Evidence map›Paper›PMID 26381047›Full record

ArticleTissue antigens2015

The interaction of genetic determinants in the outcome of HCV infection: evidence for discrete immunological pathways.

T J Hydes, B Moesker, J A Traherne, S Ashraf, G J Alexander, B D Dimitrov, C H Woelk, J Trowsdale, S I Khakoo

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Tissue antigens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 11 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

T J HydesClinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
B MoeskerClinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
J A TraherneDepartment of Pathology, University of Cambridge, Cambridge, UK.
S AshrafDepartment of Pathology, University of Cambridge, Cambridge, UK.
G J AlexanderDepartment of Medicine, University of Cambridge, Cambridge, UK.
B D DimitrovClinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
C H WoelkClinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
J TrowsdaleDepartment of Pathology, University of Cambridge, Cambridge, UK.
S I KhakooClinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
University of Southampton · GBUniversity of Cambridge · GB

Funding

Medical Research Council G0901682Medical Research Council G1001738Medical Research Council MR/L016567/1Medical Research Council MR/M019829/1Wellcome Trust 100140Wellcome Trust WT076991MA
6 · The paper itself

Abstract

Diversity within the innate and adaptive immune response to hepatitis C is important in determining spontaneous resolution (SR) and treatment response. The aim of this study was to analyze how these variables interact in combination; furthering our understanding of the mechanisms that drive successful immunological clearance. Multivariate analysis was performed on retrospectively collected data for 357 patients previously genotyped for interferon (IFN)-λ3/4, killer cell immunoglobulin (KIR), human leukocyte antigen (HLA) class I and II and tapasin. High resolution KIR genotyping was performed for individuals with chronic infection and haplotypes determined. Outcomes for SR, IFN response and cirrhosis were examined. Statistical analysis included univariate methods, χ(2) test for trend, multivariate logistic regression, synergy and principal component analysis (PCA). Although KIR2DL3:HLA-C1C1 (P = 0.027), IFN-λ3/4 rs12979860 CC (P = 0.027), tapasin G in individuals with aspartate at residue 114 of HLA-B (TapG:HLA-B(114D) ) (P = 0.007) and HLA-DRB1*04:01 (P = 0.014) were associated with SR with a strong additive influence (χ(2) test for trend P < 0.0001); favorable polymorphisms did not interact synergistically, nor did patients cluster by outcome. In the treatment cohort, IFN-λ3/4 rs12979860 CC was protective in hepatitis C virus (HCV) G1 infection and KIR2DL3:HLA-C1 in HCV G2/3. In common with SR, variables did not interact synergistically. Polymorphisms predictive of viral clearance did not predict disease progression. In summary, different individuals resolve HCV infection using discrete and non-interacting immunological pathways. These pathways are influenced by viral genotype. This work provides novel insights into the complexity of the interaction between host and viral factors in determining the outcome of HCV infection.

Indexed as

Disease ProgressionEpistasis, GeneticGene ExpressionGenetic HeterogeneityGenotypeHepacivirusHepatitis C, ChronicHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHost-Pathogen InteractionsHumansInterferon LambdaInterferonsInterleukinsLiver CirrhosisLogistic ModelsHistocompatibility Antigens Class IHistocompatibility Antigens Class IIIFNL4 protein, humanInterferon Lambdainterferon-lambda, humanInterferonsInterleukinsMembrane Transport ProteinsReceptors, KIRtapasinhepatitis CIFN-λ3/4immunogeneticsinterferonkiller cell immunoglobulin receptorstapasin

Identifiers

PMID26381047
PMCPMC4858811
OpenAlexW1727425826

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.