Immunosuppression bei Handtransplantation: State of the Art, Zukunftsperspektiven

Zusammenfassung

Die Minimierung der immunosuppressiven Therapie, stellt eine der größten Herausforderungen auf dem Gebiet der Transplantationsmedizin dar. Das dafür erforderliche Verständnis der molekularen Abläufe ist weiterhin Gegenstand intensiver Forschung. Dieser Review beschreibt den derzeitigen Stand des Wissens über akute Abstoßungsreaktionen von „Composite Tissue” Allotransplantaten und beleuchtet sowohl konventionelle als auch innovative Therapiemöglichkeiten.

Abstract

Avoidance or minimization of maintenance immunosuppression represents the key step for promoting wider applicability of reconstructive transplantation. Understanding the mechanisms of composite tissue allograft rejection is of essence in working towards this goal. We herein review the current knowledge on acute rejection in reconstructive transplantation and discuss findings in the light of novel immunosuppressive and immunomodulatory strategies.

Schlüsselwörter

Transplantationschirurgie - interdisziplinäre plastische Chirurgie - Handchirurgie - obere Extremität - Körperregion und Anatomie - Histologie

Key words

transplantation surgery - hand surgery - upper limb - histology

Literatur

• 1 Petruzzo P, Lanzetta M, Dubernard JM. et al . The international registry on hand and composite tissue transplantation.  Transplantation. 2008;  86 487-492
• 2 Cendales LC, Kanitakis J, Schneeberger S. et al . The Banff 2007 working classification of skin-containing composite tissue allograft pathology.  Am J Transplant. 2008;  8 1396-1400
• 3 Kasiske BL, Snyder JJ, Gilbertson DT. et al . Cancer after kidney transplantation in the United States.  Am J Transplant. 2004;  4 905-913
• 4 Matin RN, Mesher D, Proby CM. et al . Melanoma in organ transplant recipients: clinicopathological features and outcome in 100 cases.  Am J Transplant. 2008;  8 1891-1900
• 5 Birkeland SA, Lokkegaard H, Storm HH. Cancer risk in patients on dialysis and after renal transplantation.  Lancet. 2000;  355 1886-1887
• 6 Luppi M, Barozzi P, Torelli G. Skin cancers after organ transplantation.  N Engl J Med. 2003;  349 612-614 , author reply 612–614
• 7 Harris EC BB. Suicide as an outcome for medical disorders.  Medicine (Baltimore). 1994;  281-296
• 8 Bonatti H BG, Margreiter R, Schneeberger S. Infectious Complications in Three Double Hand Recipients: Experience From a Single Center.  Transplant Proc. 2009;  41 517-520
• 9 Schneeberger S, Lucchina S, Lanzetta M. et al . Cytomegalovirus-related complications in human hand transplantation.  Transplantation. 2005;  80 441-447
• 10 Bonatti H, Lass-Florl C, Zelger B. et al . Alternaria alternata soft tissue infection in a forearm transplant recipient.  Surg Infect (Larchmt). 2007;  8 539-544
• 11 Bonatti H, Aigner F, De Clercq E. et al . Local administration of cidofovir for human papilloma virus associated skin lesions in transplant recipients.  Transpl Int. 2007;  20 238-246
• 12 Brandacher G, Ninkovic M, Piza-Katzer H. et al . The innsbruck hand transplant program: update at 8 years after the first transplant.  Transplant Proc. 2009;  41 491-494
• 13 Cobbold SP. New trends in immunosuppression.  Int Immunopharmacol. 2005;  5 1-5
• 14 Gorantla VS, Barker JH, Jones  Jr. JW. et al . Immunosuppressive agents in transplantation: mechanisms of action and current anti-rejection strategies.  Microsurgery. 2000;  20 420-429
• 15 Bretscher P, Cohn M. A theory of self-nonself discrimination.  Science. 1970;  169 1042-1049
• 16 June CH, Vandenberghe P, Thompson CB. The CD28 and CTLA-4 receptor family.  Chem Immunol. 1994;  59 62-90
• 17 Lechler RI, Batchelor JR. Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells.  J Exp Med. 1982;  155 31-41
• 18 Batchelor JR, Lechler RI. Why MHC incompatible grafts induce strong primary alloimmunity.  Transplant Proc. 1982;  14 535-537
• 19 Haspot F, Villemain F, Laflamme G. et al . Differential effect of CD28 versus B7 blockade on direct pathway of allorecognition and self-restricted responses.  Blood. 2002;  99 2228-2234
• 20 Lechler R, Lombardi G. The structural basis of alloreactivity.  Immunol Res. 1990;  9 135-146
• 21 Benichou G, Takizawa PA, Olson CA. et al . Donor major histocompatibility complex (MHC) peptides are presented by recipient MHC molecules during graft rejection.  J Exp Med. 1992;  175 305-308
• 22 Auchincloss  Jr. H, Lee R, Shea S. et al . The role of “indirect” recognition in initiating rejection of skin grafts from major histocompatibility complex class II-deficient mice.  Proc Natl Acad Sci USA. 1993;  90 3373-3377
• 23 Barnaba V, Watts C, de Boer M. et al . Professional presentation of antigen by activated human T cells.  Eur J Immunol. 1994;  24 71-75
• 24 Mannie MD, Dawkins JG, Walker MR. et al . MHC class II biosynthesis by activated rat CD4+ T cells: development of repression in vitro and modulation by APC-derived signals.  Cell Immunol. 2004;  230 33-43
• 25 Schneeberger S, Gorantla VS, van Riet RP. et al . Atypical acute rejection after hand transplantation.  Am J Transplant. 2008;  8 688-696
• 26 Schneeberger S, Kreczy A, Brandacher G. et al . Steroid- and ATG-resistant rejection after double forearm transplantation responds to Campath-1H.  Am J Transplant. 2004;  4 1372-1374
• 27 Schneeberger S, Ninkovic M, Piza-Katzer H. et al . Status 5 years after bilateral hand transplantation.  Am J Transplant. 2006;  6 834-841
• 28 Schneeberger S, Ninkovic M, Gabl M. et al . First forearm transplantation: outcome at 3 years.  Am J Transplant. 2007;  7 1753-1762
• 29 Kanitakis J, Jullien D, Petruzzo P. et al . Clinicopathologic features of graft rejection of the first human hand allograft.  Transplantation. 2003;  76 688-693
• 30 Wang HJ, Ding YQ, Pei GX. et al . A preliminary pathological study on human allotransplantation.  Chin J Traumatol. 2003;  6 284-287
• 31 Kanitakis J, Jullien D, Nicolas JF. et al . Sequential histological and immunohistochemical study of the skin of the first human hand allograft.  Transplantation. 2000;  69 1380-1385
• 32 Sugita K, Kabashima K, Atarashi K. et al . Innate immunity mediated by epidermal keratinocytes promotes acquired immunity involving Langerhans cells and T cells in the skin.  Clin Exp Immunol. 2007;  147 176-183
• 33 Czernielewski JM, Bagot M. Class II MHC antigen expression by human keratinocytes results from lympho-epidermal interactions and gamma-interferon production.  Clin Exp Immunol. 1986;  66 295-302
• 34 Gaspari AA, Katz SI. Induction and functional characterization of class II MHC (Ia) antigens on murine keratinocytes.  J Immunol. 1988;  140 2956-2963
• 35 Stringer CP, Hicks R, Botham PA. The expression of MHC class II (Ia) antigens on mouse keratinocytes following epicutaneous application of contact sensitizers and irritants.  Br J Dermatol. 1991;  125 521-528
• 36 Uchi H, Terao H, Koga T. et al . Cytokines and chemokines in the epidermis.  J Dermatol Sci. 2000;  24 ((Suppl 1)) S29-S38
• 37 Dubernard JM, Owen E, Herzberg G. et al . Human hand allograft: report on first 6 months.  Lancet. 1999;  353 1315-1320
• 38 Jones TR, Ha J, Williams MA. et al . The role of the IL-2 pathway in costimulation blockade-resistant rejection of allografts.  J Immunol. 2002;  168 1123-1130
• 39 Niemeyer G, Koch M, Light S. et al . Long-term safety, tolerability and efficacy of daclizumab (Zenapax) in a two-dose regimen in liver transplant recipients.  Am J Transplant. 2002;  2 454-460
• 40 Schneeberger S, Landin L, Kaufmann C. et al . Alemtuzumab: key for minimization of maintenance immunosuppression in reconstructive transplantation?.  Transplant Proc. 2009;  41 499-502
• 41 Cendales L, Hardy MA. Immunologic considerations in composite tissue transplantation: overview.  Microsurgery. 2000;  20 412-419
• 42 Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms.  Clin Sci (Lond). 1998;  94 557-572
• 43 Allison AC, Eugui EM. Immunosuppressive and other effects of mycophenolic acid and an ester prodrug, mycophenolate mofetil.  Immunol Rev. 1993;  136 5-28
• 44 Mathew TH. A blinded, long-term, randomized multicenter study of mycophenolate mofetil in cadaveric renal transplantation: results at three years. Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group.  Transplantation. 1998;  65 1450-1454
• 45 Liu J, Farmer  Jr. JD, Lane WS. et al . Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes.  Cell. 1991;  66 807-815
• 46 Kahan BD, Podbielski J, Napoli KL. et al . Immunosuppressive effects and safety of a sirolimus/cyclosporine combination regimen for renal transplantation.  Transplantation. 1998;  66 1040-1046
• 47 Sehgal SN. Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression.  Clin Biochem. 1998;  31 335-340
• 48 Lanzetta M, Petruzzo P, Dubernard JM. et al . Second report (1998-2006) of the International Registry of Hand and Composite Tissue Transplantation.  Transpl Immunol. 2007;  18 1-6
• 49 Jones JW, Gruber SA, Barker JH. et al . Successful hand transplantation. One-year follow-up. Louisville Hand Transplant Team.  N Engl J Med. 2000;  343 468-473
• 50 Schuind F, Van Holder C, Mouraux D. et al . The first Belgian hand transplantation – 37 month term results.  J Hand Surg [Br]. 2006;  31 371-376
• 51 Petruzzo P, Badet L, Gazarian A. et al . Bilateral hand transplantation: six years after the first case.  Am J Transplant. 2006;  6 1718-1724
• 52 Schneeberger S, Gorantla VS, Hautz T. et al . Immunosuppression and rejection in human hand transplantation.  Transplant Proc. 2009;  41 472-475
• 53 Dubernard JM, Lengele B, Morelon E. et al . Outcomes 18 months after the first human partial face transplantation.  N Engl J Med. 2007;  357 2451-2460
• 54 Starzl TE. Immunosuppressive therapy and tolerance of organ allografts.  N Engl J Med. 2008;  358 407-411
• 55 Kawai T CA, Spitzer TR, Tolkoff-Rubin N. et al . HLA-mismatched renal transplantation without maintenance immunosuppression.  N Engl J Med. 2008;  385 353-361

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