P0295 VIRUS‐SELF CROSSREACTIVITY INDUCING DE NOVO AUTOIMMUNE HEPATITIS EIGHT‐YEARS AFTER LIVER TRANSPLANTATION
Bibliographic record
Abstract
Introduction: The aetiology of autoimmune hepatitis type 2 (AIH-2), characterised by liver-kidney microsomal antibody-type-1 (LKM1) reactive with cytochrome P450IID6 (CYP2D6) is unknown. Hepatitis C virus (HCV) was postulated as trigger of a primary LKM-1 response in a girl following infection at the time of liver transplantation (LT) for end-stage alpha-1 anti-trypsin deficiency-related cirrhosis. Eight years after LT, the girl developed overt de-novo AIH. She had been exposed to Herpes simplex virus-1 (HSV1) and Epstein-Barr virus (EBV) before LT and acquired HCV and cytomegalovirus (CMV) infections after LT. Methods: To characterise the evolving LKM1 autoimmunity and investigate the role of virus/self molecular mimicry in its development, we tested by ELISA 10 serum samples, collected between 1989–2000, and stored at −70 degrees C, for possible cross-reactivity between CYP2D6(252–271), key epitope of LKM1 reactivity, and its HCV, HSV1, CMV, and EBV viral homologues. Results: Before LT only an IgG response to an HSV1 mimic was present. After LT, the newly acquired CYP2D6252–271 response was accompanied by reactivity to E1/HCV, CMV and HSV mimics. Reactivity to EBV mimic became detectable 2 months after LT. When de novo AIH was diagnosed 8 years later, CYP2D6(252–271) reactivity was still present; HCV PCR was negative and cross-reactive antibody responses to E1/HCV and HSV mimics were present. Identical LKM1 reactivity was detected 11 years after LT. Conclusion: Our data suggest that a CYP2D6(252–271) crossreactive lymphocyte population, primed by HSV1, underwent expansion following exposure to mimicking sequences of HCV, CMV and EBV with consequent production of LKM1 and ultimately AIH.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".