Dataset Information

HLA-A2, HLA-B44 and HLA-DR15 are associated with lower risk of BK viremia.

ABSTRACT:

Background

Human leucocyte antigens (HLAs) modulate immunity to polyomavirus BK (BKV). Identification of HLAs that alter the course of infection will facilitate risk stratification, and customization of pre-emptive intervention strategies.

Methods

We performed a retrospective cohort study with 998 kidney transplant patients with BKV infection status confirmed by polymerase chain reaction (PCR). Clinical parameters and donor-recipient matching for specific HLAs were examined in relation to occurrence of viremia. An emphasis was placed on donor-recipient matching rather than the actual frequency of specific HLA-alleles, since a successful immune response requires sharing of HLAs between a virus-infected target cell and the anti-viral effector cell.

Results

Using multivariate statistics, low risk of BK viremia was associated with matching of HLA-A2 [hazard ratio (HR) 0.51, 95% confidence interval (CI) 0.28-0.85], HLA-B44 (HR 0.31, 95% CI 0.076-0.85) and HLA-DR15 (HR 0.35, 95% CI 0.084-0.93) (P < 0.05), whereas high risk of viremia was associated with male gender (HR 2.38, 95% CI 1.46-4.09, P < 0.001).

Conclusions

HLAs that associated with a lower predisposition to the development of BK viremia have been identified. Evaluation of donor-recipient mismatching for these HLAs could potentially be used to (i) fine tune virus screening strategies for BKV in individual patients and (ii) facilitate discovery of major histocompatibility complex (MHC) class I and II binding peptides that can elicit clinically meaningful BKV-specific immunity.

SUBMITTER: Masutani K

PROVIDER: S-EPMC3843344 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Publications

HLA-A2, HLA-B44 and HLA-DR15 are associated with lower risk of BK viremia.

Masutani Kosuke K Ninomiya Toshiharu T Randhawa Parmjeet P

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20130930 12

<h4>Background</h4>Human leucocyte antigens (HLAs) modulate immunity to polyomavirus BK (BKV). Identification of HLAs that alter the course of infection will facilitate risk stratification, and customization of pre-emptive intervention strategies.<h4>Methods</h4>We performed a retrospective cohort study with 998 kidney transplant patients with BKV infection status confirmed by polymerase chain reaction (PCR). Clinical parameters and donor-recipient matching for specific HLAs were examined in rel ...[more]

PMID: 24084328

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Project description:BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease under genetic control. Growing evidences support the genetic predisposition of HLA-DRB1 gene polymorphisms to SLE, yet the results are not often reproducible. The purpose of this study was to assess the association of two polymorphisms of HLA-DRB1 gene (HLA-DR3 and HLA-DR15) with the risk of SLE via a comprehensive meta-analysis.MethodsThis study complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Case-control studies on HLA-DRB1 and SLE were searched from PubMed, Elsevier Science, Springer Link, Medline, and Cochrane Library database as of June 2018. Analysis was based on the random-effects model using STATA software version 14.0.ResultsA total of 23 studies were retained for analysis, including 5261 cases and 9838 controls. Overall analysis revealed that HLA-DR3 and HLA-DR15 polymorphisms were associated with the significant risk of SLE (odds ratio [OR]: 1.60, 95% confidence interval (CI): 1.316-1.934, P = 0.129 and OR: 1.68, 95% CI: 1.334-2.112, P = 0.001, respectively). Subgroup analyses demonstrated that for both HLA-DR3 and HLA-DR15 polymorphisms, ethnicity was a possible source of heterogeneity. Specifically, HLA-DR3 polymorphism was not associated with SLE in White populations (OR: 1.60, 95% CI: 1.320-1.960, P = 0.522) and HLA-DR15 polymorphism in East Asian populations (OR: 1.65, 95% CI: 1.248-2.173, P = 0.001). In addition, source of control was another possible source for both HLA-DR3 and HLA-DR15 polymorphisms, with observable significance for HLA-DR3 in only population-based studies (OR: 1.65, 95% CI: 1.370-1.990, P = 0.244) and for HLA-DR15 in both population-based and hospital-based studies (OR: 1.38, 95% CI: 1.078-1.760, P = 0.123 and OR: 2.08, 95% CI: 1.738-2.490, P = 0.881, respectively).ConclusionsHLA-DRB1 gene may be a SLE-susceptibility gene, and it shows evident ethnic heterogeneity. Further prospective validations across multiple ethnical groups are warranted.

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Dataset Information

HLA-A2, HLA-B44 and HLA-DR15 are associated with lower risk of BK viremia.

Background

Methods

Results

Conclusions

Publications

HLA-A2, HLA-B44 and HLA-DR15 are associated with lower risk of BK viremia.

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