Abstract<\/p>\n
Background & Aims<\/p>\n
Elevated antimicrobial antibodies have been reported up to 6 years before diagnosis of Crohn\u2019s disease (CD), but the specific antibody response is unclear. Here, we characterized the antimicrobial antibody responses before CD diagnosis in healthy first-degree relatives (FDRs) of patients with CD.<\/p>\n
Methods<\/p>\n
The CCC-GEM (Crohn\u2019s and Colitis Canada \u2013 Genetic, Environmental, Microbial) Project nested case-control cohort consisted of FDRs who later developed CD (n = 77), matched 1:4 by age, sex, follow-up duration, and geographical location with healthy FDRs (n = 304). Sera at enrollment were probed for antimicrobial reactivity using a microbiota antigen microarray and a flagellin peptide cytometric bead array. Conditional logistic regression was used to assess association with CD onset, and partial Spearman was used to correlate serologic responses with lactulose-to-mannitol ratio (LMR), C-reactive protein (CRP), and fecal calprotectin (FCP). False discovery rate was controlled using the Benjamini-Hochberg method (q < 0.05).<\/p>\n
Results<\/p>\n
Nineteen of 49 IgG antimicrobial antibody responses were significantly associated with the risk of CD; these antibodies were reactive to Lachnospiraceae family, particularly Roseburia-derived flagellins; 5 antibodies positively correlated with FCP, whereas 3 positively correlated with LMR. These IgG-seroreactive flagellins shared significant amino acid sequence homology, characterized by a conserved \u201c\u201dhinge peptide\u201c\u201d within D0\u2013D1 domains of the amino-terminus. The cytometric bead array confirmed that elevated IgG seroreactivity to the hinge peptide is associated with future risk of CD independent of LMR and FCP.<\/p>\n
Conclusions<\/p>\n
Increased antibody response in healthy FDRs towards Lachnospiraceae flagellins is associated with future risk of CD. Importantly, pre-CD subjects shared seroreactivity towards a conserved bacterial flagellin epitope, which may represent an early preclinical biomarker of CD.<\/p>\n","protected":false},"excerpt":{"rendered":"Abstract Background & Aims Elevated antimicrobial antibodies have been reported up to 6 years before diagnosis of Crohn\u2019s…\n","protected":false},"author":2,"featured_media":635624,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[134,111,139,69],"class_list":["post-635623","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-health","tag-new-zealand","tag-newzealand","tag-nz"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/635623","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/comments?post=635623"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/635623\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media\/635624"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media?parent=635623"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/categories?post=635623"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/tags?post=635623"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}