallus) were decreased in patients with CD compared to healthy individuals. Finally, few antibody responses against human proteins (i.e. autoantigens) were observed to be more frequent in CD, e.g. peptides from the alpha chain of collagen type IV. In contrast to CD, patients with UC did not demonstrate distinct anti-flagellin antibody responses but did exhibit an overrepresentation of antibody responses directed against fibronectin-binding proteins, including fibronectin-binding proteins A and B of S. aureus and fibronectin-binding proteins SfbII and A of S. pyogenes, as well asWxL domain-containing proteins (unknown function), OstA-like domain-containing proteins of Parabacteroides johnsonii (involved in lipopolysaccharide assembly), periplasmic beta-glucosidase BgIX of E. coli (involved in bacterial carbohydrate metabolism) and STN domain-containing proteins (involved in TonB-dependent active uptake of nutrients) of Bacteroides dorei (Table S5, Figure 3B). However, some of these results warrant cautious interpretation, as coagulation-associated antibody-bound peptides may be differentially abundant due to the comparison of serum (which is generally depleted of coagulation proteins) versus plasma (which may still contain coagulation factors). For example, staphylococcal coagulase proteins were markedly underrepresented in UC compared to healthy controls (~5% vs. ~35%, respectively) (Table S5). To address this issue, we also compared antibody responses betweenpatientswithCDandUCusing serumsamples frombothgroups andobserved similar results (Table S8). Patients with UC also demonstrated decreased antibody responses against pneumococcal histidine triad proteins and choline-binding proteins of S. pneumoniae, murein hydrolase activator proteins of E. coli (involved in peptidoglycan turnover, regulating cell wall growth), M proteins of S. pyogenes and several types of bacterial cell wall components (e.g. N-acetylmuramoyl-L-alanine amidase, adhesins of H. influenzae and other surface proteins). In addition, more frequent antibody responses against several viruses (among others, influenza A, hepatitis E, EBV, CMV, and rubella) were observed in patients with UC, concomitantly with decreased antibody responses against respiratory syncytial virus (RSV), rhinoviruses, and Norwalk viruses. Finally, patients with UC demonstrated increased antibody responses against a couple of human autoantigens, including the MAP kinase-activating death domain protein (apoptosis protein), aldolase B (carbohydrate metabolism enzyme), and an ATPase phospholipid transport protein, while they showed decreased antibody responses against the huntingtin protein (involved in axonal transport). The antibody epitope repertoire in IBD

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