Evaluation of KIR3DL1/KIR3DS1 allelic polymorphisms in Kenyan children with endemic Burkitt lymphoma

Abstract

Endemic Burkitt lymphoma (eBL) is a fast-growing germinal center B cell lymphoma, affecting 5-10 per 100,000 children annually, in the equatorial belt of Africa. We hypothesize that co-infections with Plasmodium falciparum (Pf) malaria and Epstein-Barr virus (EBV) impair host natural killer (NK) and T cell responses to tumor cells, and thus increase the risk of eBL pathogenesis. NK cell education is partially controlled by killer immunoglobulin-like receptors and variable expression of KIR3DL1 has been associated with other malignancies. Here, we investigated whether KIR3D-mediated mechanisms contribute to eBL, by testing for an association of KIR3DL1/KIR3DS1 genotypes with the disease in 108 eBL patients and 99 healthy Kenyan children. KIR3DL1 allelic typing and EBV loads were assessed by PCR. We inferred previously observed phenotypes from the genotypes. The frequencies of KIR3DL1/KIR3DL1 and KIR3DL1/KIR3DS1 did not differ significantly between cases and controls. Additionally, none of the study participants was homozygous for KIR3DS1 alleles. EBV loads did not differ by the KIR3DL1 genotypes nor were they different between eBL survivors and non-survivors. Our results suggest that eBL pathogenesis may not simply involve variations in KIR3DL1 and KIR3DS1 genotypes. However, considering the complexity of the KIR3DL1 locus, this study could not exclude a role for copy number variation in eBL pathogenesis.

Fig 1. KIR3DL1 genotypes and overall survival (OS) in patients with eBL.

OS of eBL patients encoding KIR3DL1*High, KIR3DL1*Low, and KIR3DL1*Null genotypes were analyzed using the Kaplan-Meier method.

Fig 2. EBV load stratified by KIR3DL1 genotypes and by survival in eBL patients.

Cellular EBV levels were compared for (A) eBL patients (n = 102) and (B) HC (n = 78) after stratification by KIR3DL1 genotypes. In addition, EBV levels were compared between eBL survivors and non-survivors (C). Analyses were performed by Kruskal–Wallis and Mann-Whitney tests. p≤0.05 was considered statistically significant. VL is viral load. Data are median, ns, not significant.