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.
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Ablashi DV, Salahuddin SZ, Josephs SF, Imam F, Lusso P, Gallo RC (1987) HBLV (or HHV-6) in human cell lines. Nature 329: 207
Asano Y, Yoshikawa T, Suga S, Yazaki T, Hirabayashi S, Ono Y, Tsuzuki K, Oshima S (1989) Human herpesvirus 6 harbouring in kidney (letter). Lancet II: 1391
Asano Y, Yoshikawa T, Suga S, Nakashima T, Yazaki T, Fukuda M, Kojima S, Matsuyama T (1991) Reactivation of herpesvirus type 6 in children receiving bone marrow transplantation for leukemia. N Engl J Med 324: 634–635
Biberfeld P, Kramarsky B, Salahuddin SZ, Gallo RC (1987) Ultrastructural characterization of a new human B lymphotropic DNA virus (human herpesvirus 6) isolated from patients with lymphoproliferative disease. J Natl Cancer Inst 79: 933–941
Carrigan DR, Drobyski WR, Russler SK, Tapper MA, Knox KK, Ash RC (1991) Interstitial pneumonitis associated with human herpesvirus-6 infection after marrow transplantation. Lancet 338: 147–149
Cone RW, Hackman RC, Huang MW, Bowden RA, Meyers JD, Metcalf M, Zeh J, Ashley R, Corey L (1993) Human herpesvirus 6 in lung tissue from patients with pneumonitis after bone marrow transplantation. N Engl J Med 329: 156–161
Eizuru Y, Minematsu T, Minamishima Y, Kikuchi M, Yamanishi K, Takahashi M, Kurata T (1989) Human herpesvirus 6 in lymph nodes. Lancet I: 40–41
Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29: 577–580
Josephs SF, Salahuddin SZ, Ablashi DV, Schachter F, Wong-Staal F, Gallo RC (1986) Genomic analysis of the human B-lymphotropic virus (HBLV). Science 234: 601–603
Kikuta H, Itami N, Matsumoto S, Chikaraishi T, Togashi M (1991) Frequent detection of human herpesvirus 6 DNA in peripheral blood mononuclear cells from kidney transplant patients. J Infect Dis 163: 925
Kondo K, Kondo T, Okuno T, Takahashi M, Yamanishi K (1991) Latent human herpesvirus 6 infection of human monocytes/macrophages. J Gen Virol 72: 1401–1408
Kurata T, Iwasaki T, Sata T, Wakabayashi T, Yamaguchi K, Okuao T, Yamanishi K, Takei Y (1990) Viral pathology of human herpesvirus 6 infection. In: Lopez C, Mori R, Roizman B, Whitly RW (eds) Immunobiology and prophylaxis of human herpesvirus infections. Advances in experimental medicine and biology. Plenum Press, New York, pp 39–47
Luka J, Okano M, Thiele G (1990) Isolation of human herpesvirus-6 from clinical specimens using human fibroblast cultures. J Clin Lab Anal 4: 483–486
Lusso P, Markham PD, Tschachler E, di Marzo Veronese F, Salahuddin SZ, Ablashi DV, Pahwa S, Krohn K, Gallo RC (1988) In vitro cellular tropism of human B-lymphotropic virus (human herpesvirus-6). J Exp Med 167: 1659–1670
Lusso P, Gallo RC (1994) Human herpesvirus 6 in AIDS. Lancet 343: 555–556
Merlino C, Giacchino F, Segoloni GP, Ponzi AN (1992) Human herpesvirus-6 infection and renal transplantation. Transplantation 53: 1382–1383
Morris DJ, Littler E, Arrand JR, Jordan D (1989) Human herpesvirus 6 infection in renal transplant recipients. N Engl J Med 320: 1560–1561
Okuno T, Higashi K, Shiraki K, Yamanishi K, Takahashi M, Kokado Y, Ishibashi M, Takahara S, Sonoda T, Tanaka K, Baba K, Yabuuchi H, Kurata T (1990) Human herpesvirus 6 infection in renal transplantation. Transplantation 49: 519–522
Okuno T, Sao H, Asada H, Shiraki K, Takahashi M, Yamanishi K (1990) Analysis of a glycoprotein of human herpesvirus 6 (HHV-6) using monoclonal antibodies. Virology 176: 625–628
Okuno T, Shao H, Asada H, Shiraki K, Takahashi M, Yamanishi K (1992) Analysis of human herpesvirus 6 glycoproteins recognized by monoclonal antibody OHV1. J Gen Virol 73: 443–447
Salahuddin SZ, Ablashi DV, Markham PD, Josephs SF, Sturzenegger S, Kaplan M, Halligan G, Biberfeld P, Wong-Staal F, Kramarsky B, Gallo RC (1986) Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science 234: 596–601
Sanfilippo F (1990) Renal transplantation. In: Sale GE (ed) The pathology of organ transplantation. Butterworths, Boston London Singapore, pp 51–101
Takahashi K, Sonoda S, Higashi K, Kondo T, Takahashi H, Takahashi M, Yamanishi K (1989) Predominant CD4 T-lymphocytes tropism of human herpesvirus 6-related virus. J Virol 63: 3161–3163
Wakabayashi T (1993) The pathology of the transplanted kidney (in Japanese). Pathology and Clinical Medicine 11: 428–433
Ward KN, Gray JJ, Efstathiou S (1989) Primary human herpesvirus 6 infection in a patient following liver transplantation from a seronegative donor. J Med Virol 28: 69–72
Ward KN, Gray JJ, Fotheringham MW, Sheldon MJ (1993) IgG antibodies to human herpesvirus-6 in young children: changes in avidity of antibody correlate with time after infection. J Med Virol 39: 131–138
Wrzos H, Gibbons J, Abt PL, Gifford RRM, Yang HC (1990) Human herpesvirus 6 in monocytes of transplant patients. Lancet 335: 486–487
Yamanishi K, Okuno T, Shiraki K, Takahashi M, Kondo T, Asano Y, Kurata T (1988) Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet I: 1065–1067
Yoshikawa T, Suga S, Asano Y, Nakashima T, Yazaki T, Ono Y, Fujita T, Tsuzuki K, Sugiyama S, Oshima S (1992) A prospective study of human herpesvirus-6 infection in renal transplantation. Transplantation 54: 879–883
Zollinger HU, Mihatsch MJ (1978) Renal pathology in biopsy. Springer, Berlin Heidelberg New York
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Hoshino, K., Nishi, T., Adachi, H. et al. Human herpesvirus-6 infection in renal allografts: retrospective immunohistochemical study in Japanese recipients. Transpl Int 8, 169–173 (1995). https://doi.org/10.1007/BF00336532
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DOI: https://doi.org/10.1007/BF00336532