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, Maseno University
Erwan Piriou, SUNY Upstate Medical University
Peter Sumba Odada, Kenya Medical Research Institute
Nancy Fiore, SUNY Upstate Medical University
Jaap M. Middeldorp, VU University Medical Center
Carole Long, National Institutes of Health
Sheetij Dutta, Walter Reed Army Institute of Research
David E. Lanar, Walter Reed Army Institute of Research
Walter G.Z.O. Jura, Maseno University
Collins Ouma, Maseno University
Juliana A. Otieno, Kenya Ministry of Health
Ann M. Moormann, University of Massachusetts Medical School
Rosemary Rochford, SUNY Upstate Medical University

Abstract

BACKGROUND: 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. 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. METHODS: We 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.

RESULTS: Relative 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.

CONCLUSION: Elevated 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.