@article{502f678547f24a8b900339f961192411,
title = "Associations between IgG reactivity to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens and Burkitt lymphoma in Ghana and Uganda case-control studies",
abstract = "Background: Endemic Burkitt lymphoma (eBL) is an aggressive childhood B-cell lymphoma linked to Plasmodium falciparum (Pf) malaria in sub-Saharan Africa. We investigated antibody reactivity to several human receptor-binding domains of the Pf erythrocyte membrane protein 1 (PfEMP1) that play a key role in malaria pathogenesis and are targets of acquired immunity to malaria. Methods: Serum/plasma IgG antibody reactivity was measured to 22 Pf antigens, including 18 to PfEMP1 CIDR domains between cases and controls from two populations (149 eBL cases and 150 controls from Ghana and 194 eBL cases and 600 controls from Uganda). Adjusted odds ratios (aORs) for case-control associations were estimated by logistic regression. Findings: There was stronger reactivity to the severe malaria associated CIDRα1 domains than other CIDR domains both in cases and controls. eBL cases reacted to fewer antigens than controls (Ghana: p = 0·001; Uganda: p = 0·03), with statistically significant lower ORs associated with reactivity to 13+ antigens in Ghana (aOR 0·39, 95% CI 0·24–0·63; pheterogeneity = 0·00011) and Uganda (aOR 0·60, 95% CI 0.41–0·88; pheterogeneity = 0·008). eBL was inversely associated with reactivity, coded as quartiles, to group A variant CIDRδ1 (ptrend = 0·035) in Ghana and group B CD36-binding variants CIDRα2·2 (ptrend = 0·006) and CIDRα2·4 (ptrend = 0·033) in Uganda, and positively associated with reactivity to SERA5 in Ghana (ptrend = 0·017) and Uganda (ptrend = 0·007) and group A CIDRα1·5 variant in Uganda only (ptrend = 0·034). Interpretation: eBL cases reacted to fewer antigens than controls using samples from two populations, Ghana and Uganda. Attenuated humoral immunity to Pf EMP1 may contribute to susceptibility to low-grade malaria and eBL risk. Funding: Intramural Research Program, National Cancer Institute and National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services.",
keywords = "Africa, Burkitt lymphoma, Epstein-Barr virus, Non-Hodgkin lymphoma, PfEMP1, Plasmodium falciparum malaria",
author = "Andriy Derkach and Isaac Otim and Pfeiffer, {Ruth M.} and Onabajo, {Olusegun O.} and Legason, {Ismail D.} and Hadijah Nabalende and Ogwang, {Martin D.} and Patrick Kerchan and Talisuna, {Ambrose O.} and Ayers, {Leona W.} and Reynolds, {Steven J.} and Francis Nkrumah and Janet Neequaye and Kishor Bhatia and Theander, {Thor G.} and Ludmila Prokunina-Olsson and Louise Turner and Goedert, {James J.} and Thomas Lavstsen and Mbulaiteye, {Sam M.}",
note = "Funding Information: The study was funded by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI) (Contracts HHSN261201100063C and HHSN261201100007I) and, in part, by the Intramural Research Program, National Institute of Allergy and Infectious Diseases (SJR), National Institutes of Health, US Department of Health and Human Services. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The content of this manuscript is the sole responsibility of the authors. The sponsors had no role in the study design, data collection, analysis, interpretation, writing of the manuscript, or the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Funding Information: The study was funded by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics , National Cancer Institute (NCI) (Contracts HHSN261201100063C and HHSN261201100007I ) and, in part, by the Intramural Research Program , National Institute of Allergy and Infectious Diseases (SJR) , National Institutes of Health , US Department of Health and Human Services . The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The content of this manuscript is the sole responsibility of the authors. The sponsors had no role in the study design, data collection, analysis, interpretation, writing of the manuscript, or the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Publisher Copyright: {\textcopyright} 2018",
year = "2019",
month = jan,
doi = "10.1016/j.ebiom.2018.12.020",
language = "English (US)",
volume = "39",
pages = "358--368",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",
}