Skip to main content
NCBI home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2003 Aug;74(8):1080–1084. doi: 10.1136/jnnp.74.8.1080

Post-transplantation HTLV-1 myelopathy in three recipients from a single donor

J Imirizaldu, J Esteban, I Axpe, T Concha, F Juanes, I Susaeta, J Carranceja
PMCID: PMC1738581  PMID: 12876238

Abstract

Objectives: This paper reports for the first time three cases of infection by HTLV-I via organ transplantation; all the organs coming from the same asymptomatic infected donor. The need is considered for the implementation of compulsory screenings for HTLV antibodies on organ donors and on blood banks.

Methods: The determination of antibodies for HTLV-I/II on samples of serum and cerebral spinal fluid from the patients and the donor was performed by enzyme immunoassay and western blot. Analysis of proviral DNA was performed by polymerase chain reaction. To detect changes in the sequence of aminoacids, the tax gene was sequentiated, amplified, and compared with ATK prototype stocks. Spinal cord magnetic resonance imaging, cerebral spinal fluid, and somatosensory evoked potential studies were carried out in all patients.

Results: All three transplanted patients developed a myelopathy within a very short period of time. In all three patients and donor the virus belonged to the Cosmopolitan A subtype. The homology of HTLV-I sequences recovered from the patients and donor was 100% in all four cases. Proviral load was high in all three patients. The factors that certainly contributed to the infection in the first place, and the development of the disease later, were on the one hand the high proviral load and their immunosupressed condition, and on the other the virus genotype, which proved to be an aggresive variant. However, the analysis of the histocompatibility antigen showed that two of the patients carried an haplotype that has been associated with a lower risk of developing this disease.

Conclusions: It is argued that, although in Spain and other European countries there is not compulsory screening for HTLV antibodies because of the studies that show a low seroprevalence, in view of the cases here reported, and to avoid the serious consequences that such infection has on transplanted patients, compulsory screenings, both on organ donors and on blood banks, should be implemented.

Full Text

The Full Text of this article is available as a PDF (131.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aye M. M., Matsuoka E., Moritoyo T., Umehara F., Suehara M., Hokezu Y., Yamanaka H., Isashiki Y., Osame M., Izumo S. Histopathological analysis of four autopsy cases of HTLV-I-associated myelopathy/tropical spastic paraparesis: inflammatory changes occur simultaneously in the entire central nervous system. Acta Neuropathol. 2000 Sep;100(3):245–252. doi: 10.1007/s004019900170. [DOI] [PubMed] [Google Scholar]
  2. Bangham C. R. HTLV-1 infections. J Clin Pathol. 2000 Aug;53(8):581–586. doi: 10.1136/jcp.53.8.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Couroucé A. M., Pillonel J., Lemaire J. M., Maniez M., Brunet J. B. Seroepidemiology of HTLV-I/II in universal screening of blood donations in France. AIDS. 1993 Jun;7(6):841–847. doi: 10.1097/00002030-199306000-00013. [DOI] [PubMed] [Google Scholar]
  4. Delaporte E., Monplaisir N., Louwagie J., Peeters M., Martin-Prével Y., Louis J. P., Trebucq A., Bedjabaga L., Ossari S., Honoré C. Prevalence of HTLV-I and HTLV-II infection in Gabon, Africa: comparison of the serological and PCR results. Int J Cancer. 1991 Sep 30;49(3):373–376. doi: 10.1002/ijc.2910490310. [DOI] [PubMed] [Google Scholar]
  5. Dumas M., Houinato D., Verdier M., Zohoun T., Josse R., Bonis J., Zohoun I., Massougbodji A., Denis F. Seroepidemiology of human T-cell lymphotropic virus type I/II in Benin (West Africa). AIDS Res Hum Retroviruses. 1991 May;7(5):447–451. doi: 10.1089/aid.1991.7.447. [DOI] [PubMed] [Google Scholar]
  6. Furukawa Y., Yamashita M., Usuku K., Izumo S., Nakagawa M., Osame M. Phylogenetic subgroups of human T cell lymphotropic virus (HTLV) type I in the tax gene and their association with different risks for HTLV-I-associated myelopathy/tropical spastic paraparesis. J Infect Dis. 2000 Sep 22;182(5):1343–1349. doi: 10.1086/315897. [DOI] [PubMed] [Google Scholar]
  7. Gessain A., Barin F., Vernant J. C., Gout O., Maurs L., Calender A., de Thé G. Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet. 1985 Aug 24;2(8452):407–410. doi: 10.1016/s0140-6736(85)92734-5. [DOI] [PubMed] [Google Scholar]
  8. Gout O., Baulac M., Gessain A., Semah F., Saal F., Périès J., Cabrol C., Foucault-Fretz C., Laplane D., Sigaux F. Rapid development of myelopathy after HTLV-I infection acquired by transfusion during cardiac transplantation. N Engl J Med. 1990 Feb 8;322(6):383–388. doi: 10.1056/NEJM199002083220607. [DOI] [PubMed] [Google Scholar]
  9. Hernandez Ramirez P., Rivero Jimenez R., Ballester Santovenia M., Navea Leyva L., Matutes E., Catovsky D., Yamaguchi K., Fukuyoshi Y., Nishimura Y., Kiyokawa T. Very low seroprevalence of HTLV-I/II in Cuba: antibodies in blood donors and in hematological and nonhematological patients. Vox Sang. 1991;61(4):277–278. doi: 10.1111/j.1423-0410.1991.tb00960.x. [DOI] [PubMed] [Google Scholar]
  10. Hino S., Yamaguchi K., Katamine S., Sugiyama H., Amagasaki T., Kinoshita K., Yoshida Y., Doi H., Tsuji Y., Miyamoto T. Mother-to-child transmission of human T-cell leukemia virus type-I. Jpn J Cancer Res. 1985 Jun;76(6):474–480. [PubMed] [Google Scholar]
  11. Izumo S., Goto I., Itoyama Y., Okajima T., Watanabe S., Kuroda Y., Araki S., Mori M., Nagataki S., Matsukura S. Interferon-alpha is effective in HTLV-I-associated myelopathy: a multicenter, randomized, double-blind, controlled trial. Neurology. 1996 Apr;46(4):1016–1021. doi: 10.1212/wnl.46.4.1016. [DOI] [PubMed] [Google Scholar]
  12. Jeffery K. J., Siddiqui A. A., Bunce M., Lloyd A. L., Vine A. M., Witkover A. D., Izumo S., Usuku K., Welsh K. I., Osame M. The influence of HLA class I alleles and heterozygosity on the outcome of human T cell lymphotropic virus type I infection. J Immunol. 2000 Dec 15;165(12):7278–7284. doi: 10.4049/jimmunol.165.12.7278. [DOI] [PubMed] [Google Scholar]
  13. Jeffery K. J., Usuku K., Hall S. E., Matsumoto W., Taylor G. P., Procter J., Bunce M., Ogg G. S., Welsh K. I., Weber J. N. HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3848–3853. doi: 10.1073/pnas.96.7.3848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jeffery K. J., Usuku K., Hall S. E., Matsumoto W., Taylor G. P., Procter J., Bunce M., Ogg G. S., Welsh K. I., Weber J. N. HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3848–3853. doi: 10.1073/pnas.96.7.3848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kamihira S., Nakasima S., Oyakawa Y., Moriuti Y., Ichimaru M., Okuda H., Kanamura M., Oota T. Transmission of human T cell lymphotropic virus type I by blood transfusion before and after mass screening of sera from seropositive donors. Vox Sang. 1987;52(1-2):43–44. doi: 10.1111/j.1423-0410.1987.tb02987.x. [DOI] [PubMed] [Google Scholar]
  16. Kaplan J. E., Osame M., Kubota H., Igata A., Nishitani H., Maeda Y., Khabbaz R. F., Janssen R. S. The risk of development of HTLV-I-associated myelopathy/tropical spastic paraparesis among persons infected with HTLV-I. J Acquir Immune Defic Syndr. 1990;3(11):1096–1101. [PubMed] [Google Scholar]
  17. Kira J., Fujihara K., Itoyama Y., Goto I., Hasuo K. Leukoencephalopathy in HTLV-I-associated myelopathy/tropical spastic paraparesis: MRI analysis and a two year follow-up study after corticosteroid therapy. J Neurol Sci. 1991 Nov;106(1):41–49. doi: 10.1016/0022-510x(91)90192-a. [DOI] [PubMed] [Google Scholar]
  18. Lillo F., Varnier O. E., Sabbatani S., Ferro A., Mendez P. Detection of HTLV-I and not HTLV-II infection in Guinea Bissau (west Africa) J Acquir Immune Defic Syndr. 1991;4(5):541–542. [PubMed] [Google Scholar]
  19. Lleó A., Planella M., Domingo P. Mielopatía e infección por el virus de la inmunodeficiencia humana. Med Clin (Barc) 1999 Mar 27;112(11):423–427. [PubMed] [Google Scholar]
  20. Manns A., Hisada M., La Grenade L. Human T-lymphotropic virus type I infection. Lancet. 1999 Jun 5;353(9168):1951–1958. doi: 10.1016/s0140-6736(98)09460-4. [DOI] [PubMed] [Google Scholar]
  21. Manns A., Miley W. J., Wilks R. J., Morgan O. S., Hanchard B., Wharfe G., Cranston B., Maloney E., Welles S. L., Blattner W. A. Quantitative proviral DNA and antibody levels in the natural history of HTLV-I infection. J Infect Dis. 1999 Nov;180(5):1487–1493. doi: 10.1086/315088. [DOI] [PubMed] [Google Scholar]
  22. Manns A., Wilks R. J., Murphy E. L., Haynes G., Figueroa J. P., Barnett M., Hanchard B., Blattner W. A. A prospective study of transmission by transfusion of HTLV-I and risk factors associated with seroconversion. Int J Cancer. 1992 Jul 30;51(6):886–891. doi: 10.1002/ijc.2910510609. [DOI] [PubMed] [Google Scholar]
  23. Morofuji-Hirata M., Kajiyama W., Nakashima K., Noguchi A., Hayashi J., Kashiwagi S. Prevalence of antibody to human T-cell lymphotropic virus type I in Okinawa, Japan, after an interval of 9 years. Am J Epidemiol. 1993 Jan 1;137(1):43–48. doi: 10.1093/oxfordjournals.aje.a116600. [DOI] [PubMed] [Google Scholar]
  24. Mueller N., Okayama A., Stuver S., Tachibana N. Findings from the Miyazaki Cohort Study. J Acquir Immune Defic Syndr Hum Retrovirol. 1996;13 (Suppl 1):S2–S7. doi: 10.1097/00042560-199600001-00002. [DOI] [PubMed] [Google Scholar]
  25. Murphy E. L., Figueroa J. P., Gibbs W. N., Holding-Cobham M., Cranston B., Malley K., Bodner A. J., Alexander S. S., Blattner W. A. Human T-lymphotropic virus type I (HTLV-I) seroprevalence in Jamaica. I. Demographic determinants. Am J Epidemiol. 1991 Jun 1;133(11):1114–1124. doi: 10.1093/oxfordjournals.aje.a115824. [DOI] [PubMed] [Google Scholar]
  26. Nagai M., Usuku K., Matsumoto W., Kodama D., Takenouchi N., Moritoyo T., Hashiguchi S., Ichinose M., Bangham C. R., Izumo S. Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP. J Neurovirol. 1998 Dec;4(6):586–593. doi: 10.3109/13550289809114225. [DOI] [PubMed] [Google Scholar]
  27. Nakamura N., Arakaki Y., Sunagawa H., Shiohira Y., Uehara H., Miyasato T., Koyama Y., Ogawa Y., Kowatari T. Influence of immunosuppression in HTLV-1-positive renal transplant recipients. Transplant Proc. 1998 Jun;30(4):1324–1326. doi: 10.1016/s0041-1345(98)00261-9. [DOI] [PubMed] [Google Scholar]
  28. Nakane S., Shirabe S., Moriuchi R., Mizokami A., Furuya T., Nishiura Y., Okazaki S., Yoshizuka N., Suzuki Y., Nakamura T. Comparative molecular analysis of HTLV-I proviral DNA in HTLV-I infected members of a family with a discordant HTLV-I-associated myelopathy in monozygotic twins. J Neurovirol. 2000 Aug;6(4):275–283. doi: 10.3109/13550280009030753. [DOI] [PubMed] [Google Scholar]
  29. Niewiesk S., Daenke S., Parker C. E., Taylor G., Weber J., Nightingale S., Bangham C. R. Naturally occurring variants of human T-cell leukemia virus type I Tax protein impair its recognition by cytotoxic T lymphocytes and the transactivation function of Tax. J Virol. 1995 Apr;69(4):2649–2653. doi: 10.1128/jvi.69.4.2649-2653.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Okochi K., Sato H., Hinuma Y. A retrospective study on transmission of adult T cell leukemia virus by blood transfusion: seroconversion in recipients. Vox Sang. 1984;46(5):245–253. doi: 10.1111/j.1423-0410.1984.tb00083.x. [DOI] [PubMed] [Google Scholar]
  31. Osame M., Izumo S., Igata A., Matsumoto M., Matsumoto T., Sonoda S., Tara M., Shibata Y. Blood transfusion and HTLV-I associated myelopathy. Lancet. 1986 Jul 12;2(8498):104–105. doi: 10.1016/s0140-6736(86)91636-3. [DOI] [PubMed] [Google Scholar]
  32. Osame M., Usuku K., Izumo S., Ijichi N., Amitani H., Igata A., Matsumoto M., Tara M. HTLV-I associated myelopathy, a new clinical entity. Lancet. 1986 May 3;1(8488):1031–1032. doi: 10.1016/s0140-6736(86)91298-5. [DOI] [PubMed] [Google Scholar]
  33. Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415–7419. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Reeves W. C., Levine P. H., Cuevas M., Quiroz E., Maloney E., Saxinger W. C. Seroepidemiology of human T cell lymphotropic virus in the Republic of Panama. Am J Trop Med Hyg. 1990 Apr;42(4):374–379. doi: 10.4269/ajtmh.1990.42.374. [DOI] [PubMed] [Google Scholar]
  35. Rosenblum M. K., Brew B. J., Hahn B., Shaw G., Haase A., Maroushek S., Price R. W. Human T-lymphotropic virus type I-associated myelopathy in patients with the acquired immunodeficiency syndrome. Hum Pathol. 1992 May;23(5):513–519. doi: 10.1016/0046-8177(92)90128-p. [DOI] [PubMed] [Google Scholar]
  36. Soriano V., Gutiérrez M., Vallejo A., Aguilera A., Calderón E., Franco E. Infección por HTLV-I en España. Análisis de 24 casos identificados hasta noviembre de 1994. Grupo Español para el Estudio del HTLV-I/II. Med Clin (Barc) 1995 Sep 9;105(7):246–250. [PubMed] [Google Scholar]
  37. Soriano V., Mas A. Riesgo actual de transmisión de retrovirus por transfusiones. Sangre (Barc) 1995 Oct;40(5):407–416. [PubMed] [Google Scholar]
  38. Stuver S. O., Tachibana N., Okayama A., Shioiri S., Tsunetoshi Y., Tsuda K., Mueller N. E. Heterosexual transmission of human T cell leukemia/lymphoma virus type I among married couples in southwestern Japan: an initial report from the Miyazaki Cohort Study. J Infect Dis. 1993 Jan;167(1):57–65. doi: 10.1093/infdis/167.1.57. [DOI] [PubMed] [Google Scholar]
  39. Taylor G. P. Pathogenesis and treatment of HTLV-I associated myelopathy. Sex Transm Infect. 1998 Oct;74(5):316–322. doi: 10.1136/sti.74.5.316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Toro Carlos, Rodés Berta, Aguilera Antonio, Caballero Estrella, Benito Rafael, Tuset Concepción, García Juan, De Lejarazu Raúl Ortiz, Eirós José M., Calderón Enrique. Clinical impact of HTLV-1 infection in Spain: implications for public health and mandatory screening. J Acquir Immune Defic Syndr. 2002 Jul 1;30(3):366–368. doi: 10.1097/00126334-200207010-00016. [DOI] [PubMed] [Google Scholar]
  41. Toro Carlos, Rodés Berta, Poveda Eva, Soriano Vincent. Rapid development of subacute myelopathy in three organ transplant recipients after transmission of human T-cell lymphotropic virus type I from a single donor. Transplantation. 2003 Jan 15;75(1):102–104. doi: 10.1097/00007890-200301150-00019. [DOI] [PubMed] [Google Scholar]
  42. Usuku K., Nishizawa M., Matsuki K., Tokunaga K., Takahashi K., Eiraku N., Suehara M., Juji T., Osame M., Tabira T. Association of a particular amino acid sequence of the HLA-DR beta 1 chain with HTLV-I-associated myelopathy. Eur J Immunol. 1990 Jul;20(7):1603–1606. doi: 10.1002/eji.1830200729. [DOI] [PubMed] [Google Scholar]
  43. Wiktor S. Z., Pate E. J., Rosenberg P. S., Barnett M., Palmer P., Medeiros D., Maloney E. M., Blattner W. A. Mother-to-child transmission of human T-cell lymphotropic virus type I associated with prolonged breast-feeding. J Hum Virol. 1997 Nov-Dec;1(1):37–44. [PubMed] [Google Scholar]
  44. Wiktor S. Z., Piot P., Mann J. M., Nzilambi N., Francis H., Vercauteren G., Blattner W. A., Quinn T. C. Human T cell lymphotropic virus type I (HTLV-I) among female prostitutes in Kinshasa, Zaire. J Infect Dis. 1990 Jun;161(6):1073–1077. doi: 10.1093/infdis/161.6.1073. [DOI] [PubMed] [Google Scholar]
  45. Zarranz J. J., Rouco I., Gómez-Esteban J. C., Corral J. Human T lymphotropic virus type I (HTLV-1) associated myelopathy acquired through a liver transplant. J Neurol Neurosurg Psychiatry. 2001 Dec;71(6):818–818. doi: 10.1136/jnnp.71.6.818. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES