Re: Re: KS risks. 27 July 2004
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Peter J Flegg,
Consultant Physician
Blackpool, UK FY3 8NR

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Re: Re: Re: KS risks.

I would like to respond to Pennee Atkinson’s queries about Kaposi's sarcoma (KS). Based on work done over the last decade it is now clear that this disease is the result of infection with a Herpes virus, HHV-8. Infection with is usually uncommon, but not rare (2% of blood donors but about 30% of gay men and black Africans). Like other Herpes group viruses, it exhibits latency. Cell types infected with HHV-8 can be induced to enter a lytic cycle, with productive reactivation of virus replication. HHV-8 possesses 4 genes with oncogenic potential and differing expression of these genes may influence the type of tumour that results (KS being only one of the possible outcomes). KS may start as a hyperplastic polyclonal lesion that later gives rise to a clonal cell population only under certain circumstances, such as immunosuppression. There are other post-transplantation lymphoproliferative disorders which are recognised, such as those related to EBV.

Essentially, KS may occur following immunosuppression, be it drug- induced for the purposes of renal (or other) transplants, or HIV-induced. There is an overall 1-2% chance of KS developing at a time point 2 to 3 years following the transplant (1). Transplant recipients with latent HHV- 8 infection have a 23% risk, compared to 0.7% in recipients with no evidence of pre-existing HHV-8 (some of these infections may have been the result of HHV-8 acquisition from the donor organ or blood transfusion) (2). It has been demonstrated that immunosuppression from renal transplantation can cause persistent HHV-8 reactivation (3); in some of these cases the end result will be clinical KS.

I hopes this helps answer Ms Atkinson's question "Why did not the original organ donors develop KS?" The problem lies with the recipients, who had latent HHV-8, which reactivated under the influence of the immunosuppressive anti-rejection regimen, and not the donors.

Perhaps it would be easier for Ms Atkins to appreciate the principle involved by looking at another latent virus, varicella-zoster. It is clear that immunosuppression (be it due to HIV, chemotherapy, or even just getting old) can result in reacivation and precipitate an attack of shingles.

The causal link with HIV-induced immunodeficiency is clear, and I hope Ms Atkinson is not trying to use the fact that one can develop KS but be "HIV negative" in order to imply HIV does not exist. Confirmation of the link is evident by the well documented finding that in the vast majority of cases of HIV-related KS, if one treats the HIV with combination HIV therapy (usually labelled as "immunosuppressive and AIDS- causing" by the dissidents), the immunodeficiency is corrected, and the KS regresses or goes into remission. So yes, to answer another of her questions, we can rule out drugs such as AZT.

REFERENCES:

1. Francès, C., C. Mouquet, and V. Calvez. Human herpesvirus 8 and renal transplantation. N. Engl. J. Med. 1999. 340:1045

2. Cattani, P., M. Capuano, R. Graffeo, R. Ricci, F. Cerimele, D. Cerimele, G. Nanni, and G. Fadda.. Kaposi's sarcoma associated with previous human herpesvirus 8 infection in kidney transplant recipients. J. Clin. Microbiol. 2001. 39:506-508.

3. Hundall, S. D., L. P. Rady, S. K. Tyring, and J. C. Fish.. Serologic and molecular evidence of human herpesvirus 8 activation in renal transplant recipients. J. Infect. Dis. 1998. 178:1791-1794.

Competing interests: None declared