Similar Immunological Profiles Between African Endemic and Human Immunodeficiency Virus Type 1–Associated Epidemic Kaposi Sarcoma (KS) Patients Reveal the Primary Role of KS-Associated Herpesvirus in KS Pathogenesis

• Published in: The Journal of infectious diseases 2019-04, Vol.219 (8), p.1318-1328
• Main Authors: Lidenge, Salum J., Tso, For Yue, Ngalamika, Owen, Ngowi, John R., Mortazavi, Yasaman, Kwon, Eun Hee, Shea, Danielle M., Minhas, Veenu, Mwaiselage, Julius, Wood, Charles, West, John T.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies; Case-Control Studies; Coinfection - immunology; Coinfection - virology; Cytokines; DNA, Viral - genetics; Epidemics; Female; Flow Cytometry; Herpesvirus 8, Human - genetics; Herpesvirus 8, Human - immunology; HIV; HIV Infections - complications; HIV Infections - immunology; HIV Infections - virology; HIV-1 - genetics; HIV-1 - immunology; Human immunodeficiency virus; Humans; Immune response; Interleukin 10; Interleukin 5; Kaposis sarcoma; Leukocytes (mononuclear); Major and Brief Reports; Male; Middle Aged; Pathogenesis; PATHOGENESIS AND HOST RESPONSE; Peripheral blood mononuclear cells; Polymerase chain reaction; Real-Time Polymerase Chain Reaction; Sarcoma; Sarcoma, Kaposi - etiology; Sarcoma, Kaposi - virology; Tanzania; Tumors; Viral Load; Young Adult; Zambia
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiy654

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. Lack of immune response studies in African endemic Kaposi sarcoma (KS) makes the pathogenetic role of HIV-1 unclear. Similarities in antibody and cytokine responses between epidemic and endemic KS patients suggest that KSHV drives KS pathogenesis, whereas HIV-1 exacerbates it.