HLA Polymorphisms and Epstein-Barr Virus Infection In The Recipient Of Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Lin Ren , Fan Qian , Yu Sijian , Fan Zhiping , Zhang Yu , Huang Fen , Zhou Hongsheng , Xuan Li , Wu Meiqing , Guo Xutao , Dai Min , Sun Jing , Liu Qifa 
Published: October 2019

Abstract

Background
Epstein-Barr virus (EBV) infection/reactivation following allogeneic hematopoietic stem cell transplantation (allo-HSCT) can cause fatal post-transplant lymphoproliferative disorders (PTLD) and other EBV-associated diseases. The development of EBV infection/reactivation and EBV-associated diseases are closely related to the immune function. Human leukocyte antigen (HLA) molecules are responsible for antigen processing and presentation to the immune system. Thus, it is supposed that HLA polymorphisms might be associated with EBV infection/reactivation and EBV-associated diseases. In this study, HLA polymorphisms and EBV infection/reactivation or EBV-associated diseases in the recipients of allo-HSCT were analyzed.

Methods
Three hundred and forty-nine recipients undergoing allo-HSCT were enrolled in this study between July 2008 to June 2013. For recipients and their donors, HLA-A, -B and HLA-DR were analyzed using PCR-sequence specific oligonueleotide probing (PCR-SSOP). The EBV-DNA levels of blood were monitored regularly by quantitative real-time polymerase chain reaction (RQ-PCR).

Results
With a median follow-up of 389 days post-transplantation (range, 7 to 1828 days), 96 cases developed EBV infection/reactivation and 40 developed EBV-associated diseases including 27 EBV-PTLD and 13 other EBV-associated diseases (i.e. 7 fever, 1 pneumonia, 2 encephalitis, 1 hepatitis, 1 encephalitis accompanying pneumonia and 1 enteritis accompanying hepatitis). The 3-year cumulative incidence of EBV infection/reactivation and EBV-associated diseases were 29.1%±2.6% and 13.1%±2.0%, respectively. 43.8% of the recipients with HLA-A11 developed EBV infection/reactivation, compared with 56.5% of those without HLA-A11 (p=0.039). Multivariate analysis showed that HLA-A11 was a protective factor for EBV infection/reactivation (OR 0.497, 95% conﬁdence interval [CI] 0.284-0.869, p=0.014). The recipients who had the donors with HLA-A31 had a higher incidence of EBV-associated diseases than those whose donors did not have HLA-A31 (10.3% vs. 2.9%, p=0.046); more patients carried HLA-B44 suffered EBV-associated diseases than those not carried HLA-B44 (7.7% vs. 1.3%, p=0.035). In multivariate analysis, recipient HLA-B44 were confirmed to be a risk factor for EBV-associated diseases (OR 17.749, 95% conﬁdence interval [CI] 1.946-161.917, p=0.011). The incidence of PTLD in the recipients with HLA-A74 was 7.4%, compared with 0.6% in those without HLA-A74 (p=0.031); the incidences of PTLD in recipients whose donors had and did not have HLA-DR04 were 37.0% and 20.2%, respectively (p=0.042). Multivariate analysis showed that recipient HLA-A74 (OR 11.350, 95%CI: 1.119-115.178, p=0.040) and donor HLA-DR04 (OR 3.227, 95%CI: 1.323-7.873, p=0.010) were risk factors for development of PTLD.

Conclusion
Our data suggest that HLA polymorphisms might affect EBV infection/reactivation and EBV-associated diseases.

Disclosures:
Liu: This work was supported by the National High Technology Research and Development Program of China (863 Program) (No. 2011AA020105), the National Public Health Grand Research Foundation (Grant No. 201202017).: Research Funding; This work was also supported by National Natural Science Foundation of China (Grant No.81000231, No.30971300, No.81270647), the Science and Technology Project of Guangdong Province of China (Grant No.2009A030200007).: Research Funding; This work was also supported by the Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding.