HLA expression and HLA type associations in relation to EBV status in Hispanic Hodgkin lymphoma patients

PLoS One. 2017 Mar 23;12(3):e0174457. doi: 10.1371/journal.pone.0174457. eCollection 2017.

Abstract

A proportion of classical Hodgkin lymphomas harbor the Epstein Barr virus (EBV). We previously demonstrated that associations between Human Leukocyte Antigen (HLA) alleles and susceptibility to EBV+ classical Hodgkin lymphoma differ between European and Chinese populations. Data on Hispanic populations is missing. Here we examined the association between HLA type, tumor cell HLA expression and other characteristics in Hispanic Hodgkin lymphoma patients. Hispanic Hodgkin lymphoma patients diagnosed at the Los Angeles County-University of Southern California Medical Center from 2000-2012 were included (n = 65). Formalin-fixed paraffin-embedded tumor tissue was analyzed for EBV by in situ hybridization and for HLA class I and class II expression by immunohistochemistry. HLA typing was performed by HLA-A specific quantitative PCR of genomic DNA from tissue. Thirty patients (46%) had EBV+ tumors. Expression of HLA class I (p = 0.0006) was significantly associated with EBV+ tumor status in Hispanic patients, similar to Europeans and Chinese. A positive association between HLA class II expression and EBV+ tumor status, as present in large studies in Europeans, was not found (p = 0.06). The prevalences of the specific European HLA-A*01 risk and European HLA-A*02 protective types were not significantly associated with EBV+ tumors among these Hispanic patients, however numbers were too low to draw firm conclusions. The HLA-A*02:07 allele, that is associated with EBV+ Hodgkin lymphoma in Chinese, was absent. In conclusion, the association between EBV positivity in tumor cells and HLA class I expression appears to be consistent across different populations. Larger studies in Hispanics are needed to evaluate HLA allele susceptibility associations.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Child
  • Child, Preschool
  • Epstein-Barr Virus Infections / genetics
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Infections / virology
  • Female
  • Gene Frequency
  • HLA Antigens / genetics*
  • Herpesvirus 4, Human / isolation & purification*
  • Hodgkin Disease / genetics
  • Hodgkin Disease / immunology*
  • Hodgkin Disease / virology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Young Adult

Substances

  • HLA Antigens

Grants and funding

The project described was supported in part by award numbers P30CA014089 and 1R01CA206019-01 from the National Cancer Institute (www.cancer.gov) to Wendy Cozen. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The project was also supported by a grant from the Dutch Cancer Society (KWF RUG 2014-6698;www.kwf.nl/english) to Anke van den Berg and Arjan Diepstra. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.