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Antibodies against retroviral core proteins in relation to disease outcome in patients with mycosis fungoides

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Summary

We have studied the relationship of antibodies reacting with human retroviral core proteins to the disease outcome in Finnish mycosis fungoides (MF) patients in a prospective manner. Antibodies recognizing human T-cell leukaemia/lymphoma virus I (HTLV-I) or human immunodeficiency virus type 1 (HIV-1) core proteins were found in 12 of 14 MF patients as shown by the Western blot method. The antibody reactivities showed three patterns: three patients had antibodies cross-reacting with the gag-encoded core proteins of both HTLV-I and HIV-1; seven patients showed antibodies reacting with HTLV-I core proteins only; and the sera of two patients reacted with HIV p24 core protein only. When following the clinical course of these patients, we found that the three patients with antibodies cross-reacting with both viruses had the most fulminant clinical course, and the overall duration of MF was, on average, 4 years less than in the rest of the patients. None of the patients, however, became leukaemic, or showed any other features suggestive of acute T-cell leukaemia/lymphoma (ATL). Two patients, who did not show anti-retroviral antibodies during the follow-up, had a stable disease with plaque-type skin lesions. Histological or immunohistological typing of the skin infiltrates did not correlate with the disease outcome or the above antibody patterns. Our results thus raise the possibility that an unknown retrovirus, immunologically related to the known human retroviruses, may be aetiologically linked to MF.

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References

  1. Abrams MB, Sidawy M, Novich M (1985) Smoldering HTLV-associated T-cell leukemia. Arch Intern Med 145:2257–2259

    Google Scholar 

  2. Albert J, Bredberg U, Chiodi F, Böttiger B, Fenyö E, Norrby E, Biberfeld G (1987) A new human retrovirus isolate of West African origin (SBL-6669) and its relationship to HTLV-IV, LAV-II and HTLV-IIIB. AIDS Res Hum Retroviruses 3:3–10

    Google Scholar 

  3. Blomberg J, FÄldt R (1985) Antibodies to human adult T cell leukaemia virus type I associated antigens in Swedish leukaemia patients and blood donors. Br J Haematol 60:555–557

    Google Scholar 

  4. Bunn PA, Lamberg SI (1979) Report of the committee on staging and classification of cutaneous T-cell lymphomas. Cancer Treat Rev 63:725

    Google Scholar 

  5. Clavel F, Guetard D, Brun-Vezinet F, Chamaret S, Rey M-A, Santos-Ferreira M, Laurent AG, Dauguet C, Katlama C, Rouzioux C, Klatzmann D, Champalimaud J, Montagnier L (1986) Isolation of a new human retrovirus from West African patients with AIDS. Science 233:343–346

    Google Scholar 

  6. Dmitrovsky E, Matthews MJ, Bunn PA, Schechter G, Makuch R, Winkler C, Etty J, Sausville E, Ihde D (1987) Cytologic transformation in cutaneous T-cell lymphoma: a clinicopathologic entity associated with poor prognosis. J Clin Oncol 5:208–215

    Google Scholar 

  7. Franchini G, Wong-Staal F, Gallo RC (1984) Human T-cell leukemia virus HTLV-I transcripts in fresh and cultured cells of patients with acute T-cell leukemia. Proc Natl Acad Sci USA 81:6207–6211

    Google Scholar 

  8. Gazzolo L, DucDodon M (1987) Direct activation of resting T lymphocytes by human T-lymphotropic virus type I. Nature 326:714–717

    Google Scholar 

  9. Gessain A, Barin F, Vernant JC, Gout O, Maurs L, Calender A, Thé G de (1985) Antibodies to human T-lymphotropic virus type I in patients with tropical spastic paraparesis. Lancet II:407–410

    Google Scholar 

  10. Hanaoka M, Sasaki M, Matsumoto H (1979) Adult T-cell leukemia. Histological classifictaion and characteristics. Acta Pathol Jpn 29:723–738

    Google Scholar 

  11. Haseltine WA (1988) Replication and pathogenesis of the AIDS virus. J AIDS 1:217–240

    Google Scholar 

  12. Hinuma Y, Komoda H, Chosa T, Kondo T, Kohakura M, Takenaka T, Kikuchi M, Ichimaru M, Yonoki K, Sato I, Matsuo R, Takiuchi Y, Uchino H, Hanaoka M (1982) Antibodies to adult T-cell leukemia-virus-associated antigen (ATLA) in sera from patients with ATL and controls in Japan: a nationwide seroepidemiologic study. Int J Cancer 29:631–635

    Google Scholar 

  13. Hoppe RT, Cox RS, Fuks Z, Price N, Bagshaw M, Farber E (1979) Electron-beam therapy for mycosis fungoides: the Stanford experience. Cancer Treat Rep 63:691–700

    Google Scholar 

  14. Jacobson S, Raine CS, Mingioli ES, McFarlin DE (1988) Isolation of an HTLV-I-like retrovirus from patients with tropical spastic paraparesis. Nature 331:540–543

    Google Scholar 

  15. Jaffe ES, Cosman J, Blattner WA, Robert-Guroff M, Blayney D, Gallo RC, Bunn P (1984) The pathologic spectrum of adult T-cell leukemia/lymphoma in the United States. Am J Surg Pathol 8:263–275

    Google Scholar 

  16. Jeang K-T, Boros I, Brady J, Kadonovich M, Khoury G (1988) Characterization of cellular factors that interact with the human T-cell leukemia virus type I p40x-responsive 21-base-pair sequence. J Virol 62:4499–4509

    Google Scholar 

  17. Kaltoft K, Thestrup-Pedersen K, Jensen JR, Bisballe S, Zachariae H (1984) Establishment of T and B cell lines from patients with mycosis fungoides. Br J Dermatol 111:303–308

    Google Scholar 

  18. Kaltoft K, Bisballe S, Rasmussen HF, Thestrup-Pedersen K, Boehncke W-H, Völker H, Sterry W (1988) C-type particles are inducible in Se-Ax, a continuous T-cell line from a patient with Sezary's syndrome. Arch Dermatol Res 280:264–267

    Google Scholar 

  19. Kaplanski S, Wong-Staal F, Farnarier-Scidel C, DucDodon M, Golstein M-M, Jancovici E, Sayag J, Gazzolo L, Depieds R (1986) Detection of HTLV-I (Human T-cell lymphotropic virus, type 1) proviral DNA in leukemic cells from a French patient with Sezary syndrome. Leuk Res 10:375–380

    Google Scholar 

  20. Koprowski H, DeFreitas E, Harper M, Sandberg-Wollheim M, Sheremata W, Robert-Guroff M, Saxinger C, Feinberg M, Wong-Staal F, Gallo RC (1985) Multiple sclerosis and human T-cell lymphotropic retroviruses. Nature 318:154–160

    Google Scholar 

  21. Lambert WC (1985) Premycotic eruptions. Dermatol Clin 3:629–645

    Google Scholar 

  22. Lange Wantzin G, Thomsen K, Nissen NI, Saxinger C, Gallo R (1986) Occurrence of human T cell lymphotropic virus (type I) antibodies in cutaneous T cell lymphoam. J Am Acad Dermatol 15:598–602

    Google Scholar 

  23. Lazar AP, Caro W, Roenigk H, Pinski K (198) Parapsoriasis and mycosis fungoides: the Northwestern University experience, 1970 to 1985. J Am Acad Dermatol 21:919–923

  24. Lever WF, Schaumburg-Lever G (1983) Histopathology of the skin, 6th edn. Lippincott, Philadelphia

    Google Scholar 

  25. Lusso P, Ensoli B, Markham PD, Ablashi D, Salahuddin SZ, Tschachler E, Wong-Staal F, Gallo RC (1989) Productive dual infection of human CD4+ T lymphocytes by HIV-1 and HHV-6. Nature 337:370–373

    Google Scholar 

  26. Maeda K, Takahashi M (1989) Characterization of skin infiltrating cells in adult T-cell leukaemia/lymphoma (ATLL): clinical, histological and immunhistochemical studies on eight cases. Br J Dermatol 121:603–612

    Google Scholar 

  27. Malim MH, Hauber J, Fenrick R, Cullen BR (1988) Immunodeficiency virus REV transactivator modulates the expression of viral regulatory genes. Nature 335:181–813

    Google Scholar 

  28. Manzari V, Grailone A, Barillari G, Zani M, Collati E, Pandolfi F, Rossi G de, Liso V, Babbo P, Robert-Guroff M, Frat I (1985) HTLV-I is endemic in Southern Italy: detection of the first infectious cluster in a white population. Int J Cancer 36:557–559

    Google Scholar 

  29. Manzari V, Gismondi A, Barillari G, Morrone S, Modesti A, Albonici L, DeMarchis L, Fazio U, Gradilone A, Zani M, Frati L, Santoni A (1987) HTLV-V: a new human retrovirus isolated in a Tac-negative T cell lymphoma/leukemia. Science 238:1581

    Google Scholar 

  30. Nieminen P, Saksela E (1984) A shared antigenic specificity of human large granular lymphocytes and precursors of NK-like and allospecific cytotoxic effector cells. J Immunol 133:702

    Google Scholar 

  31. Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, Igata A, Matsumoto M, Tara M (1986) HTLV-I associated myelopathy, a new clinical entity. Lancet 1:1031–1032

    Google Scholar 

  32. Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC (1980) 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 USA 77:7415–7419

    Google Scholar 

  33. Poiez B, Ruscetti F, Reitz M, Kalyanaraman V, Gallo RC (1981) Isolation of a new type-C retrovirus (HTLV) in primary uncultured cells of a patient with Sezary T-cell leukemia. Nature 294:268–271

    Google Scholar 

  34. Popovic M, Sarin PS, Robert-Guroff M, Kalyanaraman V, Mann D, Minowada J, Gallo RC (1983) Isolation and transmission of human retrovirus (human T-cell leukemia virus). Science 219:856–859

    Google Scholar 

  35. Popovic M, Sarngadharan MG, Read E, Gallo RC (1984) Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 224:497–500

    Google Scholar 

  36. Ralfkiaer E, O'Connor NTJ, Crick JA, Wantzin GL, Mason D (1987) Genotypic analysis of cutaneous T-cell lymphomas. J Invest Dermatol 88:762–765

    Google Scholar 

  37. Ranki A, Krohn K (1987) Cross-reacting antibodies to gag proteins of HTLV-I and HTLV-III in patients with mycosis fungoides or its prodrome large-plaque parapsoriasis. In:Gallo RC, Haseltine W, Klein G, Hausen H zur (eds) Viruses and human cancer. Liss, New York, pp 43–57

    Google Scholar 

  38. Ranki A, Kianto U, Kanerva L, Tolvanen E, Johansson E (1984) Immunohistochemical and electron microscopic characterization of the cellular infiltrate in alopecia. J Invest Dermatol 83:7–11

    Google Scholar 

  39. Ranki A, Valle S-L, Krohn M, Antonen J, Allain J-P, Leuther M, Franchini G, Krohn K (1987) Long latency precedes overt seroconversion in sexually transmitted HIV infection. Lancet II:589–593

    Google Scholar 

  40. Ranki A, Weiss SH, Valle S-LAntonen J, Krohn K (1987) Neutralizing antibodies in HIV (HTLV-III) infection: correlation with clinical outcome and with antibody response against different viral proteins. Clin Exp Immunol 69:231–239

    Google Scholar 

  41. Ranki A, Johansson E, Krohn K (1988) Interpretation of antibodies reactin solely with human retroviral core proteins. N Engl J Med 318:448–449

    Google Scholar 

  42. Ranki A, Zheng Y, Kirjarinta M, Karvonen J, Saxinger C, Ashorn P, Safai B, Krohn K (1989) No evidence for true HTLV-I or HIV-1 antibodies in Finnish Lapps. AIDS Res Hum Retroviruses 5:321–326

    Google Scholar 

  43. Reddy PE, Sandberg-Wollheim M, Mettus RV, Ray PE, DeFreitas E, Koprowski H (1989) Amplification and molecular cloning of HTLV-I sequence from DNA of multiple sclerosis patients. Science 243:529–533

    Google Scholar 

  44. Rinne E, Förström L, Lassus A (1989) Interferon alpha-2a in the treatment of six patients of cutaneous T-cell lymphoma. [A] Int. Dermatology Symposium on Interferons and Related Lymphokines, Berlin, FRG, J Invest Dermatol 93:572

    Google Scholar 

  45. Saxinger CW, Lange Wantzin G, Thomsen K, Hoh M, Gallo RC (1985) Occurrence of HTLV-I antibodies in Danish patients with cutaneous T cell lymphoma. Scand J Haematol 34:455–462

    Google Scholar 

  46. Sezary A (1949) Une nouvelle reticulose cutanée. La reticulose migne leucemique a histomonocytes monstreux et a forme d'érythrodermie oedemateuse et pigmentée. Ann Dermatol Syphillgr 9:5

    Google Scholar 

  47. Siekevitz M, Josephs S, Dukovich M, Peffer N, Wong-Staal F, Greene W (1987) Activation of the HIV-1 LTR by T cell mitogens and the trans-activator protein of HTLV-I. Science 238:1575–1578

    Google Scholar 

  48. Tajima K, Kamura S, Ito S (1987) Epidemiological features of HTLV-I carriers and incidence of ATL and ATL-endemic island: a report of the community-based co-operative study in Tsushima, Japan. Int J Cancer 40:741–746

    Google Scholar 

  49. Tamura K, Nagamine N, Araki Y, Seta M, Okayama A, Kawano K, Tachihana N, Tsuda K, Kuroki Y, Narita H, Inoue S, Suzumiya J, Sumiyoshi A, Aratake Y, Ohtaki S, Torigoe J, Kawachi J (1986) Clinical analysis of 33 patients with adult T-cell leukemia (ATL)-diagnostic criteria and significance of high-and low-risk ATL. Int J Cancer 37:335–341

    Google Scholar 

  50. Tong-Starksen SE, Luciw P, Peterlin BM (1987) Human immunodeficiency virus long terminal repeat responds to T-cell activation signals. Proc Natl Acad Sci USA 84:6845–6849

    Google Scholar 

  51. Turbitt M, MacKie R (1985) p19 Antigen in skin and lymph nodes of patient with advanced mycosis fungoides. Lancet II:945

    Google Scholar 

  52. Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H (1977) Adult T-cell leukemia: clinical and hematological features of 16 cases. Blood 50:481–491

    Google Scholar 

  53. Van der Loo EM, Van Muljen WA, Van Vloten Beens W, Scheffer E, Meijer C (1979) C-type virus-like particles specifically localized in Langerhans cells and related cells of skin and lymph nodes with mycosis fungoides and Sezar'y syndrome. A morphological and biochemical study. Virchows Arch [Cell Pathol] 31:193–203

    Google Scholar 

  54. Helm D von der, Helm K von der, Burg G (1988) Antikörper gegen HTLV-I by T-lymphoproliferativen Erkrankungen der Haut. Hautarzt 39:348–350

    Google Scholar 

  55. Weiss LM, Hu E, Wood GS, Moulds C, Cleary M, Warnke R, Sklar J (1985) Clonal rearrangements of T-cell receptor genes in mycosis fungoides and dermatopathic lymphadenopathy. N Engl J Med 313:539–544

    Google Scholar 

  56. Wong-Staal F, Gallo RC (1985) Human T-lymphotropic retroviruses. Nature 317:395–403

    Google Scholar 

  57. Yamaguchi K, Nishumura H, Kohrogi A, Jono M, Miyamoto Y, Takatsuki K (1983) A proposal for smoldering adult T-cell leukemia: clinicopathologic study of five cases. Blood 62:758–766

    Google Scholar 

  58. Yoshida M (1987) Expression of the HTLV-I genome and its association with a unique T-cell malignancy. Biochim Biophys Acta 907:145–161

    Google Scholar 

  59. Yoshida M, Seiki M, Yamaguchi K, Takatsuki K (1984) Monoclonal integration of human T-cell leukemia provirus in all primary tumors of adult T-cell leukemia suggest causative role of human T-cell leukemia virus in the disease. Proc Natl Acad Sci USA 81:2534–2537

    Google Scholar 

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Ranki, A., Niemi, K.M., Nieminen, P. et al. Antibodies against retroviral core proteins in relation to disease outcome in patients with mycosis fungoides. Arch Dermatol Res 282, 532–538 (1990). https://doi.org/10.1007/BF00371949

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