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14th International AIDS ConferenceBarcelona, Spain — July 7-12, 2002 |
Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. TuPeA4427
BACKGROUND: Kaposi's sarcoma (KS) now a frequent tumor in Tanzania develops in a minority of individuals infected with the KS-associated herpes virus KSHV/HHV8 (30-50%), suggesting a complex pathogenesis in KS evolution.
Evidently, HIV-1 strongly promotes KS (AKS), but the mechanisms involved are poorly understood. We have analyzed the presence of HHV8 in biopsies and plasma of AKS and non-AIDS, endemic KS (EKS) patients at various stages of development.METHODS: Cells were studied for expression of HHV8 latent antigen (LANA) and cell markers by combined triple immunostaining and HHV8-DNA in serum by a quantitative, RT-PCR assay.
RESULTS: LANA+ cells varied with stage of AKS and EKS in relation to the number of CD34+ tumor spindle cells (SC). However, a fraction (35-45%) of CD34+ cells at late (nodular) and early (patch, plaque) stages were LANA-negative, suggesting a heterogeneity in this cell population with regard to infectivity. Some (= 5-10%) LANA+ cells in early KS were CD34-negative with an apparent leucocytic morphology. Proliferating Ki67+ cells (6-25%) were seen at all KS stages. These cycling cells were more frequent in AKS than EKS, often LANA-negative, and positive for CD34 or lymphocyte markers. Similar numbers of CD34+ LANA+ cells were seen in comparable KS stages. Serum HHV8 DNA was moderately higher in AKS than EKS and in males than in females. The highest values were seen in an early (patch-plaque), KS-stage male patient, but usually there was no marked variability in serum DNA of comparable KS forms. In positive blood donors (20%), HHV8 serum levels were significantly lower compared to KS patients.
CONCLUSIONS: HHV8 in AKS and EKS biopsies is associated not only with SC, but also with other cells. The majority of CD34+ SC are LANA+ suggesting a selective advantage in viability for infected cells. The presence of significant levels of HHV8 DNA in the serum of both KS and non-KS Tanzanians indicates a high risk for blood viral transmission.
Presenting author: Peter Biberfeld
1Muhimbili University College of Health Sciences, Dept. of Pathology, Immunopathology Lab., Building Z6:03, Karolinska Hospital, S-171 76 Stockholm, Tanzania.
2Immunopathology Lab., Karolinska Institutet, Stockholm, Sweden.
3Swedish Institute for Infectious Disease Control - SMI, Karolinska Institutet, Stockholm, Sweden.
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TuPeA4427
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