Elevated anti-Zta IgG levels and EBV viral load are associated with site of tumor presentation in endemic Burkitt's lymphoma patients: a case control study

Amolo S Asito,Erwan Piriou,Ann M Moormann,Jaap M Middeldorp,Nancy Fiore,Sheetij Dutta,Rosemary Rochford,David E Lanar,Peter Sumba Odada,Collins Ouma,Juliana A Otieno,Walter Gzo Jura,Carole Long

doi:10.1186/1750-9378-5-13

Abstract

BackgroundEndemic Burkitt's lymphoma (BL) is an extranodal tumor appearing predominantly in the jaw in younger children while abdominal tumors predominate with increasing age. Previous studies have identified elevated levels of antibodies to Plasmodium falciparum schizont extracts and Epstein-Barr virus (EBV) viral capsid antigens (VCA) in endemic BL relative to malaria exposed controls. However, these studies have neither determined if there were any differences based on the site of clinical presentation of the tumor nor examined a broader panel of EBV and P. falciparum antigens.MethodsWe used a suspension bead Luminex assay to measure the IgG levels against EBV antigens, VCA, EAd, EBNA-1 and Zta as well as P. falciparum MSP-1, LSA-1, and AMA-1 antigens in children with BL (n = 32) and in population-based age-and sex-matched controls (n = 25) from a malaria endemic region in Western Kenya with high incidence of BL. EBV viral load in plasma was determined by quantitative PCR.ResultsRelative to healthy controls, BL patients had significantly increased anti-Zta (p = 0.0017) and VCA IgG levels (p < 0.0001) and plasma EBV viral loads (p < 0.0001). In contrast, comparable IgG levels to all P. falciparum antigens tested were observed in BL patients compared to controls. Interestingly, when we grouped BL patients into those presenting with abdominal tumors or with jaw tumors, we observed significantly higher levels of anti-Zta IgG levels (p < 0.0065) and plasma EBV viral loads (p < 0.033) in patients with abdominal tumors compared to patients with jaw tumors.ConclusionElevated antibodies to Zta and elevated plasma EBV viral load could be relevant biomarkers for BL and could also be used to confirm BL presenting in the abdominal region.

Highlights

Endemic Burkitt’s lymphoma (BL) is an extranodal tumor appearing predominantly in the jaw in younger children while abdominal tumors predominate with increasing age
Study participant demographic characteristics Children with endemic BL were recruited at admission to Nyanza Provincial General Hospital (NPGH), the major referral hospital for cancer treatment in Nyanza province, Kenya
When the BL patients were stratified into clinical groups based on site of tumor presentation, children presenting with jaw tumors were younger [mean age, 5.6 years (IQR, 3.8-6.5)] than those presenting with abdominal tumors [mean age, 9.2 years (IQR, 6.3-11.00)] (p = 0.0018)

Summary

Introduction

Endemic Burkitt’s lymphoma (BL) is an extranodal tumor appearing predominantly in the jaw in younger children while abdominal tumors predominate with increasing age. Previous studies have identified elevated levels of antibodies to Plasmodium falciparum schizont extracts and Epstein-Barr virus (EBV) viral capsid antigens (VCA) in endemic BL relative to malaria exposed controls. These studies have neither determined if there were any differences based on the site of clinical presentation of the tumor nor examined a broader panel of EBV and P. falciparum antigens. Endemic Burkitt’s lymphoma (BL) is the most common pediatric cancer in areas that experience stable Plasmodium falciparum transmission, and both Epstein-Barr virus infection (EBV) and holoendemic P. falciparum are thought to be etiologically linked to this B cell neoplasm [1,2,3,4]. Despite the fact that endemic BL has several distinct clinical pictures, most studies have looked at endemic BL as a single clinical entity

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