Association of killer cell immunoglobulin-like receptors with endemic Burkitt lymphoma in Kenyan children
Abstract Endemic Burkitt lymphoma (eBL) is an aggressive pediatric B cell lymphoma, common in Equatorial Africa. Co-infections with Epstein-Barr virus (EBV) and Plasmodium falciparum, coupled with c-myc translocation are involved in eBL etiology. Infection-induced immune evasion mechanisms to avoid...
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2021-05-01
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Online Access: | https://doi.org/10.1038/s41598-021-90596-7 |
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doaj-c8bb22471a264e9294c72f6d71cd58d12021-06-06T11:35:08ZengNature Publishing GroupScientific Reports2045-23222021-05-011111910.1038/s41598-021-90596-7Association of killer cell immunoglobulin-like receptors with endemic Burkitt lymphoma in Kenyan childrenBeatrice M. Muriuki0Catherine S. Forconi1Peter O. Oluoch2Jeffrey A. Bailey3Anita Ghansah4Ann M. Moormann5John M. Ong’echa6West African Center for Cell Biology of Infectious Pathogens, College of Basic and Applied Sciences, University of GhanaDivision of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical SchoolCenter for Global Health Research, Kenya Medical Research InstituteDepartment of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown UniversityNoguchi Memorial Institute for Medical Research, College of Health Sciences, University of GhanaDivision of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical SchoolCenter for Global Health Research, Kenya Medical Research InstituteAbstract Endemic Burkitt lymphoma (eBL) is an aggressive pediatric B cell lymphoma, common in Equatorial Africa. Co-infections with Epstein-Barr virus (EBV) and Plasmodium falciparum, coupled with c-myc translocation are involved in eBL etiology. Infection-induced immune evasion mechanisms to avoid T cell cytotoxicity may increase the role of Natural killer (NK) cells in anti-tumor immunosurveillance. Killer immunoglobulin-like receptor (KIR) genes on NK cells exhibit genotypic and allelic variations and are associated with susceptibility to diseases and malignancies. However, their role in eBL pathogenesis remains undefined. This retrospective study genotyped sixteen KIR genes and compared their frequencies in eBL patients (n = 104) and healthy geographically-matched children (n = 104) using sequence-specific primers polymerase chain reaction (SSP-PCR) technique. The relationship between KIR polymorphisms with EBV loads and eBL pathogenesis was investigated. Possession of ≥ 4 activating KIRs predisposed individuals to eBL (OR = 3.340; 95% CI 1.530–7.825; p = 0.004). High EBV levels were observed in Bx haplogroup (p = 0.016) and AB genotypes (p = 0.042) relative to AA haplogroup and AA genotype respectively, in eBL patients but not in healthy controls. Our results suggest that KIR-mediated NK cell stimulation could mute EBV control, contributing to eBL pathogenesis.https://doi.org/10.1038/s41598-021-90596-7 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Beatrice M. Muriuki Catherine S. Forconi Peter O. Oluoch Jeffrey A. Bailey Anita Ghansah Ann M. Moormann John M. Ong’echa |
spellingShingle |
Beatrice M. Muriuki Catherine S. Forconi Peter O. Oluoch Jeffrey A. Bailey Anita Ghansah Ann M. Moormann John M. Ong’echa Association of killer cell immunoglobulin-like receptors with endemic Burkitt lymphoma in Kenyan children Scientific Reports |
author_facet |
Beatrice M. Muriuki Catherine S. Forconi Peter O. Oluoch Jeffrey A. Bailey Anita Ghansah Ann M. Moormann John M. Ong’echa |
author_sort |
Beatrice M. Muriuki |
title |
Association of killer cell immunoglobulin-like receptors with endemic Burkitt lymphoma in Kenyan children |
title_short |
Association of killer cell immunoglobulin-like receptors with endemic Burkitt lymphoma in Kenyan children |
title_full |
Association of killer cell immunoglobulin-like receptors with endemic Burkitt lymphoma in Kenyan children |
title_fullStr |
Association of killer cell immunoglobulin-like receptors with endemic Burkitt lymphoma in Kenyan children |
title_full_unstemmed |
Association of killer cell immunoglobulin-like receptors with endemic Burkitt lymphoma in Kenyan children |
title_sort |
association of killer cell immunoglobulin-like receptors with endemic burkitt lymphoma in kenyan children |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-05-01 |
description |
Abstract Endemic Burkitt lymphoma (eBL) is an aggressive pediatric B cell lymphoma, common in Equatorial Africa. Co-infections with Epstein-Barr virus (EBV) and Plasmodium falciparum, coupled with c-myc translocation are involved in eBL etiology. Infection-induced immune evasion mechanisms to avoid T cell cytotoxicity may increase the role of Natural killer (NK) cells in anti-tumor immunosurveillance. Killer immunoglobulin-like receptor (KIR) genes on NK cells exhibit genotypic and allelic variations and are associated with susceptibility to diseases and malignancies. However, their role in eBL pathogenesis remains undefined. This retrospective study genotyped sixteen KIR genes and compared their frequencies in eBL patients (n = 104) and healthy geographically-matched children (n = 104) using sequence-specific primers polymerase chain reaction (SSP-PCR) technique. The relationship between KIR polymorphisms with EBV loads and eBL pathogenesis was investigated. Possession of ≥ 4 activating KIRs predisposed individuals to eBL (OR = 3.340; 95% CI 1.530–7.825; p = 0.004). High EBV levels were observed in Bx haplogroup (p = 0.016) and AB genotypes (p = 0.042) relative to AA haplogroup and AA genotype respectively, in eBL patients but not in healthy controls. Our results suggest that KIR-mediated NK cell stimulation could mute EBV control, contributing to eBL pathogenesis. |
url |
https://doi.org/10.1038/s41598-021-90596-7 |
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