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.
Regamey
Nicolas
N
University Children's Hospital of Bern, Freiburgstr. 15, CH-3010 Bern, Switzerland. nicolas.regamey@insel.ch
Hess
Viviane
V
Passweg
Jakob
J
Hess
Christoph
C
Steiger
Jürg
J
Erb
Peter
P
Cathomas
Gieri
G
Tamm
Michael
M
D000961:Antilymphocyte Serum / Q000009:adverse effects; D003586:Cytomegalovirus Infections / Q000150:complications / Q000453:epidemiology / Q000209:etiology; D006566:Herpesviridae Infections / Q000150:complications* / Q000453:epidemiology / Q000209:etiology; D019288:Herpesvirus 8, Human / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D015994:Incidence; D016030:Kidney Transplantation / Q000009:adverse effects*; D016015:Logistic Models; D016853:Muromonab-CD3 / Q000009:adverse effects; D010265:Paraproteinemias / Q000150:complications* / Q000453:epidemiology / Q000209:etiology*; D012306:Risk; D014019:Tissue Donors; D014775:Virus Activation
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3