Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma.

Francesco Vitale, Georgina Mbisa, Paola Cordiali-Fei, James J. Goedert, Elizabeth E. Brown, Carmela Lauria, Christine Gamache, Anthony J. Alberg, Diego Serraino, Denise Whitby, Angelo Messina, Vickie Marshall

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Abstract

BACKGROUND. Classic Kaposi sarcoma (CKS) is an inflammatory-mediated neoplasm that develops in the presence of KS-associated herpesvirus (KSHV) and immune perturbation. In the current study, the authors compared CKS cases with age-matched and sex-matched KSHV-seropositive controls without human immunodeficiency virus-1 infection and markers of viral control, blood counts, CD4-positive and CD8-positive lymphocytes, and serum β-2-microglobulin and neopterin levels. METHODS. Viral loads were detected using real-time amplification of the KSHV-K6 and EBV-pol genes, anti-K8.1 (lytic) titers were detected by enzyme-linked immunoadsorbent assay, and antilatent nuclear antigen (LANA) titers were detected using immunofluorescence. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using logistic regression adjusted for sex, age, and study site. RESULTS. Peripheral blood mononuclear cells (PBMC) KSHV DNA detection (P ≤ .0001) and high KSHV lytic (>1:1745; P ≤ .0001) and latent (>1:102,400; P = .03) antibody titers were found to be positively associated with CKS risk. Antibody titers were higher in cases with lesions compared with cases without lesions (P ≤ .05). The detection of Epstein-Barr virus (EBV) DNA in PBMCs was not found to be associated with CKS (P = .95). Independent of PBMC KSHV DNA, CKS risk was found to be positively associated with reduced hematocrit (<37.4%; P = .03), hemoglobin (<12g/dL; P = .04), and lymphocytes (<1000 cells/μL; P = .004), including CD4-positive (+) cells (<457 cells/μL; P = .07) and CD8+ cells (<213cells/μL; P = .04), and with increased monocytes (≥638 cells/μL; P = .009). Nonsignificant elevations of β-2-microglobulin and neopterin were observed among cases regardless of disease burden (P ≥ .08). In a multivariate model, the CKS risk was found to be associated with PBMC KSHV DNA (OR of 2.7; 95% CI, 1.4-5.3), a high KSHV lytic antibody titer (OR of 3.7; 95% CI, 1.9-7.4), and low lymphocytes, particularly among those patients age <70 years (OR of 8.0; 95% CI, 2.7-23.7). CONCLUSIONS. The findings of the current study appear to corroborate the specificity of KSHV and highlight the hematologic and immunologic correlates involved in the pathogenesis of CKS.
Original languageEnglish
Pages (from-to)2282-2290
JournalCancer
Volume107
Publication statusPublished - 2006

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Kaposi's Sarcoma
Herpesviridae
Immunologic Factors
Odds Ratio
Confidence Intervals
Neopterin
Blood Cells
DNA
Human Herpesvirus 4
Antibodies
CD8-Positive T-Lymphocytes
Lymphocytes
pol Genes
Nuclear Antigens
Immunosorbents
Virus Diseases
CD4 Lymphocyte Count
Viral Load
Hematocrit
Fluorescent Antibody Technique

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Vitale, F., Mbisa, G., Cordiali-Fei, P., Goedert, J. J., Brown, E. E., Lauria, C., ... Marshall, V. (2006). Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma. Cancer, 107, 2282-2290.

Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma. / Vitale, Francesco; Mbisa, Georgina; Cordiali-Fei, Paola; Goedert, James J.; Brown, Elizabeth E.; Lauria, Carmela; Gamache, Christine; Alberg, Anthony J.; Serraino, Diego; Whitby, Denise; Messina, Angelo; Marshall, Vickie.

In: Cancer, Vol. 107, 2006, p. 2282-2290.

Research output: Contribution to journalArticle

Vitale, F, Mbisa, G, Cordiali-Fei, P, Goedert, JJ, Brown, EE, Lauria, C, Gamache, C, Alberg, AJ, Serraino, D, Whitby, D, Messina, A & Marshall, V 2006, 'Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma.', Cancer, vol. 107, pp. 2282-2290.
Vitale F, Mbisa G, Cordiali-Fei P, Goedert JJ, Brown EE, Lauria C et al. Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma. Cancer. 2006;107:2282-2290.
Vitale, Francesco ; Mbisa, Georgina ; Cordiali-Fei, Paola ; Goedert, James J. ; Brown, Elizabeth E. ; Lauria, Carmela ; Gamache, Christine ; Alberg, Anthony J. ; Serraino, Diego ; Whitby, Denise ; Messina, Angelo ; Marshall, Vickie. / Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma. In: Cancer. 2006 ; Vol. 107. pp. 2282-2290.
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title = "Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma.",
abstract = "BACKGROUND. Classic Kaposi sarcoma (CKS) is an inflammatory-mediated neoplasm that develops in the presence of KS-associated herpesvirus (KSHV) and immune perturbation. In the current study, the authors compared CKS cases with age-matched and sex-matched KSHV-seropositive controls without human immunodeficiency virus-1 infection and markers of viral control, blood counts, CD4-positive and CD8-positive lymphocytes, and serum β-2-microglobulin and neopterin levels. METHODS. Viral loads were detected using real-time amplification of the KSHV-K6 and EBV-pol genes, anti-K8.1 (lytic) titers were detected by enzyme-linked immunoadsorbent assay, and antilatent nuclear antigen (LANA) titers were detected using immunofluorescence. Odds ratios (OR) and 95{\%} confidence intervals (95{\%} CI) were calculated using logistic regression adjusted for sex, age, and study site. RESULTS. Peripheral blood mononuclear cells (PBMC) KSHV DNA detection (P ≤ .0001) and high KSHV lytic (>1:1745; P ≤ .0001) and latent (>1:102,400; P = .03) antibody titers were found to be positively associated with CKS risk. Antibody titers were higher in cases with lesions compared with cases without lesions (P ≤ .05). The detection of Epstein-Barr virus (EBV) DNA in PBMCs was not found to be associated with CKS (P = .95). Independent of PBMC KSHV DNA, CKS risk was found to be positively associated with reduced hematocrit (<37.4{\%}; P = .03), hemoglobin (<12g/dL; P = .04), and lymphocytes (<1000 cells/μL; P = .004), including CD4-positive (+) cells (<457 cells/μL; P = .07) and CD8+ cells (<213cells/μL; P = .04), and with increased monocytes (≥638 cells/μL; P = .009). Nonsignificant elevations of β-2-microglobulin and neopterin were observed among cases regardless of disease burden (P ≥ .08). In a multivariate model, the CKS risk was found to be associated with PBMC KSHV DNA (OR of 2.7; 95{\%} CI, 1.4-5.3), a high KSHV lytic antibody titer (OR of 3.7; 95{\%} CI, 1.9-7.4), and low lymphocytes, particularly among those patients age <70 years (OR of 8.0; 95{\%} CI, 2.7-23.7). CONCLUSIONS. The findings of the current study appear to corroborate the specificity of KSHV and highlight the hematologic and immunologic correlates involved in the pathogenesis of CKS.",
author = "Francesco Vitale and Georgina Mbisa and Paola Cordiali-Fei and Goedert, {James J.} and Brown, {Elizabeth E.} and Carmela Lauria and Christine Gamache and Alberg, {Anthony J.} and Diego Serraino and Denise Whitby and Angelo Messina and Vickie Marshall",
year = "2006",
language = "English",
volume = "107",
pages = "2282--2290",
journal = "Cancer",
issn = "0008-543X",
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TY - JOUR

T1 - Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma.

AU - Vitale, Francesco

AU - Mbisa, Georgina

AU - Cordiali-Fei, Paola

AU - Goedert, James J.

AU - Brown, Elizabeth E.

AU - Lauria, Carmela

AU - Gamache, Christine

AU - Alberg, Anthony J.

AU - Serraino, Diego

AU - Whitby, Denise

AU - Messina, Angelo

AU - Marshall, Vickie

PY - 2006

Y1 - 2006

N2 - BACKGROUND. Classic Kaposi sarcoma (CKS) is an inflammatory-mediated neoplasm that develops in the presence of KS-associated herpesvirus (KSHV) and immune perturbation. In the current study, the authors compared CKS cases with age-matched and sex-matched KSHV-seropositive controls without human immunodeficiency virus-1 infection and markers of viral control, blood counts, CD4-positive and CD8-positive lymphocytes, and serum β-2-microglobulin and neopterin levels. METHODS. Viral loads were detected using real-time amplification of the KSHV-K6 and EBV-pol genes, anti-K8.1 (lytic) titers were detected by enzyme-linked immunoadsorbent assay, and antilatent nuclear antigen (LANA) titers were detected using immunofluorescence. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using logistic regression adjusted for sex, age, and study site. RESULTS. Peripheral blood mononuclear cells (PBMC) KSHV DNA detection (P ≤ .0001) and high KSHV lytic (>1:1745; P ≤ .0001) and latent (>1:102,400; P = .03) antibody titers were found to be positively associated with CKS risk. Antibody titers were higher in cases with lesions compared with cases without lesions (P ≤ .05). The detection of Epstein-Barr virus (EBV) DNA in PBMCs was not found to be associated with CKS (P = .95). Independent of PBMC KSHV DNA, CKS risk was found to be positively associated with reduced hematocrit (<37.4%; P = .03), hemoglobin (<12g/dL; P = .04), and lymphocytes (<1000 cells/μL; P = .004), including CD4-positive (+) cells (<457 cells/μL; P = .07) and CD8+ cells (<213cells/μL; P = .04), and with increased monocytes (≥638 cells/μL; P = .009). Nonsignificant elevations of β-2-microglobulin and neopterin were observed among cases regardless of disease burden (P ≥ .08). In a multivariate model, the CKS risk was found to be associated with PBMC KSHV DNA (OR of 2.7; 95% CI, 1.4-5.3), a high KSHV lytic antibody titer (OR of 3.7; 95% CI, 1.9-7.4), and low lymphocytes, particularly among those patients age <70 years (OR of 8.0; 95% CI, 2.7-23.7). CONCLUSIONS. The findings of the current study appear to corroborate the specificity of KSHV and highlight the hematologic and immunologic correlates involved in the pathogenesis of CKS.

AB - BACKGROUND. Classic Kaposi sarcoma (CKS) is an inflammatory-mediated neoplasm that develops in the presence of KS-associated herpesvirus (KSHV) and immune perturbation. In the current study, the authors compared CKS cases with age-matched and sex-matched KSHV-seropositive controls without human immunodeficiency virus-1 infection and markers of viral control, blood counts, CD4-positive and CD8-positive lymphocytes, and serum β-2-microglobulin and neopterin levels. METHODS. Viral loads were detected using real-time amplification of the KSHV-K6 and EBV-pol genes, anti-K8.1 (lytic) titers were detected by enzyme-linked immunoadsorbent assay, and antilatent nuclear antigen (LANA) titers were detected using immunofluorescence. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using logistic regression adjusted for sex, age, and study site. RESULTS. Peripheral blood mononuclear cells (PBMC) KSHV DNA detection (P ≤ .0001) and high KSHV lytic (>1:1745; P ≤ .0001) and latent (>1:102,400; P = .03) antibody titers were found to be positively associated with CKS risk. Antibody titers were higher in cases with lesions compared with cases without lesions (P ≤ .05). The detection of Epstein-Barr virus (EBV) DNA in PBMCs was not found to be associated with CKS (P = .95). Independent of PBMC KSHV DNA, CKS risk was found to be positively associated with reduced hematocrit (<37.4%; P = .03), hemoglobin (<12g/dL; P = .04), and lymphocytes (<1000 cells/μL; P = .004), including CD4-positive (+) cells (<457 cells/μL; P = .07) and CD8+ cells (<213cells/μL; P = .04), and with increased monocytes (≥638 cells/μL; P = .009). Nonsignificant elevations of β-2-microglobulin and neopterin were observed among cases regardless of disease burden (P ≥ .08). In a multivariate model, the CKS risk was found to be associated with PBMC KSHV DNA (OR of 2.7; 95% CI, 1.4-5.3), a high KSHV lytic antibody titer (OR of 3.7; 95% CI, 1.9-7.4), and low lymphocytes, particularly among those patients age <70 years (OR of 8.0; 95% CI, 2.7-23.7). CONCLUSIONS. The findings of the current study appear to corroborate the specificity of KSHV and highlight the hematologic and immunologic correlates involved in the pathogenesis of CKS.

UR - http://hdl.handle.net/10447/18834

M3 - Article

VL - 107

SP - 2282

EP - 2290

JO - Cancer

JF - Cancer

SN - 0008-543X

ER -