Serum IgA to Epstein-Barr virus early antigen-diffuse identifies Hodgkin's lymphoma

Hodgkin's lymphoma is associated with immune dysregulation. Immune impairment often results in aberrant immune responses and lytic reactivation of ubiquitous Herpesviruses, such as Epstein-Barr virus (EBV) in mucosal tissues. Accordingly, the specificity of IgA to EBV early lytic antigens, which are important for reactivation, was evaluated to determine Hodgkin's lymphoma-specific sero-reactive patterns. Sera from 42 patients with Hodgkin's lymphoma were compared to sera from 17 patients with infectious mononucleosis (IM), another EBV-related condition that often presents in a similar manner; and to sera from 15 healthy EBV-seropositive subjects. Flow cytometry analysis demonstrated that like IM sera, most Hodgkin's lymphoma sera contained IgA that labeled cells expressing EBV early lytic antigens whereas healthy EBV-seropositive sera did not. Further evaluation to distinguish Hodgkin's lymphoma from IM showed that IgA in most Hodgkin's lymphoma, irrespective of the presence of EBV in primary tumors, detected only modified forms of EBV lytic Early Antigen-Diffuse (EA-D) while IM sera detected the un-modified form as well, further supporting the presence of immune dysregulation in Hodgkin's lymphoma patients. This IgA pattern distinguished Hodgkin's lymphoma from IM sera with a sensitivity of 92.9%, specificity 100%, positive predictive value 100%, and negative predictive value 85%. Our findings lay the groundwork for additional scientific and clinical investigation, particularly into the potential for developing Hodgkin's lymphoma-associated diagnostic and prognostic biomarkers.