Human herpesvirus-6 infection in renal allografts: retrospective immunohistochemical study in Japanese recipients

Abstract

This study was conducted to determine the incidence and clinical significance of human herpesvirus-6 (HHV-6) infection in renal allografts. A total of 105 biopsy specimens from 72 recipients were immunohistochemically examined for the presence of HHV-6 antigen, which localized in the distal tubular epithelial cells and in a few lymphocytes infiltrating into the interstitium. HHV-6 antigen in the tubular epithelia was detected in 63 (61.2%) specimens. Categorically, a higher incidence of the antigen was noted in specimens of accelerated rejection (3/4, 75.0%), acute rejection (28/3, 73.7%), and cyclosporin nephropathy (8/11, 72.7%). The antigen was present and absent an almost equal number of times in the categories of chronic rejection, intraoperative and routine protocol biopsies. Repeated biopsies were performed in six cases showing HHV-6 antigen, only one of which underwent transplant nephrectomy due to severe chronic rejection. Single or multinucleated giant cells in distal tubuli occurred in 10 (9.5%) specimens in a scattered manner. All of them were diagnosed as acute or chronic rejection. The giant cells showed no immunoreactivity for HHV-6, cytomegalovirus, or herpes simplex virus. These results indicate overall that HHV-6 infection is common in renal allografts and might be reactivated in acute rejection or cyclosporin nephropathy. The presence of HHV-6 antigen, however, does not necessarily correlate with a poor prognosis for the renal graft nor with the occurrence of giant cells in distal tubuli.

Involvement of Human Herpesvirus 6 Infection in Renal Dysfunction Associated with DIHS/DRESS

“…The role of HHV-6 infection in allograft rejection has been examined in renal transplant recipients. Helanterä et al (7) and Hoshino et al (8) showed that HHV-6 antigen was expressed in tubular cells in renal transplant recipients, but they described no clear association of HHV-6 infection with renal dysfunction. On the other hand, some researchers have suggested that reactivation of HHV-6 may induce rejection of renal transplants (9).…”

Update on Human Herpesvirus 6 Biology, Clinical Features, and Therapy

“…Clinical manifestations of HHV-6 reactivation or reinfection in SOT recipients are similar to those described in BMT patients. These include fever and/or rash as the most frequently seen disease manifestation of active HHV-6 infection (150,363,384,449,451), followed by encephalitis or encephalopathy (291,323,363,384), hepatitis (150,384,427), graft dysfunction or rejection (2,15,168,231), bone marrow suppression (362,363), and pneumonitis (362). Table 2 provides a summary of prospective studies in SOT patients.…”

Human Herpesvirus 6, 7 and 8 in Solid Organ Transplantation

“…Qualitative or quantitative HHV‐6 PCR of the cerebrospinal fluid is useful to diagnose HHV‐6 encephalitis in patients with the appropriate clinical signs . Immunohistochemistry to detect viral antigens in biopsy specimens may be more informative than viremia in cases where tissue‐invasive HHV‐6 disease is suspected . However, HHV‐6 antigen may be found commonly in tissue in the absence of symptoms .…”