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Immunohistological skin alterations in allogeneic bone marrow transplantation

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Summary

Skin biopsies of 26 patients with leukemia and seven patients with aplastic anemia were investigated before and at different stages after allogeneic bone marrow transplantation (BMT) to establish the immunological criteria which distinguish skin alterations during normal reconstitution from dermal lesions mediated by graft-versushost disease (GvHD). Of the 33 patients studied 27 presented with clinically diagnosed acute and/or chronic GvHD, one patient died of bone marrow rejection. Immunohistological analysis of the respective skin biopsies with selected monoclonal antibodies against human leukocyte antigens (HLA) and differentiation antigens of the lympho-hematopoietic cells revealed low dermal mononuclear cell counts with phenotypically normal constituents in five cases with uncomplicated reconstitution post-grafting. In contrast, increased dermal cellular infiltrates predominantly consisting of Lyt 3+, OKT 8+ T-lymphocytes, as well as of a large number of Ia-like (immune response associated = HLA-D) determinant+ monocytes/macrophages were observed in all patients with active acute/chronic GvH reactivity. As sign of activation simultaneous expression of HLA-D region products was also found on a subset of the invading OKT 8+ T-lymphocytes. Progression of GvHD was associated with additional surface staining of keratinocytes for Ia-like determinants. Loss of Ia-like determinant+, OKT 6+ dentritic epithelial cells in all leukemic patients, as well as in patients with aplastic anemia with or without GvHD suggested damage of Langerhans cells due to the previous radiotherapy and/or specific immunological destruction. In patients with fatal outcome of GvHD prolonged reduction of these dentritic epithelial cells seemed to be indicative of impaired immune reconstitution or bone marrow dysfunction. Thus immunopathological features of skin GvHR may enable early recognition and prognostic evaluation of this disease possibly allowing more effective therapy.

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Abbreviations

GvHD:

graft-versus-host disease

GvHR:

graft-versus-host reactivity

SAA:

severe aplastic anemia

TBI:

total body irradiation

BMT:

bone marrow transplantation

HLA:

human leukocyte antigens

Ia-like antigens:

Immune-response-associated antigens

PBS:

phosphate buffered saline

FITC:

fluorescein isothiocyanate

TRITC:

tetramethylrhodamine isothiocyanate

References

  • Abo T, Balch CM (1981) A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol 127:1024–1029

    Google Scholar 

  • Abramson CS, Kersey JH, LeBien TW (1981) A monoclonal antibody (BA-1) reactive with cells of human B-lymphocyte lineage. J Immunol 126:83–88

    Google Scholar 

  • Barnstable CJ, Bodmer WF, Brown G, Galfrè G, Milstein C, Williams AF, Ziegler A (1978) Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens — new tools for genetic analysis. Cell 14:9–20

    Google Scholar 

  • De Bruin HG, Astaldi A, Leupers T, van de Griend R, Dooren LJ, Schnellekens PTA, Tanke HJ, Roos M, Voosen JM (1981) T lymphocyte characteristics in bone marrow transplanted patients. II. Analysis with monoclonal antibodies. J Immunol 127:244–251

    Google Scholar 

  • Glazier A, Tutschka PJ, Farner ER, Santos GW (1983) Graftversus-host disease in Cyclosporin-A-treated rats after syngeneic and autologous bone marrow reconstitution. J Exp Med 158:1–8

    Google Scholar 

  • Gluckman E, Divergie A, Sohier J, Saurat JH (1980) Graftversus-host disease in recipients of syngeneic bone marrow. Lancet I:253–254

    Google Scholar 

  • Gomes MA, Schmitt DS, Souteyrand P, Ohrt C, Brochier J, Thivolet J (1982) Lichen planus and chronic graft-versushost reaction. In situ identification of immunocompetent cell phenotypes. J Cutan Pathol 9:249–257

    Google Scholar 

  • Janossy G, Montano L, Selby WS, Duke O, Panayi G, Lampert J, Thomas JA, Granger S, Bofill M, Tidman N, Thomas HL (1982) T cell subset abnormalities in tissue lesions developing during autoimmune disorders, viral infection and graft-versus-host disease. J Clin Immunol 2:42–56

    Google Scholar 

  • Kamoun M, Martin PJ, Hansen JA, Brown MA, Siadak AW, Nowinski RC (1981) Identification of a human T-lymphocyte surface protein associated with the E-rosette receptor. J Exp Med 153:207–212

    Google Scholar 

  • Krüger GRF, Berard CW, De Lellis RA, Graw RG, Yankee RA, Leventhal BG, Rongentine GN, Herzig GP, Halterman RH, Henderson ES (1971) Graft versus host disease: Morphologic variation and differential diagnosis in 8 cases of HL-A matched bone marrow transplantation. Am J Pathol 63:179–202

    Google Scholar 

  • Kung PC, Goldstein G, Reinherz EL, Schlossman SF (1979) Monoclonal antibodies defining distinctive human T cell surface antigens. Science 206:347–349

    Google Scholar 

  • Lampert JA, Janossy G, Suitters AJ, Bofill M, Palmer S, Gordon-Smith E, Prentice HG, Thomas JA (1982) Immunological analysis of the skin in graft-versus-host disease. Clin Exp Immunol 50:123–131

    Google Scholar 

  • Lerner KG, Kao GF, Storb R, Buckner CD, Clift RA, Thomas ED (1974) Histopathology of graft-versus-host reaction (GVHR) in human recipients of marrow from HLA-matched sibling donors. Transplant Proc 6:367–371

    Google Scholar 

  • Morhenn VA, Abel EA, Marle G (1982) Expression of HLA-DR antigen in skin from patients with psoriasis. J Invest Dermatol 78:165–168

    Google Scholar 

  • Müller C, Schüch K, Pawelec G, Wilms K, Wernet P (1982) Immunohistology of graft-versus-host disease mediated skin lesions and its correlation to a large granular lymphocyte surface phenotype and function. Blut 467:1–6

    Google Scholar 

  • Natali PG, De Martinoc, Quaranta V (1981) Expression of Ia-like antigens in normal human non-lymphoid tissues. Transplantation 31:75–78

    Google Scholar 

  • Parkman R, Rappaport J, Rosen FS, Reinherz EL (1979) Graft-versus-host disease. N Engl J Med 301:556

    Google Scholar 

  • Pawelec G, Shaw S, Ziegler A, Müller C, Wernet P (1982) Differential inhibition of HLA-D or SB-directed secondary lymphoproliferative responses with monoclonal antibodies detecting human Ia-like determinants. J Immunol 129:1070–1075

    Google Scholar 

  • Pober JS, Gimbrone MA, Cotran RS, Reiss CS, Burakoff SJ, Fiess W, Ault KH (1983) Ia expression by vascular endothelium is inducible by activated T cells and by human γ-Interferon. J Exp Med 157:1339–1353

    Google Scholar 

  • Reinherz EL, Kung PC, Goldstein G, Levey RH, Schlossman SF (1980a) Discrete stages of human intrathymic differentiation: Analysis of normal thymocytes and leukemic lymphoblasts of T lineage. Proc Natl Acad Sci (USA) 77:1588–1592

    Google Scholar 

  • Reinherz EL, Kung PC, Goldstein G, Schlossman SF (1980b) A monoclonal antibody reactive with the human cytotoxic/suppressor T cell subset previously defined by heteroantiserum termed TH2. J Immunol 124:1301–1307

    Google Scholar 

  • Sale GE, Lerner KG, Barker EA, Shulman HM, Thomas ED (1977) The skin biopsy in the diagnosis of acute graft-versus-host disease in man. Am J Pathol 89:621–636

    Google Scholar 

  • Saurat JH (1981) Cutaneous manifestations of graft-versus-host disease. Int J Dermatol 20:249–256

    Google Scholar 

  • Shulman HM, Sale GE, Lerner KG, Barker EA, Weiden PL, Sullivan K, Galluci B, Thomas ED, Storb R (1978) Chronic cutaneous graft-versus-host disease in man. Am J Pathol 91:545–570

    Google Scholar 

  • Slavin RE, Santos GW (1973) The graft-versus-host reaction in man after bone marrow transplantation: Pathology, pathogenesis, clinical features and implications. Clin Immunol Immunopathol 1:472–498

    Google Scholar 

  • Stein H, Toksdorf G, Lennert K, Rodt H, Gerdes J (1981) Immunohistologic analysis of the organisation of normal lymphoid tissue and Non-Hodgkin's lymphomas. J Histochem Cytochem 28:746–760

    Google Scholar 

  • Stingl G, Gazza-Stingl LA, Aberer W, Wolff K (1981) Antigen presentation by murine epidermal Langerhans cells and its alteration by ultraviolet B. I Immunol 127:1707–1713

    Google Scholar 

  • Thomas ED, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE, Lerner KG, Glucksberg H, Buckner CD (1975) Bone marrow transplantation. N Engl J Med 292:832–943

    Google Scholar 

  • Tjernlund U (1978) Epidermal expression of HLA-DR antigens in mycosis fungoides. Arch Dermatol Res 268:81–86

    Google Scholar 

  • Tjernlund U (1980) Ia-like antigens in lichen planus. Acta Derm Venereol 60:309–314

    Google Scholar 

  • Uchànska-Ziegler B, Wernet P, Ziegler A (1981) Monoclonal antibodies against human lymphoid and myeloid antigens. AMML cells as immunogen. In: Knapp W (ed) Proceedings of leukemia marker conference. Academic Press, London, pp 243–246

    Google Scholar 

  • Wilms K, Link H, Meyer P, Ostendorf P, Schüch K, Waller HD, Wernet P, Niethammer D, Dopfer H, Schneider W, Schunter F, Breitling G, Frommhold W, Seeger G, Voss AC (1982) Knochemarktransplantation bei Patienten mit Leukämien. Klin Wochenschr 60:1279–1287

    Google Scholar 

  • Wood GS, Warner NL, Warnke RA (1983) Anti-Leu3/T4antibodies react with cells of monocyte-macrophage and Langerhans lineage. J Immunol 131:212–216

    Google Scholar 

  • Ziegler A, Milstein C (1979) A small polypeptide different from β2-microglobulin associated with a human cell surface antigen. Nature 279:243–244

    Google Scholar 

Download references

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Authors and Affiliations

  1. Medizinische Klinik Abt. II Universität Tübingen, Germany

    C. Müller, P. Ostendorf, P. Wernet, K. Schüch, H. Wahl & H. D. Waller

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  1. C. Müller
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  2. P. Ostendorf
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  3. P. Wernet
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  4. K. Schüch
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  5. H. Wahl
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  6. H. D. Waller
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Additional information

Dedicated to Prof. Dr. Dr. h.c. H.E. Bock on the occasion of his 80th birthday

Supported by DFG Sonderforschungsbereich 120, Projekt A 2 and B 1

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Müller, C., Ostendorf, P., Wernet, P. et al. Immunohistological skin alterations in allogeneic bone marrow transplantation. Klin Wochenschr 62, 675–688 (1984). https://doi.org/10.1007/BF01716464

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  • DOI: https://doi.org/10.1007/BF01716464

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