Soluble Markers of B-Cell Stimulation During Asymptomatic and Symptomatic Malaria Parasitemia in Children in Uganda

Abstract

Abstract 28 Background: In vitro, Burkitt lymphoma (BL) cell lines express high levels of several cytokines, including CCL3/MIP-1 alpha, CXCL10/IP-10, and IL-10, among others. These cytokines may promote lymphoma development through B- cell hyperstimulation. To understand the influence of malaria infection on cytokine expression in vivo and the potential role in BL development, we sought to characterize the expression of specific cytokines during malaria among children from a region where malaria and BL are endemic. Methods: We studied children participating in a prospective malaria cohort in Uganda. Plasma cytokines were assessed in each child at 3 time points representing 3 disease states: no malaria, asymptomatic malaria, and symptomatic malaria. We assessed both equality of cytokine distribution at the 3 time points using Kruskal-Wallis test and the factors associated with cytokine expression using generalized estimating equations. Results: Among the 41 children, median age was 5.0 (0.8-10.3) years when normal, 5.9 (0.8-10.6) years during asymptomatic malaria, and 5.7 (0.5-10.8) years during symptomatic malaria; 39% (16/41) participants were female. There was a significant increase for IL-10 (p<0.001), IL-6 (p=0.04) and IP-10 (p=0.002) during malaria parasitemia compared to no malaria. In the adjusted models, for every one log increase in the parasite density, the odds of high IL10 expression increased by 80% (OR=1.8, 95% CI: 1.3-2.6, P=<0.001), the odds of high IL6 by 30% (OR=1.3, 95% CI: 1.0-1.7, p=0.04), and the odds of high TNFα by 40% (OR=1.4, 95% CI: 1.1-1.8, p=0.01). Younger children (0-4.9 years) had 400% (OR=5, 95% CI=1.7-25, p=0.001) increase in the odds of high IL10 expression compared to older counterparts (5-11 years). Conclusion: Infection with malaria parasites is associated with an immunological response characterized by elevated B-cell stimulatory cytokines including: IL10, IL6, TNFalpha and IP10. These cytokines may mediate B-cell stimulation and related oncogenic DNA changes that lead to BL. Results of EBV viremia are forthcoming. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: Innocent Mutyaba No relationship to disclose Pauline Byakika-Kibwika No relationship to disclose Warren Phipps No relationship to disclose Corey Casper Leadership: Temptime Corporation Consulting or Advisory Role: Janssen Pharmaceuticals Research Funding: Janssen Pharmaceuticals Travel, Accommodations, Expenses: GlaxoSmithKline, Temptime Corporation Moses Kamya No relationship to disclose