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HLA-A alleles and infectious mononucleosis suggest a critical role for cytotoxic T-cell response in EBV-related Hodgkin lymphoma
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2010 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 14, 6400-6405 p.Article in journal (Refereed) Published
Abstract [en]

A proportion of classical Hodgkin lymphoma (HL) is believed to be causally related to infection with the ubiquitous lymphotropic EBV. The determining factors for development of EBV-related HL remain poorly understood, but likely involve immunological control of the viral infection. Accordingly, markers of the HLA class I region have been associated with risk of EBV-related HL. To study the host genetic component of EBV-related HL further, we investigated the lymphoma's association with HLA-A*01 and HLA-A*02 simultaneously in the setting of infectious mononucleosis (IM), a risk factor for EBV-related HL, in a case-series analysis including 278 EBV-related and 656 EBV-unrelated cases of HL. By logistic regression, HLA-A*01 alleles [odds ratio (OR) per allele, 2.15; 95% CI, 1.60-2.88] were associated with increased and HLA-A*02 alleles (OR per allele, 0.70; 95% CI, 0.51-0.97) with decreased risk of EBV-related HL. These allele-specific associations corresponded to nearly 10-fold variation in risk of EBV-related HL between HLA-A*01 and HLA-A*02 homozygotes. History of IM was also associated with risk of EBV-related HL (OR, 3.40; 95% CI, 1.74-6.66). The association between history of IM and EBV-related HL was not seen in the presence of HLA-A*02 because this allele appeared to neutralize the effect of IM on EBV-related HL risk. Our findings suggest that HLA class I-restricted EBV-specific cytotoxic T-cell responses and events in the early immune response to EBV infection in IM play critical roles in the pathogenesis of EBV-related HL.

Place, publisher, year, edition, pages
2010. Vol. 107, no 14, 6400-6405 p.
Keyword [en]
Hodgkin lymphoma
National Category
Hematology Cell and Molecular Biology Clinical Laboratory Medicine Basic Medicine
Research subject
URN: urn:nbn:se:uu:diva-125764DOI: 10.1073/pnas.0915054107ISI: 000276374400050PubMedID: 20308568OAI: oai:DiVA.org:uu-125764DiVA: diva2:320996
Available from: 2010-05-28 Created: 2010-05-28 Last updated: 2015-02-27

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Department of Oncology, Radiology and Clinical ImmunologyDepartment of Immunology, Genetics and Pathology
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Proceedings of the National Academy of Sciences of the United States of America
HematologyCell and Molecular BiologyClinical Laboratory MedicineBasic Medicine

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