Evaluation of the antibody response to the EBV proteome in EBV‐associated classical Hodgkin lymphoma. Issue 3 (14th November 2019)

• Record Type: Journal Article
• Authors: Liu, Zhiwei; Jarrett, Ruth F.; Hjalgrim, Henrik; Proietti, Carla; Chang, Ellen T.; Smedby, Karin E.; Yu, Kelly J.; Lake, Annette; Troy, Sally; McAulay, Karen A.; Pfeiffer, Ruth M.; Adami, Hans‐Olov; Glimelius, Bengt; Melbye, Mads; Hildesheim, Allan; Doolan, Denise L.; Coghill, Anna E.
• Is Part Of: International journal of cancer. Volume 147:Issue 3(2020)
• Page Start: 608
• Page End: 618
• Publication Date: 2019-11-14
• Subjects: EBV and cancer -- Hodgkin lymphoma -- EBV antibody patterns; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.32741
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : The humoral immune response to Epstein–Barr virus (EBV) in classical Hodgkin lymphoma (cHL) stratified by EBV tumor status is unclear. We examined IgG and IgA antibody responses against 202 protein sequences representing 86 EBV proteins using a microarray and sera from 139 EBV‐positive cHL cases, 70 EBV‐negative cHL cases and 141 population‐based controls frequency matched to EBV‐positive cHL cases on sex and age by area (UK, Denmark and Sweden). We leveraged existing data on the proportion of circulating B‐cells infected by EBV and levels of serum CCL17, a chemokine secreted by cHL tumor cells, from a subset of the cHL cases in the UK. Total IgG but not IgA response level was significantly different between EBV‐positive cHL cases and controls. The distinct serological response included significant elevations in 16 IgG antibodies and 2 IgA antibodies, with odds ratioshighest vs . lowest tertile > 3 observed for the following EBV proteins: LMP1 (oncogene), BcLF1 (VCAp160, two variants) and BBLF1 (two variants). Our cHL IgG signature correlated with the proportion of circulating EBV‐infected B‐cells, but not serum CCL17 levels. We observed no differences in the anti‐EBV antibody profile between EBV‐negative cHL cases and controls. BdRF1(VCAp40)‐IgG and BZLF1(Zta)‐IgG were identified as the serological markers best able to distinguish EBV‐positive from EBV‐negative cHL tumors. Our results support the hypothesis that differences in the EBV antibody profile are specific to patients with EBV‐positive cHL and are not universally observed as part of a systematically dysregulated immune response present in all cHL cases. Abstract : What's new? Previous studies of Epstein–Barr virus in classical Hodgkin lymphoma (cHL) have been limited to only a few antibodies or protein complexes. In this study, the authors used a new protein microarray technology to measure both IgG and IgA antibody responses against far more EBV proteins. They found systemic differences in the EBV antibody profile in cHL cases, which are both specific to EBV‐positive tumors, and include immune aberrations that reflect exposure to multiple stages of the viral life cycle. Evidence of increased, systemic exposure to EBV lytic‐cycle activity supports a role for ongoing viral activity in tumor pathogenesis.