Development of serological tools for diagnosis of human herpesvirus 8 infection and their application to estimate antibody prevalence in English blood and organ donor populations
Anna Godi1, Yara Hajarha1,2, Stephen Dicks1,2, Keerthana Jegatheesan1,2, Samreen Ijaz1, Ines Ushiro-Lumb1,2.
1Blood Borne Virus Unit, Virus Reference Department, UK Health Security Agency, London, United Kingdom; 2Organ and Tissue Donation and Transplantation , National Health Service Blood and Transplant , London, United Kingdom
Introduction: Human Herpesvirus 8 (HHV-8), also known as Kaposi sarcoma-associated herpes virus, is aetiologically associated with all forms of Kaposi's Sarcoma (KS), including transplant-related, as well as rare neoplastic conditions such as primary effusion lymphomas and multicentric Castleman disease. Solid organ transplant recipients have a much higher risk of KS compared to the general population and the role of serological screening in this setting has been long debated; there is currently no standard method of screening for HHV-8 infection and serology has been largely used for sero-epidemiological purposes. The latent nature of the virus makes determination of HHV-8 infection status complex and investigations may lead to inaccuracies.
Methods: To fulfil the critical gaps in the diagnosis of asymptomatic virus infection, a combination of serological tools for the detection of antibody to both HHV-8 lytic and latent antigens have been developed and compared with the commercial lytic antigen-based immunofluorescence assay (IFA, Scimedx Corp), which is commonly used in Europe for the detection of antibodies to HHV-8. The developed assays include an in-house latent IFA assay that utilises latently infected PEL cells as well as two Double Antigen Binding Assays (DABAs) which utilise major HHV-8 antigens; ORF73 and K8.1 e(latent and lytic proteins, respectively).
Results: Initial data gained from the testing of samples from identified patients with ongoing HHV-8 disease indicate a good concordance between both latent and lytic antibody assays. Studies are underway to determine the performance of these assays for the identification of asymptomatic infection and are being applied to establish the prevalence of HHV-8 antibodies in donor populations.
Conclusion: HHV-8 has a complex serological profile and the availability of tools based on a range of formats which target multiple proteins will better inform on seroprevalence rates both at a population level and within specific at-risk groups.