Correspondence

HHV-8 Peripheral-Blood Viral Load and the Titer of Antibodies against HHV-8

N Engl J Med 1999; 341:1241-1242October 14, 1999

Article

To the Editor:

In their letter to the editor, Sitas et al. (June 17 issue)1 report a relation between the titers of anti–human herpesvirus 8 (HHV-8) antibodies in mothers and the prevalence of anti–HHV-8 antibodies in their children. The authors explain this relation by suggesting that high titers of antibodies against HHV-8 indicate a large number of HHV-8–infected cells in the peripheral blood (i.e., a large viral load). Likewise, in their editorial in the same issue, Jaffe and Pellett2 suggest that the correlation between high titers of HHV-8 antibodies and an increased risk of Kaposi's sarcoma, reported by Sitas et al. in a separate article in the June 17 issue,3 reflects an increase in the viral load in persons with Kaposi's sarcoma. We present preliminary data that contradict this proposed relation between the titer of antibodies against HHV-8 and the HHV-8 viral load.

We obtained a single blood specimen from each of 26 patients in Harare, Zimbabwe, who were infected with the human immunodeficiency virus (HIV) and had histologically confirmed Kaposi's sarcoma. The titer of antibodies against the latent nuclear antigen of HHV-8 was determined with the use of the BCP-1 cell line and an immunofluorescence assay 4 that is similar to the antibody assay used by Sitas et al.3 The amount of HHV-8 DNA present in plasma and peripheral-blood mononuclear cells from each patient was determined by a quantitative kinetic polymerase-chain-reaction (PCR) assay. The kinetic PCR assay used for this analysis has a linear dynamic range of 300 to 1 million copies per milliliter for the quantitation of HHV-8 DNA in plasma and 5 to 100,000 copies per microgram of peripheral-blood mononuclear cell DNA for the quantitation of HHV-8 DNA in peripheral-blood mononuclear cells (unpublished data). We found no relation between the titer of antibodies against the latent nuclear antigen of HHV-8 and the amount of HHV-8 DNA in plasma or peripheral-blood mononuclear cells (P=0.93 and P=0.49, respectively, by Spearman's rank correlation) (Figure 1Figure 1Relation between the Peripheral-Blood Human Herpesvirus 8 (HHV-8) Viral Load and the Titer of Antibodies against the Latent Nuclear Antigen (LANA) of HHV-8.). Although the results of this preliminary analysis of a small group of HHV-8–infected patients does not exclude the possibility that in some settings there is a relation between the titer of antibodies against HHV-8 and the peripheral-blood HHV-8 viral load, our findings provide evidence that the titer of antibodies against the latent nuclear antigen of HHV-8 is not a marker of the peripheral-blood HHV-8 viral load in persons with AIDS-related Kaposi's sarcoma.

Thomas B. Campbell, M.D.
University of Colorado Health Sciences Center, Denver, CO 80262

Margaret Borok, M.B., Ch.B.
Lovemore Gwanzura, Ph.M.
University of Zimbabwe School of Medicine, Harare, Zimbabwe

4 References

1. 1

   Sitas F, Newton R, Boshoff C. Increasing probability of mother-to-child transmission of HHV-8 with increasing maternal antibody titer for HHV-8. N Engl J Med 1999;340:1923-1923
   Full Text | Web of Science | Medline

2. 2

   Jaffe HW, Pellett PE. Human herpesvirus 8 and Kaposi's sarcoma -- some answers, more questions. N Engl J Med 1999;340:1912-1913
   Full Text | Web of Science | Medline

3. 3

   Sitas F, Carrara H, Beral V, et al. Antibodies against human herpesvirus 8 in black South African patients with cancer. N Engl J Med 1999;340:1863-1871
   Full Text | Web of Science | Medline

4. 4

   Gao SJ, Kingsley L, Li M, et al. KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma. Nat Med 1996;2:925-928
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors and a colleague reply:

To the Editor: Campbell and colleagues investigated the correlation between titers of anti–HHV-8 antibodies and the viral load in a small group of HIV-infected patients with Kaposi's sarcoma. In other studies of HIV-positive patients, HHV-8 was more readily detected by PCR in peripheral-blood cells from patients with Kaposi's sarcoma than in peripheral-blood cells from those without Kaposi's sarcoma,1 suggesting that the patients with Kaposi's sarcoma had an increased HHV-8 viral load. Titers of anti–HHV-8 antibodies are also higher in HIV-positive patients with Kaposi's sarcoma than in HIV-positive patients without Kaposi's sarcoma.2 Therefore, there appears to be an association between the viral load and the antibody titer.

Anti–HHV-8 antibodies are detectable in a higher percentage of patients with classic Kaposi's sarcoma (those without HIV infection) than patients with AIDS-related Kaposi's sarcoma,3,4 suggesting that some patients with Kaposi's sarcoma and AIDS have reduced or undetectable antibody responses against the latent nuclear antigen of HHV-8. Furthermore, patients with classic Kaposi's sarcoma have higher titers of anti–HHV-8 antibodies than patients with AIDS and Kaposi's sarcoma.4 Antiretroviral and antiherpesviral drugs used in HIV-infected patients may directly or indirectly (through the restoration of cellular immunity) influence the HHV-8 load, the titer of anti–HHV-8 antibodies, or both, although it is unlikely that these drugs would be readily accessible in Zimbabwe. The correlation between the titer of anti–HHV-8 antibodies and HHV-8 load may therefore not be apparent in small groups of HIV-infected patients with Kaposi's sarcoma, especially if they have been ill with HIV infection and Kaposi's sarcoma for unspecified periods.

In the study of mother-to-child transmission,5 all the subjects were mothers and children who were attending a paternity-dispute clinic but whose HIV status was unknown. Whether there is a direct correlation between the titer and the viral load in HIV-negative persons, as we hypothesized, still needs to be determined.

Dimitra Bourboulia, M.Sc.
Chris Boshoff, M.R.C.P., Ph.D.
University College London, London W1P 6BT, United Kingdom

Freddy Sitas, D.Phil.
South African Institute for Medical Research, Johannesburg 2000, South Africa

5 References

1. 1

   Whitby D, Howard MR, Tenant-Flowers M, et al. Detection of Kaposi sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma. Lancet 1995;346:799-802
   CrossRef | Web of Science | Medline

2. 2

   Sitas F, Carrara H, Beral V, et al. Antibodies against human herpesvirus 8 in black South African patients with cancer. N Engl J Med 1999;340:1863-1871
   Full Text | Web of Science | Medline

3. 3

   Gao SJ, Kingsley L, Li M, et al. KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma. Nat Med 1996;2:925-928
   CrossRef | Web of Science | Medline

4. 4

   Chatlynne LG, Ablashi DV. Seroepidemiology of Kaposi's sarcoma-associated herpesvirus (KSHV). Semin Cancer Biol 1999;9:175-185
   CrossRef | Web of Science | Medline

5. 5

   Sitas F, Newton R, Boshoff C. Increasing probability of mother-to-child transmission of HHV-8 with increasing maternal antibody titer for HHV-8. N Engl J Med 1999;340:1923-1923
   Full Text | Web of Science | Medline

Citing Articles (5)

Citing Articles

1. 1

   C. Simonelli, R. Tedeschi, A. Gloghini, R. Talamini, M.T. Bortolin, M. Berretta, M. Spina, S. Morassut, E. Vaccher, P. De Paoli, A. Carbone, U. Tirelli. (2009) Plasma HHV-8 viral load in HHV-8-related lymphoproliferative disorders associated with HIV infection. Journal of Medical Virology 81:5, 888-896
   CrossRef

2. 2

   Cecilia Simonelli, Rosamaria Tedeschi, Annunziata Gloghini, Maria Teresa Bortolin, Michele Spina, Ettore Bidoli, Roberta Cinelli, Paolo De Paoli, Antonino Carbone, Umberto Tirelli. (2005) Characterization of Immunologic and Virological Parameters in HIV‐Infected Patients with Primary Effusion Lymphoma during Antiblastic Therapy and Highly Active Antiretroviral Therapy. Clinical Infectious Diseases 40:7, 1022-1027
   CrossRef

3. 3

   Robert Newton, John Ziegler, Dimitra Bourboulia, Delphine Casabonne, Valerie Beral, Edward Mbidde, Lucy Carpenter, Gillian Reeves, D. Maxwell Parkin, Henry Wabinga, Sam Mbulaiteye, Harold Jaffe, , Robin Weiss, Chris Boshoff. (2003) The sero-epidemiology of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in adults with cancer in Uganda. International Journal of Cancer 103:2, 226-232
   CrossRef

4. 4

   S. David Hudnall, Tiansheng Chen, Peter Rady, Stephen Tyring, Paul Allison. (2003) Human herpesvirus 8 seroprevalence and viral load in healthy adult blood donors. Transfusion 43:1, 85-90
   CrossRef

5. 5

   Thomas B. Campbell, Margaret Borok, Lovemore Gwanzura, Samantha MaWhinney, Irene E. White, Buxton Ndemera, Ivy Gudza, Lisa Fitzpatrick, Robert T. Schooley. (2000) Relationship of human herpesvirus 8 peripheral blood virus load and Kaposi's sarcoma clinical stage. AIDS 14:14, 2109-2116
   CrossRef