116 (IQR: 721–1,362, full range: 179– 2722). Overall antibody epitope diversity was similar for patients with CD and UC (median with IQR: 1,015 [721;1,365] and 1,015 [721;1,341], respectively, P = 0.325, Figure 2D). More than 100,000 antibody-bound peptides were positive in at least one individual, whereas only a few peptides were shared among all patients (Figure 2E). These observations, which indicate the existence of both individual-specific and population-wide antibody responses, are in line with recent studies that performed PhIP-Seq analysis in population-based cohorts.12,22 In fact, just 2,368 different antigen peptides were present in 5–95% of individual patients with IBD (Figure 2F), with 83% of peptides shared between both IBD subtypes and the remaining 17% specific to either CD or UC. Figure 2 | Overall characterization of serum antibody epitope repertoires in patients with IBD. (A–C) Principal component analysis (PCA) plots demonstrating the first two principal components (PCs) describing data variation. (A) IBD diagnosis could partially explain PC1, but was not associated to PC2. (B) Antibody diversity, i.e. the number of significantly enriched antigen peptides per patient, was significantly associated to both PCs. (C) A k-means clustering algorithm (k = 2) successfully separated two distinct clusters, and these appeared to be based on the enrichment of antigen peptides from herpes virus proteins, particularly cytomegalovirus. (D) Antigen peptide diversities among patients with CD and UC show comparable distributions, with a median of 1,015 peptides per patient. Lines indicate kernel density estimates of the CD- and UC-specific distributions. (E) Prevalence of antigen epitope repertoires amongst all patients, showing that tens of thousands of antigen peptides were found in only a single patient, while only few peptides were shared among the full study cohort. (F) Venn diagram showing the prevalence of significantly enriched antigen peptides amongst patients with CD (n = 256) and UC (n = 207) (diagnoses of IBD-U excluded here), indicating that a large proportion of peptides are shared among patients with CD and UC. Abbreviations: CD, Crohn’s disease; PC, principal component; Q1, first quartile (25th percentile); Q3, third quartile (75th percentile); UC, ulcerative colitis. Chapter 4
RkJQdWJsaXNoZXIy MjY0ODMw