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Record W4396709309 · doi:10.1101/2024.05.04.24306873

Elevated polyreactive immunoglobulin G in immune mediated liver injuries with the need for immunosuppressive therapy

2024· preprint· en· W4396709309 on OpenAlexaff
Theresa Kirchner, George Ν. Dalekos, Kalliopi Zachou, Mercedes Robles‐Díaz, Raúl J. Andrade, Marcial Sebode, Ansgar W. Lohse, Maciej K. Janik, Piotr Milkiewicz, Mirjam Kolev, Nasser Semmo, Tony Bruns, Tom J.G. Gevers, Benedetta Terziroli Beretta‐Piccoli, Heiner Wedemeyer, Elmar Jaeckel, Richard Taubert

Bibliographic record

VenuemedRxiv · 2024
Typepreprint
Languageen
FieldMedicine
TopicLiver Diseases and Immunity
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsImmune systemAntibodyImmunologyImmunoglobulin GImmunoglobulin MMedicine

Abstract

fetched live from OpenAlex

Abstract Background and aim The distinction of drug-induced liver injury (DILI), drug-induced autoimmune-like hepatitis (DI-ALH) and autoimmune hepatitis (AIH) can be challenging due to overlapping clinical characteristics. Recently, polyreactive immunoglobulin G (pIgG) was identified as a novel biomarker with a higher accuracy for the diagnose of AIH than conventional autoantibodies. This retrospective multicenter study aimed to evaluate the diagnostic accuracy of pIgG to distinguish between AIH, DI-ALH and DILI and thus identify patients in need of immunosuppression. Methods Samples from 116 patients (AIH=81, DI-ALH=12, DILI=23) were recruited and compared to a control group (non-AIH-non-DILI-LD= 596) from existing biorepositories. Results No patient in the DILI-group but 98% in the AIH-and 92% in the DI-ALH-group received immunosuppressive treatment. pIgG levels were significantly higher in the AIH-group (1.9 normalized arbitrary units (nAU) compared to DILI (1.1 nAU, p<0.001) and non-AIH-non-DILI-LD (1.0 nAU, p<0.001). Median pIgG concentrations of the DI-ALH-group (1.7 nAU) were between AIH (p=.634) and DILI (p=.052). Patients that needed immunosuppressive therapy for remission induction had significantly higher pIgG concentrations compared to those with spontaneous recovery of liver injury (1.8 nAU vs. 1.1 nAU, p<.001). The overall accuracy of pIgG >1.27nAU to distinguish AIH from DILI (74%) and liver injuries with and without the need for immunosuppression (74%) was similar to that of ANA (71/74%) and SMA (74/70%) at cut-offs of ≥1/40. Conclusion Polyreactive IgG can be used to predict AIH in comparison to DILI and indicate the need for immunosuppressive therapy in the work-up of immune mediated or drug-induced liver injuries.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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.

Opus teacher head0.018
GPT teacher head0.271
Teacher spread0.254 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2024
Admission routes1
Has abstractyes

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