Association between HLA class II alleles and protection from or susceptibility to chronic hepatitis C

Zavaglia, Claudio; Martinetti, Miryam; Silini, Enrico Maria; Bottelli, R.; Daielli, C.; Asti, M.; Airoldi, Aldo; Salvaneschi, L.; Mondelli, Mario U.; Idéo, G.

doi:10.1016/s0168-8278(98)80195-5

Cited by 88 publications

(80 citation statements)

References 24 publications

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“…In terms of HLA‐class I, HLA‐B*08 has been linked to viral persistence in the Irish HCV and an US cohort, but could not be replicated in an East German population 33, 34, 35. HLA‐DQB1*0301 was found to be protective in largely Caucasian cohorts in France, the UK and Italy, but only in black populations in the United States, showing that geographical location, and hence the infecting HCV virion may be a determinant of response rather than ethnicity alone 18, 36, 37, 38. Finally, the protective influence of tapasin occurs in European Caucasians but not US Caucasians 9.…”

Section: Discussionmentioning

confidence: 96%

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

et al. 2015

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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, χ2 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‐B114D) (P = 0.007) and HLA‐DRB1*04:01 (P = 0.014) were associated with SR with a strong additive influence (χ2 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.

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Section: Discussionmentioning

confidence: 96%

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

et al. 2015

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“…15 Differences in the immunogenetic background of HCV-infected individuals might, in part, account for the observed variation in viral-specific immunity and courses of disease. 16 In this regard, binding of HCV peptides to HLA molecules is a critical step for the initiation of an antigen-specific immune response. Previous work from Virahep-C has indicated that baseline HCV-specific immunity is associated with SVR; 17 patients with higher levels of CD4 þ T-cell responses are more likely to develop SVR than patients with lower pretreatment levels.…”

Section: Discussionmentioning

confidence: 99%

Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection

Rhodes

Erlich

et al. 2008

Genes Immun

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The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in antigen presentation and regulation of CD8 þ and CD4 þ T cells. Response to therapies in hepatitis C virus (HCV) infection is highly variable (30-80%) and lower response rates have been reported among African Americans (AA; B30%) compared to Caucasian Americans (CA; B50%) infected with genotype-1 viruses. We evaluated whether MHC gene variants were associated with response to therapy and racial differences in AA and CA sustained virologic response (SVR) rates. We genotyped alleles at 8 MHC loci: 3 class I (A, B and C) and 5 class II (DRB1, DQA1, DQB1, DPA1 and DPB1) loci in 373 individuals (179 AA and 194 CA) with genotype-1 HCV infections, who were treated with peginterferon-a-2a and ribavirin. We observed carriage of A*02 (RR ¼ 1.33(1.08-1.64); P ¼ 0.008), B *58 (RR ¼ 1.84(1.24-2.73); P ¼ 0.002) and DPB1*1701 (RR ¼ 1.57(1.09-2.26); P ¼ 0.015) to be associated with SVR after adjustment for other predictors of response. In analysis of AA and CA subgroups separately, we observed potential, though not statistically significant, differences in these MHC associations. Variation in the immunogenetic background of HCV-infected individuals might account for some observed variation in viral-specific immunity and courses of disease. In this regard, future studies examining broader patient populations are warranted.

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“…22 Possession of HLA-DR11 has been linked to rapid progression of the AIDS virus in a Caucasian French population and also to protection from chronic Hepatitis C in an Italian population. 23,24 Current knowledge suggests that the level of production and efficiency of IFNg is a central determinant for the outcomes of C. burnetii host interactions. In turn it is reasonable to suppose that polymorphisms in the IFNg gene and that of its receptor will modulate the process.…”

Section: Discussionmentioning

confidence: 99%

Variation in immune response genes and chronic Q fever. Concepts: preliminary test with post-Q fever fatigue syndrome

Helbig¹,

Heatley

Harris³

et al. 2003

Genes Immun

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Acute primary Q fever is followed by various chronic sequelae. These include subacute Q fever endocarditis, granulomatous reactions in various organs or a prolonged debilitating post-infection fatigue syndrome (QFS). The causative organism, Coxiella burnetii, persists after an initial infection. The differing chronic outcomes may reflect variations within cytokine and accessory immune control genes which affect regulation of the level of persistence. As a preliminary test of the concept we have genotyped QFS patients and controls for gene variants spanning 15 genes and also examined HLA-B and DR frequencies. QFS patients exhibited a significantly increased frequency of HLA-DR-11 compared with controls and also significant differences in allelic variant frequencies within the NRAMP, and IFNg genes. These results indicate a possible genetic role in the expression of overt chronic Q fever. Further studies will be undertaken to increase sample sizes, to survey other forms of chronic Q fever and to examine Q fever patients who have recovered without sequelae.

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Association between HLA class II alleles and protection from or susceptibility to chronic hepatitis C

Cited by 88 publications

References 24 publications

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

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

Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection

Variation in immune response genes and chronic Q fever. Concepts: preliminary test with post-Q fever fatigue syndrome

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