Variation in the Human Leukocyte Antigen system and risk for endemic Burkitt lymphoma in northern Uganda

Kirimunda, Samuel; Verboom, Murielle; Otim, Isaac; Ssennono, Mark; Legason, Ismail D.; Nabalende, Hadijah; Ogwang, Martin D.; Kerchan, Patrick; Kinyera, Tobias; Mwebaza, Ivan; Joloba, Moses; Ayers, Leona W.; Reynolds, Steven J.; Bhatia, Kishor; Onabajo, Olusegun O.; Hallensleben, Michael; Biggar, Robert J.; Prokunina‐Olsson, Ludmila; Goedert, James J.; Blasczyk, Rainer; Mbulaiteye, Sam M.

doi:10.1111/bjh.16398

Cited by 4 publications

(2 citation statements)

References 48 publications

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“…The HLA typing of blood cells and of the RPE cell line was performed in the Institute of Transfusion Medicine, Hannover Medical School, using high resolution, targeted next-generation sequencing (NGS) of the HLA region as previously described ( 76 ).…”

Section: Methodsmentioning

confidence: 99%

Human Cytomegalovirus pUL11, a CD45 Ligand, Disrupts CD4 T Cell Control of Viral Spread in Epithelial Cells

Osanyinlusi

Zischke

Jacobs

et al. 2022

mBio

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Section: Methodsmentioning

confidence: 99%

Human Cytomegalovirus pUL11, a CD45 Ligand, Disrupts CD4 T Cell Control of Viral Spread in Epithelial Cells

Osanyinlusi

Zischke

Jacobs

et al. 2022

mBio

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“…HLA also demonstrates significant links with other EBV-associated cancers, including HL, BL ( 92 ), and PTLD ( 93 ). For example, the HLA-A01 allele increases the risk of EBV-positive HL, whereas HLA-A02 has a protective effect ( 58 ).…”

Section: Ebv-specific T Cell Immunity In Ebv-related Cancersmentioning

confidence: 99%

EBV-induced T-cell responses in EBV-specific and nonspecific cancers

Zhang,

2023

Front. Immunol.

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Epstein-Barr virus (EBV) is a ubiquitous human tumor virus associated with various malignancies, including B-lymphoma, NK and T-lymphoma, and epithelial carcinoma. It infects B lymphocytes and epithelial cells within the oropharynx and establishes persistent infection in memory B cells. With a balanced virus-host interaction, most individuals carry EBV asymptomatically because of the lifelong surveillance by T cell immunity against EBV. A stable anti-EBV T cell repertoire is maintained in memory at high frequency in the blood throughout persistent EBV infection. Patients with impaired T cell immunity are more likely to develop life-threatening lymphoproliferative disorders, highlighting the critical role of T cells in achieving the EBV-host balance. Recent studies reveal that the EBV protein, LMP1, triggers robust T-cell responses against multiple tumor-associated antigens (TAAs) in B cells. Additionally, EBV-specific T cells have been identified in EBV-unrelated cancers, raising questions about their role in antitumor immunity. Herein, we summarize T-cell responses in EBV-related cancers, considering latency patterns, host immune status, and factors like human leukocyte antigen (HLA) susceptibility, which may affect immune outcomes. We discuss EBV-induced TAA-specific T cell responses and explore the potential roles of EBV-specific T cell subsets in tumor microenvironments. We also describe T-cell immunotherapy strategies that harness EBV antigens, ranging from EBV-specific T cells to T cell receptor-engineered T cells. Lastly, we discuss the involvement of γδ T-cells in EBV infection and associated diseases, aiming to elucidate the comprehensive interplay between EBV and T-cell immunity.

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Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with elevated risk of childhood Burkitt lymphoma

Liu,

Luo,

Kirimunda

et al. 2024

Commun Biol

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Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10−6), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10−8), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10−6). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control.

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Variation in the Human Leukocyte Antigen system and risk for endemic Burkitt lymphoma in northern Uganda

Cited by 4 publications

References 48 publications

Human Cytomegalovirus pUL11, a CD45 Ligand, Disrupts CD4 T Cell Control of Viral Spread in Epithelial Cells

Human Cytomegalovirus pUL11, a CD45 Ligand, Disrupts CD4 T Cell Control of Viral Spread in Epithelial Cells

EBV-induced T-cell responses in EBV-specific and nonspecific cancers

Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with elevated risk of childhood Burkitt lymphoma

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