TY - JOUR
AU - Durlik,, Magdalena
AB - Sir, Human herpesvirus 6 (HHV-6) is a member of the β-herpesvirinae subfamily and infects the majority of the population during the first 2 years of life. HHV-6 has been divided into HHV-6A and- 6B variants, on the basis of distinct genetic, immunological and biological characteristics [1]. In immunocompromised patients after transplantation, HHV-6 infection can be associated with a range of clinical diseases including encephalitis, bone marrow suppression, pneumonitis, hepatitis, early and late graft failure and febrile illness [2]. We report a kidney transplant with probable HHV-6A infection associated with thrombotic microangiopaty (TMA). A 44-year-old woman underwent cadaveric kidney transplantation for the second time in 2000. Post-transplant immunosuppressive regimen included methylprednisolone, mycophenolate mofetil (MMF) and daclizumab. From the sixth day after transplantation, she suffered from fever without an apparent site of infection. She developed thrombocytopaenia (97 000/mm3), elevated serum levels of LDH (609 U/l), anaemia (Hb, 8.8 g/dl), liver dysfunction (AST, –226 IU/l; ALT, −908 IU/l) and graft failure (creatinine, 2.2 mg/dl; nephrotic proteinuria, −3.5 g/daily). Renal graft biopsies that followed revealed the following abnormalities: (biopsy 1) acute rejection IIA (Banff ’97 criteria for AR); (biopsy 2 and biopsy 3) TMA. No pathogen was found in the postoperative wound, catheter cultures, blood, stool and urine cultures. CMV pp65 antigenaemia, viral isolation using the shell vial method and serological tests were negative. An active Epstein–Barr virus infection was excluded. HHV-6A was the sole pathogen, the DNA of which and IgM antibodies were detected in patient's serum. Apart from the introduction of anti-rejection therapy, gancyclovir, i.v. immunoglobulins, as well as empiric antibacterial treatment was administrated. Gancyclovir (2.5 mg/kg i.v.) was continued to day 32. Gradual improvement of graft function with a decrease of creatinine level to 1.28 mg/dl was observed. The patient's clinical status gradually improved, with resolution of thrombocytopaenia and normalization of liver function. 40 days after admission for Tx the patient was discharged. In our case, retrospective study of preserved serum using quantitative PCR analysis and serological tests revealed that HHV-6 A DNA and IgM antibodies were detected in the early post-transplant period, indicating that viral replication occurred following immunosuppressive therapy. The development of TMA was accompanied by the detection of viral HHV-6A DNA in the patient's sera and HHV-6 IgM seroconversion. Therefore, HHV-6 reactivation should be considered as the cause of TMA. We were able to exclude other potential causes of TMA, such as CMV infection, bacterial infection and treatment with calcineurin inhibitors. This finding is consistent with a previously described fact that, apart from CMV, HHV-6 is a pathogen known to infect vascular endothelial cells and could be the cause of vascular endothelial injury [3]. Thus, HHV-6 infection has been reported to play a significant pathogenic role having a stronger effect than CMV in the development of TMA after BMT and stem cell transplantation [4,5]. The association between viral infection and allograft rejection is controversial. Okuno et al. [6] suggested that HHV-6 can infect renal tissues and that the infection may be linked to rejection or to immunosuppressive therapy. In another study, vascular adhesion molecule expression was observed in liver tissues infected with HHV-6 after liver transplantation [7]. The authors suggested that this immunologic stimulation caused by the virus may be involved in or be the trigger of the rejection cascade. Wade et al. [8] reported that children rejecting their kidneys after the appearance of anti-HHV6 IgM antibodies with no prior immunity to HHV-6 appear to have extremely high risk for a virus-associated rejection, approaching 100%. This report confirms the HHV-6 variant A reactivation in a kidney transplant recipient and suggests that HHV-6 variant A reactivation may be associated with specific clinical manifestations. This case highlights the need to consider HHV-6 infection as a potential cause of post-transplant fever of unknown origin and TMA. HHV-6 infection should be taken into account in a transplant recipient presenting with a CMV-like clinical syndrome, where CMV assays are negative. Conflict of interest statement. None declared. References 1 Schirmer EC, Wyatt LS, Yamanishi K, Rodriguez WJ, Frenkel N. Differentiation between two distinct classes of viruses now classified as human herpesvirus 6. Proc Natl Acad Sci USA 1991 ; 88 : 5922 –5926 2 Dockrell DH. Human herpesvirus 6: molecular biology and clinical features. J Med Microbiol 2003 ; 52 : 5 –18 3 Takatsuka H, Wakae T, Mori A et al. Endothelial damage caused by cytomegalovirus and human herpesvirus 6. Bone Marrow Transpl 2003 ; 31 : 475 –479 4 Belford A, Myles O, Magill A, Myhand RC, Waselenko JK. Thrombotic microangiopathy (TMA) and stroke due to human herpesvirus-6 (HHV-6) reactivation in an adult receiving high-dose melphalan with autologous peripheral stem cell transplantation. Am J Hematol 2004 ; 76 : 156 –162 5 Matsuda Y, Hara J, Miyoshi H et al. Thrombotic microangiopathy associated with reactivation of human herpesvirus-6 following high-dose chemiotherapy with autologous bone marrow transplantation in young children. Bone Marrow Transpl 1999 ; 24 : 919 –923 6 Okuno T, Higashi K, Shiraki K et al. Human herpesvirus-6 in renal transplantation. Transplantation 1990 ; 49 : 519 –522 7 Lautenschlager I, Hockerstedt K, Linnavuori K, Taskinen E. Human herpesvirus 6 infection increases adhesion molecule expression in liver allografts. Transplant Proc 1999 ; 31 : 479 –480 8 Wade AW, McDonald AT, Acott PD, Lee S, Crocker JF. Human herpesvirus-6 or Epstein–Barr virus infection and acute allograft rejection in pediatric kidney transplant recipients: greater risk for immunologically naïve recipients. Transplant Proc 1998 ; 30 : 2091 –2093 © The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
TI - Human herpesvirus 6 variant A infection in renal transplant recipient
JO - Nephrology Dialysis Transplantation
DO - 10.1093/ndt/gfh992
DA - 2005-10-01
UR - https://www.deepdyve.com/lp/oxford-university-press/human-herpesvirus-6-variant-a-infection-in-renal-transplant-recipient-fLj0eVagd0
SP - 2294
EP - 2294
VL - 20
IS - 10
DP - DeepDyve
ER -