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.
Adult
Aged
Case-Control Studies
Coinfection
/ immunology
DNA, Viral
/ genetics
Female
Flow Cytometry
HIV Infections
/ complications
HIV-1
/ genetics
Herpesvirus 8, Human
/ genetics
Humans
Male
Middle Aged
Real-Time Polymerase Chain Reaction
Sarcoma, Kaposi
/ etiology
Tanzania
Viral Load
Young Adult
Zambia
KSHV
Kaposi
neutralizing antibody
sarcoma
sub-Saharan Africa
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
08 04 2019
08 04 2019
Historique:
received:
02
09
2018
accepted:
09
11
2018
pubmed:
20
11
2018
medline:
9
1
2020
entrez:
20
11
2018
Statut:
ppublish
Résumé
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. KSHV viral DNA (vDNA), total anti-KSHV antibody, KSHV neutralizing antibody (nAb), and cytokines were quantified. 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). Similarities in antibody and cytokine responses between epidemic and endemic KS patients suggest that KSHV drives KS pathogenesis, whereas HIV-1 exacerbates it.
Sections du résumé
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.
Identifiants
pubmed: 30452681
pii: 5191126
doi: 10.1093/infdis/jiy654
pmc: PMC6452303
doi:
Substances chimiques
DNA, Viral
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1318-1328Subventions
Organisme : FIC NIH HHS
ID : D43 TW010354
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA221204
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA075903
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA190155
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM103509
Pays : United States
Informations de copyright
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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