HLA polymorphisms and detection of kaposi sarcoma-associated herpesvirus DNA in saliva and peripheral blood among children and their mothers in the uganda sickle cell anemia KSHV Study

Abstract

Kaposi sarcoma-associated herpesvirus (KSHV, also called Human herpesvirus 8 or HHV8) is a γ-2 herpesvirus that causes Kaposi sarcoma. KSHV seroprevalence rates vary geographically with variable rates recorded in different sub Sahara African countries, suggesting that effects of genetic and/or environmental factors may influence the risk of infection. One study conducted in South Africa, where KSHV seroprevalence is relatively low, found that carriage of human leukocyte antigen (HLA) alleles HLA-A*6801, HLA-A*30, HLA-A*4301, and HLA-DRB1*04 was associated with increased shedding of KSHV DNA in saliva. Confirmation of those results would strengthen the hypothesis that genetic factors may influence KSHV distribution by modulating KSHV shedding in saliva. To explore these associations in another setting, we used high resolution HLA-A, B, and DRB1 typing on residual samples from the Uganda Sickle Cell Anemia KSHV study, conducted in a high KSHV seroprevalence region, to investigate associations between HLA and KSHV shedding in saliva or peripheral blood among 233 children and their mothers. HLA-A and HLA-DRB1 alleles were not associated with KSHV shedding in our study, but our study was small and was not adequately powered to exclude small associations. In exploratory analyses, we found marginal association of KSHV DNA shedding in saliva but not in peripheral blood among children carrying HLA- B*4415 and marginal association of KSHV DNA shedding in peripheral blood but not in saliva among children carrying HLA- B*0801 alleles. The contribution of individual HLA polymorphisms to KSHV shedding is important but it may vary in different populations. Larger population-based studies are needed to estimate the magnitude and direction of association of HLA with KSHV shedding and viral control.

Mutual detection of Kaposi's sarcoma‐associated herpesvirus and Epstein–Barr virus in blood and saliva of Cameroonians with and without Kaposi's sarcoma

“…However, we have previously reported that minority ethnicity was associated with higher KS risk in the same study, possibly suggesting that genetic traits rarer in minorities, ancestrally less exposed to the virus, may play a role in the immune responses to KSHV. We are currently investigating genetic risk factors for KSHV infection and KS in this case–control study; studies conducted in sub‐Saharan Africa reported some evidence of association between HLA polymorphisms and KSHV DNA detection in saliva and/or blood …”

Variation in the Human Leukocyte Antigen system and risk for endemic Burkitt lymphoma in northern Uganda

“…The four most frequent Class II HLA alleles were: DPB1*04 , DRB1*15 , DPB1*01 , DPB1*03 and DPB1*02 ; DQA1*01 , DQA1*05 , DQA1*02 , and DQA1*03 ; HLA‐DQB1*06 , DQB1*05 , DQB1*03 , and DQB1*02 ; and HLA‐DRB1*13 , DRB1*15 , DRB1*01 , and DRB1*03 . The distribution of these alleles in the controls was comparable to the distribution reported in two other populations from Uganda (Guech‐Ongey et al , ) and Kenya (Peterson et al , ).…”

Human leukocyte antigen polymorphisms and Kaposi's sarcoma‐associated herpesvirus infection outcomes: A call for deeper exploration

“…Through presenting a separate analysis of all mothers as well as KSHV‐infected mothers, the authors suggested that the three allele groups—A*68, A*43, and DRB1*04—might increase the likelihood of virus excretion rather than increasing susceptibility to infection with KSHV. However, in a study by Guech‐Ongey et al, the HLA‐A and HLA‐DRB1 alleles were not associated with KSHV shedding in children and their mothers in Uganda. The authors suggest that the contribution of individual HLA polymorphisms to KSHV shedding is important but may vary in different populations.…”