Human herpes virus-8 and other risk factors for Kaposi's sarcoma in kidneytransplant recipients

Background. The exact reasons for the high incidence of Kaposi's sarcoma (K S) after kidney transplantation are still unknown. Immunosuppression is cla ssically considered as the main risk factor, but the relative risk contribu ted by the patient's geographic origin and by human herpes virus (HHV)-8 in fection still has to be determined. Methods. We carried out a retrospective and a prospective study among kidne y transplant recipients (TP) to identify the risk factors for posttransplan tation KS. Each of 30 KS patients was matched with two controls to investig ate the association with geographic origin, immunosuppressive regimen, HHV- 8 antibodies before and after transplantation, and other infections. Among TP with new onset of KS, we prospectively evaluated HHV-8 serology and vire mia in response to decreased immunosuppression. Results. African and Middle East origins, past infection with hepatitis B, hemoglobin level <12 g/dl, lymphocyte count <750/mm(3) at the time of diagn osis and initial use of polyclonal antilymphocyte sera were risk factors fo r KS, After multivariate analysis, origin in Africa or Middle East and use of antilymphocyte sera for induction remained as independent risk factors. Sixty-eight percent (17/25) of TP with HHV-8 antibodies before or after tra nsplantation developed KS compared with 3% (1/33) of seronegative TP (P<0.0 0001). HHV-8 DNA was detectable in seven of nine peripheral blood mononucle ar cells (PBMC) and in six of six KS lesions at diagnosis; it became negati ve in PBMC in three of five patients in parallel with tumor regression. Conclusion. African and Middle East geographic origins, HHV-8 infection bef ore and after kidney transplantation, and initial use of polyclonal antilym phocyte sera were independent risk factors for KS. The presence of HHV-8 an tibodies before or after transplantation was highly predictive of the emerg ence of posttransplantation KS and conferred a 28-fold increased risk of KS (odds ratio=28.4; 95% confidence interval: 4.9-279), Detection of HHV-8 DN A within PBMC and KS lesions seems related to tumor burden and evolution.