Clinical associations and potential novel antigenic targets of autoantibodies directed against rods and rings in chronic hepatitis C infection
Bibliographic record
Abstract
BACKGROUND: Chronic hepatitis C virus (HCV) infection is frequently associated with extrahepatic autoimmune disorders while interferon (IFN) and ribavirin treatment may exacerbate these conditions. Autoantibodies from HCV patients identify a novel indirect immunofluorescence (IIF) pattern on HEp-2 cells characterized by cytoplasmic rods and rings (RR). Our objectives were to determine the prevalence and clinical associations of RR autoantibodies in HCV patients, and identify related novel autoantibody targets. METHODS: Sera from 315 patients with HCV (301 treatment naive, 14 treated with interferon and/or ribavirin) were analyzed for the presence of RR antibodies by IIF on commercially available HEp-2 cell substrates. Antibodies to inosine monophosphate dehydrogenase 2 (IMPDH2) and cytidine triphosphate synthase 1 (CTPS1) were detected by addressable laser bead assay and other potential targets were identified by immunoscreening a protein microarray. Clinical and demographic data including HCV genotype, mode of infection, prior antiviral therapy, and histological findings were compared between RR antibody positive (RR+) and negative (RR-) patients. RESULTS: The median age of the HCV cohort was 51 years, 61% were male, and 76% were infected with HCV genotype 1 (G1). Four percent (n=14) had been treated with IFN-based therapy (IFN monotherapy, n=3; IFN/ribavirin, n=11); all had a sustained virologic response. In total, 15 patients (5% of the cohort) were RR+. RR+ and RR- patients had similar demographic and clinical characteristics including age, sex, mode of HCV infection, prevalence of the G1 HCV genotype, and moderate to severe fibrosis. Nevertheless, RR+ patients were significantly more likely than RR- cases to have been treated with IFN-based therapy (33% vs. 3%; adjusted odds ratio 20.5 [95% confidence interval 5.1-83.2]; P<0.0005). Only 1/10 RR positive sera had detectable antibodies to IMPHD2 and none had antibodies to CTPS1. Potentially important autoantibody targets identified on protein arrays included Myc-associated zinc finger protein (MAZI) and ankyrin repeat motif. CONCLUSION: The majority of HCV patients with RR autoantibodies previously received IFN/ribavirin antiviral therapy. Further studies are necessary to determine the genesis of intracellular RR and elucidate the clinically relevant autoantigens as well as the clinical and prognostic significance of their cognate autoantibodies.
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 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 | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".