Vai ai contenuti. | Spostati sulla navigazione | Spostati sulla ricerca | Vai al menu | Contatti | Accessibilità

| Crea un account

Germani, Giacomo (2013) Predicting acute cellular rejection after liver transplantation: form liver function test to immune monitoring. [Tesi di dottorato]

Full text disponibile come:

[img]
Anteprima
Documento PDF
3010Kb

Abstract (inglese)

In recent years, the main end point of immunosuppressive therapy after liver transplantation has moved from the prevention of acute cellular rejection (ACR) toward the preservation of long-term graft function and prevention of immunosuppression-related side effects. This approach requires an optimal management of immunosuppressive therapy according to patient risk factors. However, the concentration of immunosuppressive drugs in the serum of patients, which is generally used as a surrogate for the level of immunosuppression, does not provide information about the magnitude of suppression of the immune system. Therefore a reliable marker for the development of ACR, or to predict patients who could tolerate reduced immunosuppression, would be crucial for improving post-transplant management of liver transplanted patients.
The aims of the studies presented in this thesis were: 1) to assess the incidence of ACR after liver transplantation, to identify potential risk factors for ACR, and to evaluate the impact of ACR and its histological severity on outcomes; 2) to evaluate the role of liver function tests and blood eosinophil count as potential biomarkers for ACR after liver transplantation, with special attention on prediction
of histologically proven moderate and severe ACR; 3) to evaluate the expression of specific immunological markers for ACR in patients before and after liver transplantation.
The results of the studies showed that patient and graft survival at 1, 5 and 10 years after liver transplantation were not different with respect to presence or absence of ACR. Only untreated moderate/severe ACR was associated with increased death/graft loss using adjusted Cox regression analysis, whereas mild ACR, whether treated or not, had no effect. With regards to the evaluation of potential markers of ACR, despite peripheral eosinophilia was not sufficiently predictive of moderate/severe ACR, the delta in eosinophil count between the first and second biopsies was the only independent predictor of histological improvement, irrespective of whether bolus steroids were used.
Lastly, we demonstrated that the increased expression of C28 and C38 on both CD4+ and CD8+ T cells and the increased levels of IL-17. These alterations of immune system could be used routinely in clinical practice to assess the immune status of liver transplanted patients and to properly manage immunosuppressive therapy

Abstract (italiano)

Lo scopo principale della terapia immunosoppressiva dopo trapianto di fegato è passato dalla prevenzione del rigetto acuto alla preservazione della funzionalità a lungo termine dell’organo trapiantato e alla prevenzione degli effetti collaterali dovuti alla terapia immunosoppressiva. Per perseguire tale scopo è necessaria una gestione ottimale della terapia immunosoppresiva stessa. Tuttavia, la misurazione dei livelli ematici dei farmaci immunosoppressori, generalmente utilizzati come surrogato dei livelli di immunosoppressione, non fornisce informazioni relative alla reale intensità della soppressione del sistema immunitario. Pertanto l’individuazione di marcatori biologici di rigetto acuto e/o di tolleranza risulta fondamentale per poter migliorare la gestione della terapia immunosoppressiva dopo-trapianto di fegato.
Gli scopi degli studi riportati in questa tesi sono: 1) determinare l’incidenza e gli eventuali fattori di rischio di rigetto acuto dopo trapianto di fegato, valutare in che l’influenza del rigetto acuto e della sua severità istologica sulla sopravvivenza dell’organo e del paziente dopo trapianto di fegato; 2) valutare il ruolo degli indici di funzionalità epatica e della conta eosinofilica ematica come potenziali marcatori biologici di rigetto acuto dopo trapianto di fegato, in particolare di grado moderato/severo; 3) valutare, prima e dopo trapianto di fegato l’espressione di
specifici marcatori immunologici di rigetto acuto.
I risultati degli studi condotti hanno evidenziato come pazienti con diagnosi di rigetto acuto alla biopsia di protocollo presentino una sopravvivenza di organo e paziente, a 1, 5 e 10 anni dal trapianto di fegato, del tutto sovrapponibile a quella di pazienti senza evidenza istologica di rigetto acuto alla biopsia di protocollo. L’insorgenza di rigetto acuto di grado moderato/severo non sottoposto a trattamento farmacologico è tuttavia associata ad aumentata incidenza di decesso o perdita dell’organo post-trapianto.
Nel valutare potenziali marcatori biologici di rigetto acuto, abbiamo dimostrato che nonostante la conta eosinofilica periferica non sia sufficientemente predittiva per lo sviluppo di rigetto acuto post-trapianto, la differenza nella conta eosinofilica tra la prima e la seconda biopsia epatica può essere considerato un fattore predittivo di miglioramento istologico, indipendentemente dall’utilizzo o meno di terapia con boli steroidei. Non è stata invece evidenziata alcuna associazione tra l’alterazione degli indici di funzionalità epatica e l’insorgenza di rigetto acuto.
Infine, è stato dimostrato che l’insorgenza di rigetto acuto risulta associata ad aumentata espressione di CD28 e CD38 sia sui linfociti T CD4+ che CD8+ e ad un aumento dei livelli di IL-17. Tali alterazioni del sistema immunitario potrebbero essere utilizzate nella pratica clinica per valutare lo stato di soppressione del sistema immunitario in pazienti sottoposti a trapianto di fegato con il fine ultimo di una gestione ottimale e personalizzata della terapia immunooppressiva

Statistiche Download - Aggiungi a RefWorks
Tipo di EPrint:Tesi di dottorato
Relatore:Burra, Patrizia - Burroughs, Andrew K.
Dottorato (corsi e scuole):Ciclo 25 > Scuole 25 > BIOLOGIA E MEDICINA DELLA RIGENERAZIONE > SCIENZE EPATOLOGICHE E GASTROENTEROLOGICHE
Data di deposito della tesi:24 Gennaio 2013
Anno di Pubblicazione:24 Gennaio 2013
Parole chiave (italiano / inglese):Rigetto acuto / Acute rejection Trapianto di fegato / Liver Transplantation Marcatori biologici / Biomarkers+ Monitoraggio immunologico / Biomarkers
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/12 Gastroenterologia
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze del Farmaco
Codice ID:5474
Depositato il:16 Ott 2013 08:32
Simple Metadata
Full Metadata
EndNote Format

Bibliografia

I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

1] Terminology for hepatic allograft rejection. International Working Party. Hepatology 1995;22:648-654. Cerca con Google

[2] Hubscher, S. Diagnosis and grading of liver allograft rejection: a European perspective. Transplant Proc 1996;28:504-507. Cerca con Google

[3] Demetris, A.J., S. Lasky, D.H. Van Thiel, T.E. Starzl, and A. Dekker Pathology of hepatic transplantation: A review of 62 adult allograft recipients immunosuppressed with a cyclosporine/steroid regimen. Am J Pathol 1985;118:151-161. Cerca con Google

[4] Porter, K.A. Pathology of liver transplantation. Transplant Rev 1969;2:129-170. Cerca con Google

[5] Snover, D.C., R.K. Sibley, D.K. Freese, H.L. Sharp, J.R. Bloomer, J.S. Najarian, et al. Orthotopic liver transplantation: a pathological study of 63 serial liver biopsies from 17 patients with special reference to the diagnostic features and natural history of rejection. Hepatology 1984;4:1212-1222. Cerca con Google

[6] Hubscher, S.G. Central perivenulitis: a common and potentially important finding in late posttransplant liver biopsies. Liver Transpl 2008;14:596-600. Cerca con Google

[7] Krasinskas, A.M., A.J. Demetris, J.J. Poterucha, and S.C. Abraham The prevalence and natural history of untreated isolated central perivenulitis in adult allograft livers. Liver Transpl 2008;14:625-632. Cerca con Google

[8] Lovell, M.O., K.V. Speeg, G.A. Halff, D.K. Molina, and F.E. Sharkey Acute hepatic allograft rejection: a comparison of patients with and without centrilobular alterations during first rejection episode. Liver Transpl 2004;10:369-373. Cerca con Google

[9] Demetris, A.J., K. Ruppert, I. Dvorchik, A. Jain, M. Minervini, M.A. Nalesnik, et al. Real-time monitoring of acute liver-allograft rejection using the Banff schema. Transplantation 2002;74:1290-1296. Cerca con Google

[10] Ormonde, D.G., W.B. de Boer, A. Kierath, R. Bell, K.B. Shilkin, A.K. House, et al. Banff schema for grading liver allograft rejection: utility in clinical practice. Liver Transpl Surg 1999;5:261-268. Cerca con Google

[11] Wiesner, R.H., A.J. Demetris, S.H. Belle, E.C. Seaberg, J.R. Lake, R.K. Zetterman, et al. Acute hepatic allograft rejection: incidence, risk factors, and impact on outcome. Hepatology 1998;28:638-645. Cerca con Google

[12] Banff schema for grading liver allograft rejection: an international consensus document. Hepatology 1997;25:658-663. Cerca con Google

[13] Afzali, B., R.I. Lechler, and M.P. Hernandez-Fuentes Allorecognition and the alloresponse: clinical implications. Tissue Antigens 2007;69:545-556. Cerca con Google

[14] Stefanova, I., J.R. Dorfman, M. Tsukamoto, and R.N. Germain On the role of self-recognition in T cell responses to foreign antigen. Immunol Rev 2003;191:97-106. Cerca con Google

[15] Afzali, B., G. Lombardi, and R.I. Lechler Pathways of major Cerca con Google

histocompatibility complex allorecognition. Curr Opin Organ Transplant 2008;13:438-444. Cerca con Google

[16] Strom, T.B., N.L. Tilney, C.B. Carpenter, and G.J. Busch Identity and cytotoxic capacity of cells infiltrating renal allografts. N Engl J Med 1975;292:1257-1263. Cerca con Google

[17] Kroemer, A., K. Edtinger, and X.C. Li The innate natural killer cells in transplant rejection and tolerance induction. Curr Opin Organ Transplant 2008;13:339-343. Cerca con Google

[18] Strom, T.B. and M. Koulmanda Recently discovered T cell subsets cannot keep their commitments. J Am Soc Nephrol 2009;20:1677-1680. Cerca con Google

[19] Bettelli, E., Y. Carrier, W. Gao, T. Korn, T.B. Strom, M. Oukka, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006;441:235-238. Cerca con Google

[20] Korn, T., E. Bettelli, W. Gao, A. Awasthi, A. Jager, T.B. Strom, et al. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 2007;448:484-487. Cerca con Google

[21] Weaver, C.T. and R.D. Hatton Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective. Nat Rev Immunol 2009;9:883- 889. Cerca con Google

[22] Li, X.C., M.S. Zand, Y. Li, X.X. Zheng, and T.B. Strom On Cerca con Google

histocompatibility barriers, Th1 to Th2 immune deviation, and the nature of the allograft responses. J Immunol 998;161:2241-2247. Cerca con Google

[23] Strom, T.B., P. Roy-Chaudhury, R. Manfro, X.X. Zheng, P.W. Nickerson, K. Wood, et al. The Th1/Th2 paradigm and the allograft response. Curr Opin Immunol 1996;8:688-693. Cerca con Google

[24] Hall, B.M., N.W. Pearce, K.E. Gurley, and S.E. Dorsch Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. III. Further characterization of the CD4+ suppressor cell and its mechanisms of action. J Exp Med 1990;171:141-157. Cerca con Google

[25] Sakaguchi, S., N. Sakaguchi, M. Asano, M. Itoh, and M. Toda Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995;155:1151-1164. Cerca con Google

[26] Waldmann, H., T.C. Chen, L. Graca, E. Adams, S. Daley, S. Cobbold, et al. Regulatory T cells in transplantation. Semin Immunol 2006;18:111-119. Cerca con Google

[27] Mitchell, P., B. Afzali, G. Lombardi, and R.I. Lechler The T helper 17-regulatory T cell axis in transplant rejection and tolerance. Curr Opin Organ Transplant 2009;14:326-331. Cerca con Google

[28] Koenen, H.J., R.L. Smeets, P.M. Vink, E. van Rijssen, A.M. Boots, and I. Joosten Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells. Blood 2008;112:2340-2352. Cerca con Google

[29] Stumhofer, J.S., J.S. Silver, A. Laurence, P.M. Porrett, T.H. Harris, L.A. Turka, et al. Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol 2007;8:1363-1371. Cerca con Google

[30] Barber, D.L., E.J. Wherry, and R. Ahmed Cutting edge: rapid in vivo killing by memory CD8 T cells. J Immunol 2003;171:27-31. Cerca con Google

[31] Sallusto, F., A. Langenkamp, J. Geginat, and A. Lanzavecchia Functional subsets of memory T cells identified by CCR7 expression. Curr Top Microbiol Immunol 2000;251:167-171. Cerca con Google

[32] Sallusto, F., J. Geginat, and A. Lanzavecchia Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol 2004;22:745-763. Cerca con Google

[33] Bingaman, A.W. and D.L. Farber Memory T cells in transplantation: generation, function, and potential role in rejection. Am J Transplant 2004;4:846-852. Cerca con Google

[34] Welsh, R.M. and L.K. Selin No one is naive: the significance of heterologous T-cell immunity. Nat Rev Immunol 2002;2:417-426. Cerca con Google

[35] Schenk, A.D., T. Nozaki, M. Rabant, A. Valujskikh, and R.L. Fairchild Donor-reactive CD8 memory T cells infiltrate cardiac allografts within 24-h posttransplant in naive recipients. Am J Transplant 2008;8:1652-1661. Cerca con Google

[36] Zheng, X.X., T.G. Markees, W.W. Hancock, Y. Li, D.L. Greiner, X.C. Li, et al. CTLA4 signals are required to optimally induce allograft tolerance with combined donor-specific transfusion and anti-CD154 monoclonal antibody treatment. J Immunol 1999;162:4983-4990. Cerca con Google

[37] Pearl, J.P., J. Parris, D.A. Hale, S.C. Hoffmann, W.B. Bernstein, K.L. McCoy, et al. Immunocompetent T-cells with a memory-like phenotype are the dominant cell type following antibody-mediated T-cell depletion. Am J Transplant 2005;5:465-474. Cerca con Google

[38] Araki, K., A.P. Turner, V.O. Shaffer, S. Gangappa, S.A. Keller, M.F. Bachmann, et al. mTOR regulates memory CD8 T-cell differentiation. Nature 2009;460:108-112. Cerca con Google

[39] Neuberger, J. Incidence, timing, and risk factors for acute and chronic rejection. Liver Transpl Surg 1999;5:S30-36. Cerca con Google

[40] Neuberger, J. and D.H. Adams What is the significance of acute liver allograft rejection? J Hepatol 1998;29:143-150. Cerca con Google

[41] Hayashi, M., E.B. Keeffe, S.M. Krams, O.M. Martinez, O.N. Ojogho, S.K. So, et al. Allograft rejection after liver transplantation for autoimmune liver diseases. Liver Transpl Surg 1998;4:208-214. Cerca con Google

[42] Berlakovich, G.A., S. Rockenschaub, S. Taucher, K. Kaserer, F. Muhlbacher, and R. Steiniger Underlying disease as a predictor for rejection after liver transplantation. Arch Surg 1998;133:167-172. Cerca con Google

[43] Adams, D.H., S.G. Hubscher, J.M. Neuberger, P. McMaster, E. Elias, and J.A. Buckels Reduced incidence of rejection in patients undergoing liver transplantation for chronic hepatitis B. Transplant Proc 1991;23:1436-1437. Cerca con Google

[44] Farges, O., F. Saliba, H. Farhamant, D. Samuel, A. Bismuth, M. Reynes, et al. Incidence of rejection and infection after liver transplantation as a function of the primary disease: possible influence of alcohol and polyclonal immunoglobulins. Hepatology 1996;23:240-248. Cerca con Google

[45] Gomez-Manero, N., J.I. Herrero, J. Quiroga, B. Sangro, F. Pardo, J.A. Cienfuegos, et al. Prognostic model for early acute rejection after liver transplantation. Liver Transpl 2001;7:246-254. Cerca con Google

[46] McVicar, J.P., K.V. Kowdley, C.E. Bacchi, D. Barr, C.L. Marsh, J.D. Perkins, et al. The natural history of untreated focal allograft rejection in liver transplant recipients. Liver Transpl Surg 1996;2:154-160. Cerca con Google

[47] Tippner, C., B. Nashan, K. Hoshino, E. Schmidt-Sandte, K. Akimaru, K.H. Boker, et al. Clinical and subclinical acute rejection early after liver transplantation: contributing factors and relevance for the long-term course. Transplantation 2001;72:1122-1128. Cerca con Google

[48] Fisher, L.R., K.S. Henley, and M.R. Lucey Acute cellular rejection after liver transplantation: variability, morbidity, and mortality. Liver Transpl Surg 1995;1:10-15. Cerca con Google

[49] Mor, E., T.A. Gonwa, B.S. Husberg, R.M. Goldstein, and G.B. Klintmalm Late-onset acute rejection in orthotopic liver transplantation--associated risk factors and outcome. Transplantation 1992;54:821-824. Cerca con Google

[50] Anand, A.C., S.G. Hubscher, B.K. Gunson, P. McMaster, and J.M. Neuberger Timing, significance, and prognosis of late acute liver allograft rejection. Transplantation 1995;60:1098-1103. Cerca con Google

[51] Wiesner, R.H., R.M. Goldstein, J.P. Donovan, C.M. Miller, J.R. Lake, and M.R. Lucey The impact of cyclosporine dose and level on acute rejection and patient and graft survival in liver transplant recipients. Liver Transpl Surg 1998;4:34-41. Cerca con Google

[52] Dousset, B., F. Conti, B. Cherruau, A. Louvel, O. Soubrane, D. Houssin, et al. Is acute rejection deleterious to long-term liver allograft function? J Hepatol 1998;29:660-668. Cerca con Google

[53] Grinyo, J.M. and J.M. Cruzado Mycophenolate mofetil and calcineurininhibitor reduction: recent progress. Am J Transplant 2009;9:2447-2452. Cerca con Google

[54] Abouljoud, M.S., M.F. Levy, and G.B. Klintmalm Hyperlipidemia after liver transplantation: long-term results of the FK506/cyclosporine A US Multicenter Trial. US Multicenter Study Group. Transplant Proc 1995;27:1121-1123. Cerca con Google

[55] Jindal, R.M., R.A. Sidner, and M.L. Milgrom Post-transplant diabetes mellitus. The role of immunosuppression. Drug Saf 1997;16:242-257. Cerca con Google

[56] Mor, E., D. Facklam, J. Hasse, P. Sheiner, S. Emre, M. Schwartz, et al. Weight gain and lipid profile changes in liver transplant recipients: longterm results of the American FK506 Multicenter Study. Transplant Proc 1995;27:1126. Cerca con Google

[57] Pham, H., A. Lemoine, M. Salvucci, D. Azoulay, N. Frenoy, D. Samuel, et al. Occurrence of gammopathies and lymphoproliferative disorders in liver transplant recipients randomized to tacrolimus (FK506)- or cyclosporinebased Cerca con Google

immunosuppression. Liver Transpl Surg 1998;4:146-151. Cerca con Google

[58] Kowalski, R.J., D.R. Post, R.B. Mannon, A. Sebastian, H.I. Wright, G. Sigle, et al. Assessing relative risks of infection and rejection: a metaanalysis using an immune function assay. Transplantation 2006;82:663-668. Cerca con Google

[59] Xue, F., J. Zhang, L. Han, Q. Li, N. Xu, T. Zhou, et al. Immune cell functional assay in monitoring of adult liver transplantation recipients with infection. Transplantation 2010;89:620-626. Cerca con Google

[60] Cabrera, R., M. Ararat, C. Soldevila-Pico, L. Dixon, J.J. Pan, R. Firpi, et al. Using an immune functional assay to differentiate acute cellular rejection from recurrent hepatitis C in liver transplant patients. Liver Transpl 2009;15:216-222. Cerca con Google

[61] Mendler, M., H. Kwok, E. Franco, P. Baron, J. Weissman, and O. Ojogho Monitoring peripheral blood CD4+ adenosine triphosphate activity in a liver transplant cohort: insight into the interplay between hepatitis C virus infection and cellular immunity. Liver Transpl 2008;14:1313-1322. Cerca con Google

[62] Alkhouri, N., I.A. Hanouneh, R. Lopez, and N.N. Zein Monitoring peripheral blood CD4+ adenosine triphosphate activity in recurrent hepatitis C and its correlation to fibrosis progression. Liver Transpl 2010;16:155-162. Cerca con Google

[63] Verhelst, X.P., R.I. Troisi, I. Colle, A. Geerts, and H. van Vlierberghe Biomarkers for the diagnosis of acute cellular rejection in liver transplant recipients: A review. Hepatol Res 2012. Cerca con Google

[64] Abraham, S.C. and E.E. Furth Receiver operating characteristic analysis of serum chemical parameters as tests of liver transplant rejection and correlation with histology. Transplantation 1995;59:740-746. Cerca con Google

[65] Adams, D.H., L. Wang, S.G. Hubscher, E. Elias, and J.M. Neuberger Soluble interleukin-2 receptors in serum and bile of liver transplant recipients. Lancet 1989;1:469-471. Cerca con Google

[66] Perkins, J.D., D.L. Nelson, J. Rakela, P.M. Grambsch, and R.A. Krom Soluble interleukin-2 receptor level as an indicator of liver allograft rejection. Transplantation 1989;47:77-81. Cerca con Google

[67] Lalli, E., R. Meliconi, R. Conte, A. Mancini, M. Uguccioni, G.F. Stefanini, et al. Serum markers of immune activation and liver allograft rejection. Dig Dis Sci 1992;37:1116-1120. Cerca con Google

[68] Platz, K.P., A.R. Mueller, R. Rossaint, T. Steinmuller, H.P. Lemmens, H. Lobeck, et al. Cytokine pattern during rejection and infection after liver transplantation--improvements in postoperative monitoring? Transplantation 1996;62:1441-1450. Cerca con Google

[69] Kita, Y., Y. Iwaki, A.J. Demetris, and T.E. Starzl Evaluation of sequential serum interleukin-6 levels in liver allograft recipients. Transplantation 1994;57:1037-1041. Cerca con Google

[70] Conti, F., J. Frappier, S. Dharancy, C. Chereau, D. Houssin, B. Weill, et al. Interleukin-15 production during liver allograft rejection in humans. Transplantation 2003;76:210-216. Cerca con Google

[71] Imagawa, D.K., J.M. Millis, K.M. Olthoff, L.J. Derus, D. Chia, L.R. Sugich, et al. The role of tumor necrosis factor in allograft rejection. I. Evidence that elevated levels of tumor necrosis factor-alpha predict rejection following orthotopic liver transplantation. Transplantation 1990;50:219-225. Cerca con Google

[72] Maury, C.P., K. Hockerstedt, A.M. Teppo, I. Lautenschlager, and T.M. Scheinin Changes in serum amyloid A protein and beta-2-microglobulin in association with liver allograft rejection. Transplantation 1984;38:551-553. Cerca con Google

[73] Tilg, H., W. Vogel, W.E. Aulitzky, M. Herold, A. Konigsrainer, R. Margreiter, et al. Evaluation of cytokines and cytokine-induced secondary messages in sera of patients after liver transplantation. Transplantation 1990;49:1074-1080. Cerca con Google

[74] Vivarelli, M., H.M. Smith, N.V. Naoumov, and R. Williams Quantitative assessment of serum beta-2-microglobulin in liver transplant recipients and relationship to liver graft rejection. Eur J Gastroenterol Hepatol 1995;7:1215-1219. Cerca con Google

[75] Minguela, A., A.M. Garcia-Alonso, L. Marin, A. Torio, F. Sanchez-Bueno, J. Bermejo, et al. Evidence of CD28 upregulation in peripheral T cells before liver transplant acute rejection. Transplant Proc 1997;29:499-500. Cerca con Google

[76] Minguela, A., M. Miras, J. Bermejo, F. Sanchez-Bueno, M.R. Lopez-Alvarez, M.R. Moya-Quiles, et al. HBV and HCV infections and acute rejection differentially modulate CD95 and CD28 expression on peripheral blood lymphocytes after liver transplantation. Hum Immunol 2006;67:884-893. Cerca con Google

[77] Pober, J.S. and R.S. Cotran The role of endothelial cells in inflammation. Transplantation 1990;50:537-544. Cerca con Google

[78] Goto, S., T. Noguchi, S.V. Lynch, R.W. Strong, Y. Morotomi, R. Lord, et al. Is regular measurement of adhesion molecules and cytokines useful to predict post-liver transplant complications? Transplant Proc 1998;30:2975-2976. Cerca con Google

[79] Mueller, A.R., K.P. Platz, G.W. Haller, G. Schumacher, N. Rayes, C. Schumacher, et al. Adhesion molecules during adverse events after human liver transplantation. Transplant Proc 1997;29:2822-2824. Cerca con Google

[80] Lang, T., S.M. Krams, J.C. Villanueva, K. Cox, S. So, and O.M. Martinez Differential patterns of circulating intercellular adhesion molecule-1 (cICAM-1) and vascular cell adhesion molecule-1 (cVCAM-1) during liver allograft rejection. Transplantation 1995;59:584-589. Cerca con Google

[81] Ninova, D., R.A. Krom, and R.H. Wiesner Hepatic allograft rejection is associated with increased levels of soluble intercellular adhesion molecule-1. Liver Transpl Surg 1995;1:290-295. Cerca con Google

[82] Testro, A.G., K. Visvanathan, N. Skinner, V. Markovska, P. Crowley, P.W. Angus, et al. Acute allograft rejection in human liver transplant recipients is associated with signaling through toll-like receptor 4. J Gastroenterol Hepatol 2011;26:155-163. Cerca con Google

[83] Rivero, M., J. Crespo, M. Mayorga, E. Fabrega, F. Casafont, and F. Pons-Romero Involvement of the Fas system in liver allograft rejection. Am J Gastroenterol 2002;97:1501-1506. Cerca con Google

[84] Foster, P.F., H.N. Sankary, M. Hart, M. Ashmann, and J.W. Williams Blood and graft eosinophilia as predictors of rejection in human liver transplantation. Transplantation 1989;47:72-74. Cerca con Google

[85] Nagral, A., Z. Ben-Ari, A.P. Dhillon, and A.K. Burroughs Eosinophils in acute cellular rejection in liver allografts. Liver Transpl Surg 1998;4:355-362. Cerca con Google

[86] Barnes, E.J., M.M. Abdel-Rehim, Y. Goulis, M. Abou Ragab, S. Davies, A. Dhillon, et al. Applications and limitations of blood eosinophilia for the diagnosis of acute cellular rejection in liver transplantation. Am J Transplant 2003;3:432-438. Cerca con Google

[87] Dickson, R.C., G.Y. Lauwers, C.B. Rosen, R. Cantwell, D.R. Nelson, and J.Y. Lau The utility of noninvasive serologic markers in the management of early allograft rejection in liver transplantation recipients. Transplantation 1999;68:247-253. Cerca con Google

[88] Nagral, A., P. Butler, C.A. Sabin, K. Rolles, and A.K. Burroughs Alphaglutathione- S-transferase in acute rejection of liver transplant recipients. Transplantation 1998;65:401-405. Cerca con Google

[89] Platz, K.P., A.R. Mueller, G.W. Haller, C. Muller, M. Wenig, R. Neuhaus, et al. Determination of alpha- and Pi-glutathione--transferase will improve monitoring after liver transplantation. Transplant Proc 1997;29:2827-2829. Cerca con Google

[90] Trull, A.K., S.P. Facey, G.W. Rees, D.G. Wight, G. Noble-Jamieson, C. Joughin, et al. Serum alpha-glutathione S-transferase--a sensitive marker of hepatocellular damage associated with acute liver allograft rejection. Transplantation 1994;58:1345-1351. Cerca con Google

[91] Feussner, G., C. Stech, J. Dobmeyer, H. Schaefer, G. Otto, and R. Ziegler Serum amyloid A protein (SAA): a marker for liver allograft rejection in humans. Clin Investig 1994;72:1007-1011. Cerca con Google

[92] Li, H., H.Y. Xie, L. Zhou, X.W. Feng, W.L. Wang, T.B. Liang, et al. Copy number variation in CCL3L1 gene is associated with susceptibility to acute rejection in patients after liver transplantation. Clin Transplant 2012;26:314-321. Cerca con Google

[93] Dhillon, N., L. Walsh, B. Kruger, S.C. Ward, J.H. Godbold, M. Radwan, et al. A single nucleotide polymorphism of Toll-like receptor 4 identifies the risk of developing graft failure after liver transplantation. J Hepatol 2010;53:67-72. Cerca con Google

[94] Massoud, O., J. Heimbach, K. Viker, A. Krishnan, J. Poterucha, W. Sanchez, et al. Noninvasive diagnosis of acute cellular rejection in liver transplant recipients: a proteomic signature validated by enzyme-linked immunosorbent assay. Liver Transpl 2011;17:723-732. Cerca con Google

[95] Cheng, J., L. Zhou, J.W. Jiang, Y.S. Qin, H.Y. Xie, X.W. Feng, et al. Proteomic analysis of differentially expressed proteins in rat liver allografts developed acute rejection. Eur Surg Res 2010;44:43-51. Cerca con Google

[96] Kobayashi, S., H. Nagano, S. Marubashi, N. Hama, T.A. Eguchi, Y. Takeda, et al. Guanylate-binding protein 2 mRNA in peripheral blood leukocytes of liver transplant recipients as a marker for acute cellular rejection. Transpl Int 2010;23:390-396. Cerca con Google

[97] Farid, W.R., Q. Pan, A.J. van der Meer, P.E. de Ruiter, V. Cerca con Google

Ramakrishnaiah, J. de Jonge, et al. Hepatocyte-derived microRNAs as serum biomarkers of hepatic injury and rejection after liver transplantation. Liver Transpl 2012;18:290-297. Cerca con Google

[98] Seiler, C.A., J.F. Dufour, E.L. Renner, M. Schilling, M.W. Buchler, P. Bischoff, et al. Primary liver disease as a determinant for acute rejection after liver transplantation. Langenbecks Arch Surg 1999;384:259-263. Cerca con Google

[99] Rolles, K., B.R. Davidson, and A.K. Burroughs A pilot study of immunosuppressive monotherapy in liver transplantation: tacrolimus versus microemulsified cyclosporin. Transplantation 1999;68:1195-1198. Cerca con Google

[100] O'Grady, J.G., P. Hardy, A.K. Burroughs, and D. Elbourne Randomized controlled trial of tacrolimus versus microemulsified cyclosporin (TMC) in liver transplantation: poststudy surveillance to 3 years. Am J Transplant Cerca con Google

2007;7:137-141. Cerca con Google

[101] Cholongitas, E., V. Shusang, G. Germani, E. Tsochatzis, M.L. Raimondo, L. Marelli, et al. Long-term follow-up of immunosuppressive monotherapy in liver transplantation: tacrolimus and microemulsified cyclosporin. Clin Cerca con Google

Transplant 2011;25:614-624. Cerca con Google

[102] Datta Gupta, S., M. Hudson, A.K. Burroughs, R. Morris, K. Rolles, P. Amlot, et al. Grading of cellular rejection after orthotopic liver transplantation. Hepatology 1995;21:46-57. Cerca con Google

[103] Calne, R. WOFIE hypothesis: some thoughts on an approach toward allograft tolerance. Transplant Proc 1996;28:1152. Cerca con Google

[104] Knechtle, S.J., J.A. Wolfe, J. Burchette, F. Sanfilippo, and R.R. Bollinger Infiltrating cell phenotypes and patterns associated with hepatic allograft rejection or acceptance. Transplantation 1987;43:169-172. Cerca con Google

[105] Gomez, R., E. Moreno, C. Loinaz, I. Gonzalez-Pinto, I. Garcia, M. Marcello, et al. [Liver transplantation using grafts from donors over 65]. Rev Esp Enferm Dig 1995;87:217-220. Cerca con Google

[106] Kiuchi, T., H.J. Schlitt, K.J. Oldhafer, B. Nashan, B. Ringe, T. Kitai, et al. Backgrounds of early intragraft immune activation and rejection in liver transplant recipients. Impact of graft reperfusion quality. Transplantation 1995;60:49-55. Cerca con Google

[107] Opelz, G., D.P. Sengar, M.R. Mickey, and P.I. Terasaki Effect of blood transfusions on subsequent kidney transplants. Transplant Proc 1973;5:253-259. Cerca con Google

[108] Blajchman, M.A. Transfusion immunomodulation or TRIM: what does it mean clinically? Hematology 2005;10 Suppl 1:208-214. Cerca con Google

[109] Blajchman, M.A. Immunomodulatory effects of allogeneic blood transfusions: clinical manifestations and mechanisms. Vox Sang 1998;74 Suppl 2:315-319. Cerca con Google

[110] Bordin, J.O. and M.A. Blajchman Immunosuppressive effects of allogeneic blood transfusions: implications for the patient with a malignancy. Hematol Oncol Clin North Am 1995;9:205-218. Cerca con Google

[111] Bordin, J.O., N.M. Heddle, and M.A. Blajchman Biologic effects of leukocytes present in transfused cellular blood products. Blood 1994;84:1703-1721. Cerca con Google

[112] Raimondo, M.L. and A.K. Burroughs Single-agent immunosuppression after liver transplantation: what is possible? Drugs 2002;62:1587-1597. Cerca con Google

[113] Weir, M.R., M. Hall-Craggs, S.Y. Shen, J.N. Posner, S.V. Alongi, F.J. Dagher, et al. The prognostic value of the eosinophil in acute renal allograft rejection. Transplantation 1986;41:709-712. Cerca con Google

[114] Trull, A., L. Steel, J. Cornelissen, T. Smith, L. Sharples, N. Cary, et al. Association between blood eosinophil counts and acute cardiac and pulmonary allograft rejection. J Heart Lung Transplant 1998;17:517-524. Cerca con Google

[115] Hughes, V.F., A.K. Trull, O. Joshi, and G.J. Alexander Monitoring eosinophil activation and liver function after liver transplantation. Transplantation 1998;65:1334-1339. Cerca con Google

[116] Nagral, A., A. Quaglia, C.A. Sabin, A.P. Dhillon, C.P. Bearcroft, A. Millar, et al. Blood and graft eosinophils in acute cellular rejection of liver allografts. Transplant Proc 2001;33:2588-2593. Cerca con Google

[117] de Groen, P.C., G.M. Kephart, G.J. Gleich, and J. Ludwig The eosinophil as an effector cell of the immune response during hepatic allograft rejection. Hepatology 1994;20:654-662. Cerca con Google

[118] Kishi, Y., Y. Sugawara, S. Tamura, J. Kaneko, N. Akamatsu, J. Togashi, et al. Is blood eosinophilia an effective predictor of acute rejection in living donor liver transplantation? Transpl Int 2005;18:1147-1151. Cerca con Google

[119] Bartlett, A.S., R. Ramadas, S. Furness, E. Gane, and J.L. McCall The natural history of acute histologic rejection without biochemical graft dysfunction in orthotopic liver transplantation: a systematic review. Liver Transpl 2002;8:1147-1153. Cerca con Google

[120] Hughes, V.F., D.G. Melvin, M. Niranjan, G.A. Alexander, and A.K. Trull Clinical validation of an artificial neural network trained to identify acute allograft rejection in liver transplant recipients. Liver Transpl 2001;7:496-503. Cerca con Google

[121] Le Moine, A., M. Goldman, and D. Abramowicz Multiple pathways to allograft rejection. Transplantation 2002;73:1373-1381. Cerca con Google

[122] Malavasi, F., A. Funaro, S. Roggero, A. Horenstein, L. Calosso, and K. Mehta Human CD38: a glycoprotein in search of a function. Immunol Today 1994;15:95-97. Cerca con Google

[123] Belles-Isles, M., I. Houde, J.G. Lachance, R. Noel, I. Kingma, and R. Roy Monitoring of cytomegalovirus infections by the CD8+CD38+ T-cell subset in kidney transplant recipients. Transplantation 1998;65:279-282. Cerca con Google

[124] Walker, M.R., D.J. Kasprowicz, V.H. Gersuk, A. Benard, M. Van Landeghen, J.H. Buckner, et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J Clin Invest 2003;112:1437-1443. Cerca con Google

[125] Khattri, R., T. Cox, S.A. Yasayko, and F. Ramsdell An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 2003;4:337-342. Cerca con Google

[126] Wang, S., J. Jiang, Q. Guan, Z. Lan, H. Wang, C.Y. Nguan, et al. Reduction of Foxp3-expressing regulatory T cell infiltrates during the progression of renal allograft rejection in a mouse model. Transpl Immunol 2008;19:93-102. Cerca con Google

[127] Joffre, O., T. Santolaria, D. Calise, T. Al Saati, D. Hudrisier, P. Romagnoli, et al. Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes. Nat Med 2008;14:88-92. Cerca con Google

[128] Yang, H., R. Ding, V.K. Sharma, F.S. Hilaire, M. Lagman, B. Li, et al. Hyperexpression of Foxp3 and IDO during acute rejection of islet allografts. Transplantation 2007;83:1643-1647. Cerca con Google

[129] Chen, L., E. Ahmed, T. Wang, Y. Wang, J. Ochando, A.S. Chong, et al. TLR signals promote IL-6/IL-17-dependent transplant rejection. J Immunol 2009;182:6217-6225. Cerca con Google

[130] Kruger, B., S. Krick, N. Dhillon, S.M. Lerner, S. Ames, J.S. Bromberg, et al. Donor Toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation. Proc Natl Acad Sci U S A Cerca con Google

2009;106:3390-3395. Cerca con Google

[131] Kolls, J.K. and A. Linden Interleukin-17 family members and inflammation. Immunity 2004;21:467-476. Cerca con Google

[132] Fossiez, F., O. Djossou, P. Chomarat, L. Flores-Romo, S. Ait-Yahia, C. Maat, et al. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med 1996;183:2593-2603. Cerca con Google

[133] Kennedy, J., D.L. Rossi, S.M. Zurawski, F. Vega, Jr., R.A. Kastelein, J.L. Wagner, et al. Mouse IL-17: a cytokine preferentially expressed by alpha beta TCR + CD4-CD8-T cells. J Interferon Cytokine Res 1996;16:611-617. Cerca con Google

[134] Attur, M.G., R.N. Patel, S.B. Abramson, and A.R. Amin Interleukin-17 upregulation of nitric oxide production in human osteoarthritis cartilage. Arthritis Rheum 1997;40:1050-1053. Cerca con Google

[135] Hsieh, H.G., C.C. Loong, W.Y. Lui, A. Chen, and C.Y. Lin IL-17 expression as a possible predictive parameter for subclinical renal allograft rejection. Transpl Int 2001;14:287-298. Cerca con Google

[136] Loong, C.C., H.G. Hsieh, W.Y. Lui, A. Chen, and C.Y. Lin Evidence for the early involvement of interleukin 17 in human and experimental renal allograft rejection. J Pathol 2002;197:322-332. Cerca con Google

[137] Boleslawski, E., S. BenOthman, S. Grabar, L. Correia, P. Podevin, S. Chouzenoux, et al. CD25, CD28 and CD38 expression in peripheral blood lymphocytes as a tool to predict acute rejection after liver transplantation. Clin Transplant 2008;22:494-501. Cerca con Google

[138] Hazzan, M., M. Labalette, C. Noel, G. Lelievre, and J.P. Dessaint Recall response to cytomegalovirus in allograft recipients: mobilization of CD57+, CD28+ cells before expansion of CD57+, CD28- cells within the CD8+ T lymphocyte compartment. Transplantation 1997;63:693-698. Cerca con Google

[139] Engstrand, M., A.K. Lidehall, T.H. Totterman, B. Herrman, B.M. Eriksson, and O. Korsgren Cellular responses to cytomegalovirus in immunosuppressed patients: circulating CD8+ T cells recognizing CMVpp65 are present but display functional impairment. Clin Exp Immunol 2003;132:96-104. Cerca con Google

[140] Caldwell, C.C., T. Okaya, A. Martignoni, T. Husted, R. Schuster, and A.B. Lentsch Divergent functions of CD4+ T lymphocytes in acute liver inflammation and injury after ischemia-reperfusion. Am J Physiol Gastrointest Liver Physiol 2005;289:G969-976. Cerca con Google

[141] Yoshida, S., A. Haque, T. Mizobuchi, T. Iwata, M. Chiyo, T.J. Webb, et al. Anti-type V collagen lymphocytes that express IL-17 and IL-23 induce rejection pathology in fresh and well-healed lung transplants. Am J Transplant 2006;6:724-735. Cerca con Google

[142] Van Kooten, C., J.G. Boonstra, M.E. Paape, F. Fossiez, J. Banchereau, S. Lebecque, et al. Interleukin-17 activates human renal epithelial cells in vitro and is expressed during renal allograft rejection. J Am Soc Nephrol 1998;9:1526-1534. Cerca con Google

[143] Antonysamy, M.A., W.C. Fanslow, F. Fu, W. Li, S. Qian, A.B. Troutt, et al. Evidence for a role of IL-17 in alloimmunity: a novel IL-17 antagonist promotes heart graft survival. Transplant Proc 1999;31:93. Cerca con Google

[144] Li, J., E. Simeoni, S. Fleury, J. Dudler, E. Fiorini, L. Kappenberger, et al. Gene transfer of soluble interleukin-17 receptor prolongs cardiac allograft survival in a rat model. Eur J Cardiothorac Surg 2006;29:779-783. Cerca con Google

Download statistics

Solo per lo Staff dell Archivio: Modifica questo record