A159 SERUM IGG RESPONSE TO THE D0-D1 HINGE PEPTIDE OF COMMENSAL FLAGELLIN PREDICTS THE FUTURE ONSET OF CROHN’S DISEASE IN HEALTHY FIRST-DEGREE RELATIVES
Bibliographic record
Abstract
Abstract Background Elevated antimicrobial antibody levels have been reported up to 6 years before diagnosis of Crohn’s disease (CD), but the specific antibody response is poorly defined. Aims Here, we characterized the nature of the antimicrobial antibody responses before the diagnosis of CD in healthy first-degree relatives (FDR) of CD patients. Methods The CCC-GEM 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 FDRs who remained healthy (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 the serologic responses with gut permeability (fractional urinary excretion of lactulose-to-mannitol ratio (LMR)) and fecal calprotectin (FCP). Results 19 (out 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 (q<0.02); 5 antibodies positively correlated with FCP (q<0.046), whereas 3 antibodies positively correlated with LMR (q<0.049). These IgG-seroreactive flagellins shared significant amino acid sequence homology, characterized by a conserved “hinge peptide” within D0-D1 domains of the amino-terminus. Elevated IgG seroreactivity to this hinge peptide (determined by cytometric bead array) was associated with multi-flagellin reactivity and future risk of CD. Conclusions Increased antibody response in healthy asymptomatic FDRs towards Lachnospiraceae flagellins is associated with future risk of CD, and markers of gut inflammation and altered intestinal permeability. Importantly, pre-CD participants shared seroreactivity towards a conserved bacterial flagellin epitope, suggesting a possible role in the early immunopathogenesis of CD. Funding Agencies CCC, CIHRThe Leona M. and Harry B. Helmsley Charitable Trust
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".