Associations between IgG reactivity to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens and Burkitt lymphoma in Ghana and Uganda case-control studiesResearch in context
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 ro...
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| Format: | Article |
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Elsevier
2019-01-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396418305978 |
| _version_ | 1818338900626636800 |
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| author | Andriy Derkach Isaac Otim Ruth M. Pfeiffer Olusegun O. Onabajo Ismail D. Legason Hadijah Nabalende Martin D. Ogwang Patrick Kerchan Ambrose O. Talisuna Leona W. Ayers Steven J. Reynolds Francis Nkrumah Janet Neequaye Kishor Bhatia Thor G. Theander Ludmila Prokunina-Olsson Louise Turner James J. Goedert Thomas Lavstsen Sam M. Mbulaiteye |
| author_facet | Andriy Derkach Isaac Otim Ruth M. Pfeiffer Olusegun O. Onabajo Ismail D. Legason Hadijah Nabalende Martin D. Ogwang Patrick Kerchan Ambrose O. Talisuna Leona W. Ayers Steven J. Reynolds Francis Nkrumah Janet Neequaye Kishor Bhatia Thor G. Theander Ludmila Prokunina-Olsson Louise Turner James J. Goedert Thomas Lavstsen Sam M. Mbulaiteye |
| author_sort | Andriy Derkach |
| collection | DOAJ |
| description | 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: Non-Hodgkin lymphoma, Plasmodium falciparum malaria, PfEMP1, Epstein-Barr virus, Burkitt lymphoma, Africa |
| first_indexed | 2024-12-13T15:18:28Z |
| format | Article |
| id | doaj.art-86c01784983c474b9b73e9a198f63f6c |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-13T15:18:28Z |
| publishDate | 2019-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-86c01784983c474b9b73e9a198f63f6c2022-12-21T23:40:38ZengElsevierEBioMedicine2352-39642019-01-0139358368Associations between IgG reactivity to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens and Burkitt lymphoma in Ghana and Uganda case-control studiesResearch in contextAndriy Derkach0Isaac Otim1Ruth M. Pfeiffer2Olusegun O. Onabajo3Ismail D. Legason4Hadijah Nabalende5Martin D. Ogwang6Patrick Kerchan7Ambrose O. Talisuna8Leona W. Ayers9Steven J. Reynolds10Francis Nkrumah11Janet Neequaye12Kishor Bhatia13Thor G. Theander14Ludmila Prokunina-Olsson15Louise Turner16James J. Goedert17Thomas Lavstsen18Sam M. Mbulaiteye19Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USAEMBLEM Study, African Field Epidemiology Network, Kampala, UgandaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USALaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USAEMBLEM Study, African Field Epidemiology Network, Kampala, UgandaEMBLEM Study, African Field Epidemiology Network, Kampala, UgandaEMBLEM Study, St. Mary's Hospital, Lacor, Gulu, UgandaEMBLEM Study, Kuluva Hospital, Arua, UgandaWorld Health Organization, Regional Office for Africa, Brazzaville, CongoDepartment of Pathology, The Ohio State University, Columbus, OH, USADivision of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USANoguchi Memorial Institute, Accra, GhanaDepartment of Child Health, Korle Bu University Teaching Hospital in Accra, GhanaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USACentre for Medical Parasitology, Department of International Health, Immunology & Microbiology, University of Copenhagen and Department of Infectious Diseases, Rigs Hospitalet, Copenhagen, DenmarkLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USACentre for Medical Parasitology, Department of International Health, Immunology & Microbiology, University of Copenhagen and Department of Infectious Diseases, Rigs Hospitalet, Copenhagen, DenmarkDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USACentre for Medical Parasitology, Department of International Health, Immunology & Microbiology, University of Copenhagen and Department of Infectious Diseases, Rigs Hospitalet, Copenhagen, DenmarkDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Corresponding author at: 9609 Medical Center Dr, Rm. 6E118 MSC 9706, Bethesda, MD 20892-9704, USA.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: Non-Hodgkin lymphoma, Plasmodium falciparum malaria, PfEMP1, Epstein-Barr virus, Burkitt lymphoma, Africahttp://www.sciencedirect.com/science/article/pii/S2352396418305978 |
| spellingShingle | Andriy Derkach Isaac Otim Ruth M. Pfeiffer Olusegun O. Onabajo Ismail D. Legason Hadijah Nabalende Martin D. Ogwang Patrick Kerchan Ambrose O. Talisuna Leona W. Ayers Steven J. Reynolds Francis Nkrumah Janet Neequaye Kishor Bhatia Thor G. Theander Ludmila Prokunina-Olsson Louise Turner James J. Goedert Thomas Lavstsen Sam M. Mbulaiteye Associations between IgG reactivity to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens and Burkitt lymphoma in Ghana and Uganda case-control studiesResearch in context EBioMedicine |
| title | Associations between IgG reactivity to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens and Burkitt lymphoma in Ghana and Uganda case-control studiesResearch in context |
| title_full | Associations between IgG reactivity to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens and Burkitt lymphoma in Ghana and Uganda case-control studiesResearch in context |
| title_fullStr | Associations between IgG reactivity to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens and Burkitt lymphoma in Ghana and Uganda case-control studiesResearch in context |
| title_full_unstemmed | Associations between IgG reactivity to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens and Burkitt lymphoma in Ghana and Uganda case-control studiesResearch in context |
| title_short | Associations between IgG reactivity to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens and Burkitt lymphoma in Ghana and Uganda case-control studiesResearch in context |
| title_sort | associations between igg reactivity to plasmodium falciparum erythrocyte membrane protein 1 pfemp1 antigens and burkitt lymphoma in ghana and uganda case control studiesresearch in context |
| url | http://www.sciencedirect.com/science/article/pii/S2352396418305978 |
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