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

Kosuke Masutani, Toshiharu Ninomiya, Parmjeet Randhawa

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 virusinfected 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 BKVspecific immunity.

Original languageEnglish
Pages (from-to)3119-3126
Number of pages8
JournalNephrology Dialysis Transplantation
Volume28
Issue number12
DOIs
Publication statusPublished - Dec 1 2013

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Viremia
HLA Antigens
varespladib methyl
Confidence Intervals
Tissue Donors
Immunity
BK Virus
Infection
Major Histocompatibility Complex
Cohort Studies
Retrospective Studies
Alleles
Viruses
Transplants
Kidney
Polymerase Chain Reaction
Peptides

All Science Journal Classification (ASJC) codes

  • Nephrology
  • Transplantation

Cite this

HLA-A2, HLA-B44 and HLA-DR15 are associated with lower risk of BK viremia. / Masutani, Kosuke; Ninomiya, Toshiharu; Randhawa, Parmjeet.

In: Nephrology Dialysis Transplantation, Vol. 28, No. 12, 01.12.2013, p. 3119-3126.

Research output: Contribution to journalArticle

Masutani, Kosuke ; Ninomiya, Toshiharu ; Randhawa, Parmjeet. / HLA-A2, HLA-B44 and HLA-DR15 are associated with lower risk of BK viremia. In: Nephrology Dialysis Transplantation. 2013 ; Vol. 28, No. 12. pp. 3119-3126.
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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 virusinfected 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 BKVspecific immunity.",
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N2 - 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 virusinfected 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 BKVspecific immunity.

AB - 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 virusinfected 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 BKVspecific immunity.

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