Trends in Kaposi's sarcoma-associated Herpesvirus antibodies prior to the development of HIV-associated Kaposi's sarcoma: a nested case-control study.

Katie Wakeham,Denise Whitby,Billy N Mayanja,Wendell Miley,W Thomas Johnston,Alison M Elliott,Emily L Webb,Robert Newton,Angela Nalwoga

doi:10.1002/ijc.29329

Abstract

HIV-associated Kaposi's sarcoma (KS) is a public health challenge in sub-Saharan Africa since both the causative agent, Kaposi's sarcoma associated-herpesvirus (KSHV), and the major risk factor, HIV, are prevalent. In a nested case-control study within a long-standing clinical cohort in rural Uganda, we used stored sera to examine the evolution of antibody titres against the KSHV antigens K8.1 and latency-associated nuclear antigen (LANA) among 30 HIV-infected subjects who subsequently developed HIV-related KS (cases) and among 108 matched HIV/KSHV coinfected controls who did not develop KS. Throughout the 6 years prior to diagnosis, antibody titres to K8.1 and LANA were significantly higher among cases than controls (p < 0.0001), and titres increased prior to diagnosis in the cases. K8.1 titres differed more between KS cases and controls, compared to LANA titres. These differences in titre between cases and controls suggest a role for lytic viral replication in the pathogenesis of HIV-related KS in this setting.

Highlights

Trends in Kaposi’s sarcoma-associated Herpesvirus antibodies prior to the development of HIV-associated Kaposi’s sarcoma: A nested case-control study
The study has shown that individuals who develop HIV-associated Kaposi’s sarcoma (KS) have higher K8.1 and latency-associated nuclear antigen (LANA) antibody titres compared to those who do not, and that this is evident up to 6 years prior to KS diagnosis
The results presented here are in accord with studies conducted among cohorts based in the West; antibody titres against Kaposi’s sarcoma associated-herpesvirus (KSHV) antigens are higher among cases and increase prior to tumor diagnosis.[5,6,8,16,29]

Summary

Introduction

Trends in Kaposi’s sarcoma-associated Herpesvirus antibodies prior to the development of HIV-associated Kaposi’s sarcoma: A nested case-control study. Kaposi’s sarcoma (KS) is currently the most commonly reported cancer in Uganda and in other parts of sub-Saharan Africa[1] where both the underlying cause, Kaposi’s sarcoma associated-herpesvirus (KSHV), and a key risk factor, HIV, are prevalent. K8.1, respectively.[2] In case-control studies from South Africa and Uganda, high antibody titres against KSHV have been observed in patients with KS compared to controls.[3,4] Longitudinal studies in North America and Northern Europe report that elevated antibody titres against KSHV antigens LANA and/or K8.1 are present prior to the onset of clinically evident KS.[5,6,7,8] there are no longitudinal studies describing the evolution of antibodies against KSHV prior to the development of KS from the African continent, despite both virus and tumor being relatively frequent there. The introduction of antiretroviral therapy (ART) in the US and Europe has been associated with a substantial decrease in both the incidence and

Methods

Results

Conclusion