Salum J Lidenge1,2,3,4, For Yue Tso1,2, Owen Ngalamika5, John R Ngowi3, Yasaman Mortazavi1,2, Eun Hee Kwon1, Danielle M Shea1, Veenu Minhas6, Julius Mwaiselage3,4, Charles Wood1,2, John T West1. 1. Nebraska Center for Virology, University of Nebraska-Lincoln, Dar es Salaam, Tanzania. 2. School of Biological Sciences, University of Nebraska-Lincoln, Dar es Salaam, Tanzania. 3. Ocean Road Cancer Institute, Dar es Salaam, Tanzania. 4. Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. 5. Dermatology and Venereology Section, University Teaching Hospitals, University of Zambia School of Medicine, Lusaka. 6. Department of Epidemiology, College of Public Health, University of Nebraska Medical Center, Omaha.
Abstract
BACKGROUND: Kaposi sarcoma (KS)-associated herpesvirus (KSHV) is etiologically linked to all KS forms, but mechanisms underlying KS development are unclear. The incidence of KS in human immunodeficiency virus type 1-infected (HIV-1+) individuals implicates immune dysregulation; however, the lack of characterization of KSHV immune responses in endemic KS makes the role of HIV-1 unclear. The study objective was to investigate the HIV-1 and KSHV roles in viral nucleic acid detection, antibody responses, and cytokine responses in polymerase chain reaction-confirmed epidemic KS and endemic KS patients and non-cancer controls from sub-Saharan Africa. METHODS: KSHV viral DNA (vDNA), total anti-KSHV antibody, KSHV neutralizing antibody (nAb), and cytokines were quantified. RESULTS: KSHV vDNA was detectable in tumors but variably in plasma and peripheral blood mononuclear cells. Consistent with elevated antibody-associated cytokines (interleukin [IL] 6, IL-5, and IL-10), nAb titers were higher in epidemic KS and endemic KS patients than in controls (P < .05). Despite HIV-1 coinfection in epidemic KS, nAb titers were similar between epidemic KS and endemic KS patients (P = 0.3). CONCLUSIONS: Similarities in antibody and cytokine responses between epidemic and endemic KS patients suggest that KSHV drives KS pathogenesis, whereas HIV-1 exacerbates it.
BACKGROUND:Kaposi sarcoma (KS)-associated herpesvirus (KSHV) is etiologically linked to all KS forms, but mechanisms underlying KS development are unclear. The incidence of KS in human immunodeficiency virus type 1-infected (HIV-1+) individuals implicates immune dysregulation; however, the lack of characterization of KSHV immune responses in endemic KS makes the role of HIV-1 unclear. The study objective was to investigate the HIV-1 and KSHV roles in viral nucleic acid detection, antibody responses, and cytokine responses in polymerase chain reaction-confirmed epidemic KS and endemic KS patients and non-cancer controls from sub-Saharan Africa. METHODS:KSHV viral DNA (vDNA), total anti-KSHV antibody, KSHV neutralizing antibody (nAb), and cytokines were quantified. RESULTS:KSHV vDNA was detectable in tumors but variably in plasma and peripheral blood mononuclear cells. Consistent with elevated antibody-associated cytokines (interleukin [IL] 6, IL-5, and IL-10), nAb titers were higher in epidemic KS and endemic KS patients than in controls (P < .05). Despite HIV-1 coinfection in epidemic KS, nAb titers were similar between epidemic KS and endemic KS patients (P = 0.3). CONCLUSIONS: Similarities in antibody and cytokine responses between epidemic and endemic KS patients suggest that KSHV drives KS pathogenesis, whereas HIV-1 exacerbates it.
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