Pediatric HIV+ Kaposi sarcoma exhibits clinical, virological, and molecular features different from the adult disease
Carolina Caro-Vegas, … , Dirk P. Dittmer, Nader Kim El-Mallawany
Carolina Caro-Vegas, … , Dirk P. Dittmer, Nader Kim El-Mallawany
Published November 22, 2023
Citation Information: JCI Insight. 2023;8(22):e167854. https://doi.org/10.1172/jci.insight.167854.
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Clinical Research and Public Health AIDS/HIV Oncology

Pediatric HIV+ Kaposi sarcoma exhibits clinical, virological, and molecular features different from the adult disease

Abstract

BACKGROUND Kaposi sarcoma (KS) is among the most common childhood cancers in Eastern and Central Africa. Pediatric KS has a distinctive clinical presentation compared with adult KS, which includes a tendency for primary lymph node involvement, a considerable proportion of patients lacking cutaneous lesions, and a potential for fulminant disease. The molecular mechanisms or correlates for these disease features are unknown.METHODS This was a cross-sectional study. All cases were confirmed by IHC for KS-associated herpesvirus (KSHV) LANA protein. Baseline blood samples were profiled for HIV and KSHV genome copy numbers by qPCR and secreted cytokines by ELISA. Biopsies were characterized for viral and human transcription, and KSHV genomes were determined when possible.RESULTS Seventy participants with pediatric KS were enrolled between June 2013 and August 2019 in Malawi and compared with adult patients with KS. They exhibited high KSHV genome copy numbers and IL-6/IL-10 levels. Four biopsies (16%) had a viral transcription pattern consistent with lytic viral replication.CONCLUSION The unique features of pediatric KS may contribute to the specific clinical manifestations and may direct future treatment options.FUNDING US National Institutes of Health U54-CA-254569, PO1-CA019014, U54-CA254564, RO1-CA23958.

Authors

Carolina Caro-Vegas, Alice Peng, Angelica Juarez, Allison Silverstein, William Kamiyango, Jimmy Villiera, Casey L. McAtee, Rizine Mzikamanda, Tamiwe Tomoka, Erin C. Peckham-Gregory, Razia Moorad, Carrie L. Kovarik, Liane R. Campbell, Parth S. Mehta, Peter N. Kazembe, Carl E. Allen, Michael E. Scheurer, Nmazuo W. Ozuah, Dirk P. Dittmer, Nader Kim El-Mallawany

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Figure 2

Systemic viral and cytokine levels in pediatric KS.

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Systemic viral and cytokine levels in pediatric KS. HIV viral load versu...
HIV viral load versus CD4 count from (A) pediatric KS (n = 21) versus (B) adult KS (n = 207). (C) KSHV viral load in pediatric KS compared with adult KS (n = 207). The dotted line represents the limit of detection at 1,000 copies/mL. (D) IL-6 and IL-10 levels on patient plasma with pediatric KS, measured by ELISA. Red and blue represent elevated levels of IL-6 and IL-10, respectively (above 100 pg/mL). Each data point represents the mean of n = 3 independent measurements, and the median was calculated for the entire group (unpaired 2-tailed t test; **P < 0.01). (E) KSHV, (F) IL-6, and (G) IL-10 levels in plasma from pediatric patients with KS at different time points. Only patients with 3 or more visits were included. Yellow and blue represent patients with elevated levels of KSHV and IL-10. Green represents a patient with elevated levels of IL-6, and red represents a patient with moderate levels of KSHV, IL-6, and IL-10. Patients marked in gray had no significant levels of any marker. Each data point represents the mean of n = 3 independent measurements.