Cytokine signatures of transformed B cells with distinct Epstein-Barr virus latencies as a potential diagnostic tool for B cell lymphoma.

Immunocompromised individuals, including those infected with human immunodeficiency virus (HIV), are at increased risk of Epstein-Barr virus (EBV)-associated aggressive B cell malignancies such as Burkitt's lymphoma (BL) or diffuse large B cell lymphoma (DLBCL). Differential diagnosis of these lymphomas requires histopathological, immunohistochemical and cytogenetic assessments. Rapid, less invasive approaches to the diagnosis of EBV-associated B cell lymphomas are needed. Here, high-throughput cytokine profiling of BL cell lines and EBV-transformed B lymphoblastoid cell lines (B-LCL), representing DLBCL, was carried out. By monitoring the production of 42 different cytokines, unique cytokine signatures were identified for BL and B-LCL/DLBCL. The BL cells produced interleukin (IL)-10, 10 kDa interferon gamma-induced protein (IP-10)/CXCL10, macrophage-derived chemokine (MDC)/CCL22, macrophage inflammatory protein (MIP)-1α/CCL3 and MIP-1β/CCL4. In addition to these five cytokines, the cytokine signature of B-LCL/DLBCL cells included IL-8/CXCL8, IL-13, platelet-derived growth factor (PDGF)-AA, and regulated upon activation, normal T cell expressed and secreted (RANTES)/CCL5. Epstein-Barr virus latency was responsible for the increased production of IL-10, MDC/CCL22 and MIP-1α/CCL3 in BL cells, suggesting that EBV-mediated BL-genesis involves these three cytokines. These results suggest that high-throughput cytokine profiling might be a valuable tool for the differential diagnosis and might deepen our understanding of the pathogenesis of EBV-associated B cell malignancies.