INFECTION WITH HUMAN HERPESVIRUS 8 AND TRANSPLANT-ASSOCIATED GAMMOPATHY

Background. The role of human herpesvirus (HHV)-8 in the pathogenesis of multiple myeloma and its pre-malignant state of monoclonal gammopathy is unclear. HHV-8 is transmitted by organ transplantation, representing a unique model with which to investigate primary HHV-8 infection. Methods. The authors studied the incidence of clonal gammopathy in renal transplant recipients and correlated it with previous and recent HHV-8 infection. Results. Clonal gammopathy was observed in 31 of 162 (19%) HHV-8–seronegative patients, in 5 of 17 (29%) HHV-8–seropositive patients, and in 9 of 24 (38%) HHV-8 seroconverters within 5 years after transplantation. Gammopathy was often transient, and no progression to myeloma was observed. Two patients with persistent gammopathy developed B-cell lymphoma. In a logistic regression model, HHV-8 serostatus of the graft recipient was significantly associated with subsequent development of gammopathy, with a relative risk (RR) of 1.9 and a 95% confidence interval (CI) of 0.5 to 6.4 for an HHV-8–seropositive recipient and an RR of 2.9 and a 95% CI of 1.01 to 8.0 for seroconverters as compared with baseline (HHV-8 seronegative). Other significant variables were cytomegalovirus (CMV) serostatus and the intensity of immunosuppression (RR of 10.4 and 95% CI of 2.6–41.7 for a CMV-negative recipient with a CMV-positive donor vs. a CMV-negative recipient with a CMV-negative donor and RR of 17.6 and 95% CI of 2.0–150.8 if OKT3 was used vs. no use of antilymphocytic substances). Conclusions. Transplant recipients with HHV-8 infection are more likely to develop clonal gammopathy. However, this risk is much lower than the risk conferred by CMV infection and antilymphocytic therapy, arguing against a major role of HHV-8 infection in the pathogenesis of clonal plasma cell proliferation.

[1]  C. Mecucci,et al.  Post-transplant Kaposi sarcoma originates from the seeding of donor-derived progenitors , 2003, Nature Medicine.

[2]  D. Samuel,et al.  Detection of gammopathy by serum protein electrophoresis for predicting and managing therapy of lymphoproliferative disorder in 911 recipients of liver transplants. , 2001, Blood.

[3]  T. Schulz,et al.  Bone marrow failure associated with human herpesvirus 8 infection after transplantation. , 2000, The New England journal of medicine.

[4]  T. Schulz,et al.  Molecular evidence of organ-related transmission of Kaposi sarcoma-associated herpesvirus or human herpesvirus-8 in transplant patients. , 2000, Blood.

[5]  R. Kyle,et al.  Lack of serologic association of human herpesvirus-8 (KSHV) in patients with monoclonal gammopathy of undetermined significance with and without progression to multiple myeloma. , 2000, Blood.

[6]  H. Einsele,et al.  Absence Of Human Herpesvirus 8 Dna Sequences In Leucapheresis Products And Bone Marrow Samples Of Patients With Advanced Multiple Myeloma , 2000, British journal of haematology.

[7]  P. Brousset,et al.  KAPOSI'S SARCOMA‐ASSOCIATED HERPESVIRUS (KSHV) IN BONE MARROW BIOPSY FROM PATIENTS WITH MULTIPLE MYELOMA: PCR AMPLIFICATION OF ORF26 BUT NOT ORF72 AND ORF75 SEQUENCES , 2000, British journal of haematology.

[8]  E. Lennette,et al.  Serologic Prevalence of Antibody to Human Herpesvirus Type 8 in Patients with Various Monoclonal Gammopathies , 2000, Leukemia & lymphoma.

[9]  E. Kieff,et al.  Epstein-barr virus-induced posttransplant lymphoproliferative disorders , 1999 .

[10]  J. Pirsch Cytomegalovirus infection and posttransplant lymphoproliferative disease in renal transplant recipients: results of the U.S. multicenter FK506 Kidney Transplant Study Group. , 1999, Transplantation.

[11]  M. Wernli,et al.  Transmission of human herpesvirus 8 infection from renal-transplant donors to recipients. , 1998, The New England journal of medicine.

[12]  K. Tarte,et al.  Evidence against KSHV infection in the pathogenesis of multiple myeloma. , 1998, Virus research.

[13]  G. Pinkus,et al.  Localization of Kaposi's sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma. , 1997, Blood.

[14]  M. Moroni,et al.  Risk of Kaposi's sarcoma-associated herpes virus transmission from donor allografts among Italian posttransplant Kaposi's sarcoma patients. , 1997, Blood.

[15]  J. Said,et al.  Kaposi's sarcoma-associated herpesvirus infection of bone marrow dendritic cells from multiple myeloma patients. , 1997, Science.

[16]  H. Bock,et al.  Monoclonal gammopathy after intense induction immunosuppression in renal transplant patients. , 1996, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[17]  P. Simmonds,et al.  Prevalence of Kaposi's sarcoma associated herpesvirus infection measured by antibodies to recombinant capsid protein and latent immunofluorescence antigen , 1996, The Lancet.

[18]  P. Moore,et al.  Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma in patients with and those without HIV infection. , 1995, The New England journal of medicine.

[19]  G Opelz,et al.  Feeding the preterm infant , 1993, The Lancet.

[20]  J. Preiksaitis,et al.  Is sequential use of ALG and OKT3 in renal transplants associated with an increased incidence of fulminant posttransplant lymphoproliferative disorder? , 1991, Transplantation proceedings.

[21]  R. Fisher,et al.  Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients. , 1990, The New England journal of medicine.

[22]  A. Fischer,et al.  PROSPECTIVE STUDY OF THE OCCURRENCE OF MONOCLONAL GAMMAPATHIES FOLLOWING BONE MARROW TRANSPLANTATION IN YOUNG CHILDREN , 1990, Transplantation.

[23]  A. Sheil,et al.  Immunoglobulin abnormalities in renal transplant recipients. , 1989, Transplantation.

[24]  D. Rush,et al.  Monoclonal and multiclonal gammopathies after renal transplantation. , 1989, Transplantation proceedings.

[25]  B. Griffith,et al.  Epstein-Barr virus infections and DNA hybridization studies in posttransplantation lymphoma and lymphoproliferative lesions: the role of primary infection. , 1985, The Journal of infectious diseases.

[26]  R. Valentijn,et al.  Monoclonal gammapathies in patients undergoing immunosuppressive treatment after renal transplantation. , 1985, Clinical immunology and immunopathology.

[27]  R. Bataille,et al.  Qualitative and quantitative analysis of human herpesviruses in chronic and acute B cell lymphocytic leukemia and in multiple myeloma , 2003, Leukemia.

[28]  E. Kieff,et al.  Epstein-Barr virus-induced posttransplant lymphoproliferative disorders. ASTS/ASTP EBV-PTLD Task Force and The Mayo Clinic Organized International Consensus Development Meeting. , 1999, Transplantation.

[29]  M. V. van Tol,et al.  Immunoglobulin levels and monoclonal gammopathies in children after bone marrow transplantation. , 1993, Blood.