Human herpes virus-8 and other risk factors for Kaposi's sarcoma in kidney transplant recipients. Groupe Cooperatif de Transplantation d' Ile de France (GCIF).
BACKGROUND
The exact reasons for the high incidence of Kaposi's sarcoma (KS) after kidney transplantation are still unknown. Immunosuppression is classically considered as the main risk factor, but the relative risk contributed by the patient's geographic origin and by human herpes virus (HHV)-8 infection still has to be determined.


METHODS
We carried out a retrospective and a prospective study among kidney transplant recipients (TP) to identify the risk factors for posttransplantation KS. Each of 30 KS patients was matched with two controls to investigate 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 viremia in response to decreased immunosuppression.


RESULTS
African and Middle East origins, past infection with hepatitis B, hemoglobin level <12 g/dl, lymphocyte count <750/mm3 at the time of diagnosis and initial use of polyclonal antilymphocyte sera were risk factors for 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 transplantation developed KS compared with 3% (1/33) of seronegative TP (P<0.00001). HHV-8 DNA was detectable in seven of nine peripheral blood mononuclear cells (PBMC) and in six of six KS lesions at diagnosis; it became negative in PBMC in three of five patients in parallel with tumor regression.


CONCLUSIONS
African and Middle East geographic origins, HHV-8 infection before and after kidney transplantation, and initial use of polyclonal antilymphocyte sera were independent risk factors for KS. The presence of HHV-8 antibodies before or after transplantation was highly predictive of the emergence 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 DNA within PBMC and KS lesions seems related to tumor burden and evolution.
Farge
D
D
Hopital Saint-Louis, Paris, France. d.farge@chu-stlouis-fr
Lebbé
C
C
Marjanovic
Z
Z
Tuppin
P
P
Mouquet
C
C
Peraldi
M N
MN
Lang
P
P
Hiesse
C
C
Antoine
C
C
Legendre
C
C
Bedrossian
J
J
Gagnadoux
M F
MF
Loirat
C
C
Pellet
C
C
Sheldon
J
J
Golmard
J L
JL
Agbalika
F
F
Schulz
T F
TF
D000328:Adult; D000349:Africa / Q000208:ethnology; D000914:Antibodies, Viral / Q000097:blood; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood / Q000378:metabolism; D005260:Female; D005602:France / Q000453:epidemiology; D006566:Herpesviridae Infections / Q000097:blood / Q000150:complications* / Q000821:virology; D019288:Herpesvirus 8, Human; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D008877:Middle East / Q000208:ethnology; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D012514:Sarcoma, Kaposi / Q000209:etiology* / Q000821:virology*; D019562:Viral Load; D014766:Viremia / Q000097:blood / Q000821:virology
D000914:Antibodies, Viral; D000961:Antilymphocyte Serum; D004279:DNA, Viral; D007166:Immunosuppressive Agents