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Chapter 139 : Molecular Characterization of Rejection in Solid Organ Transplantation

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Abstract:

Improved knowledge of the alloimmune repertoire, development and clinical application of new therapeutics, advances in surgical techniques, and effective infection prophylaxis have advanced transplantation to the forefront of modern medicine. This chapter provides an outline of the immune cascade contributing to allograft rejection, emphasizes molecular protocols that have been applied to investigate gene expression, and summarizes molecular correlates of rejection of human kidney, heart, lung, liver, or pancreatic islet cell allografts. The advent of an in vitro assay, PCR, to amplify the nucleic acid sequences has greatly reduced the amount of starting material required for the identification and measurement of mRNAs in biological samples. Cytotoxic T lymphocytes (CTL) destroy target cells via multiple effector mechanisms. Cardiac allograft vasculopathy (CAV) is a form of chronic rejection in which intimal thickening leads to accelerated transplant coronary artery disease. Acute rejection of lung allografts is distinguished by perivas-cular mononuclear cell infiltration of venules and arterioles. Chronic rejection of lung allografts is a major diagnostic and therapeutic challenge and a significant contributor to morbidity and mortality. Nucleic acid-based strategies have proven useful for the detection and quantification of gene expression in the clinic. Global expression profiling with technologies such as microarrays will add to our knowledge and provide further insights into molecular pathways, and several pathways are likely to be responsible for the rejection process. The ultimate objective, personalized medicine for the transplant recipient, is an accomplishable goal.

Citation: Hartono C, Dadhania D, Suthanthiran M. 2006. Molecular Characterization of Rejection in Solid Organ Transplantation, p 1244-1259. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch139

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Image of FIGURE 1
FIGURE 1

Design and construction of DNA competitors. A DNA competitor of granzyme B cDNA was prepared by digestion of the 180-bp naturally occurring product of PCR (GenBank accession no. M28879) with MseI and ligation of the subfragments with a 44-bp DNA insert with appropriate cohesive ends at the 5’ and 3’ ends. A DNA competitor of perforin cDNA was prepared by digestion of the 176-bp naturally occurring product of PCR (GenBank accession no. M28393) with N1aIII and ligation of the subfragments with a 36-bp DNA insert. The 274-bp cDNA competitor of cyclophilin was amplified with the use of a modified sense primer that contains the external sense primer at its 5’ end and a 16-bp subfragment internal sense primer at its 3’ end corresponding to sequences 302 to 317 within the naturally occurring product of PCR (GenBank accession no. M60857). (Reprinted from reference with permission.)

Citation: Hartono C, Dadhania D, Suthanthiran M. 2006. Molecular Characterization of Rejection in Solid Organ Transplantation, p 1244-1259. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch139
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Image of FIGURE 2
FIGURE 2

Receiver operator characteristic curve of mRNA levels. The fractions of true-positive results (sensitivity) and false-positive results (1—specificity) for perforin mRNA levels, granzyme B mRNA levels, and cyclophilin B mRNA levels as markers of acute rejection are shown. The calculated areas under the curve were 0.86 for perforin mRNA levels, 0.86 for granzyme B mRNA levels, and 0.58 for cyclophilin B mRNA levels. A value of 0.5 is no better than expected by chance, and a value of 1.0 reflects a perfect indicator. (Reprinted from reference with permission.)

Citation: Hartono C, Dadhania D, Suthanthiran M. 2006. Molecular Characterization of Rejection in Solid Organ Transplantation, p 1244-1259. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch139
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Image of FIGURE 3
FIGURE 3

Levels (mean SE) of perforin mRNA, granzyme B mRNA, and cyclophilin B mRNA in sequential urine samples. The mRNAs were measured in urine samples obtained during the first 9 days after transplantation, using competitive quantitative PCR assay. The levels of perforin mRNA and granzyme B mRNA but not those of cyclophilin B mRNA were higher in the 8 patients in whom acute rejection developed within the first 10 days after transplantation than in the 29 patients in whom acute rejection did not develop within the first 10 days after transplantation. The respective numbers of urine samples obtained from the patients with an episode of acute rejection and those without such an episode were as follows: 6 and 43 on day 1, 2, or 3 after transplantation; 5 and 26 on day 4, 5, or 6; and 6 and 14 on day 7, 8, or 9. Means, SEs, and values were estimated with use of a mixed-level two-way analysis of variance. In all cases, log-transformed values are shown. (Reprinted from reference with permission.)

Citation: Hartono C, Dadhania D, Suthanthiran M. 2006. Molecular Characterization of Rejection in Solid Organ Transplantation, p 1244-1259. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch139
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Image of FIGURE 4
FIGURE 4

Receiver operating characteristic curve of mRNA and rRNA levels. The fractions of true-positive results and false-positive results for IP-10 mRNA levels, CXCR3 mRNA levels, and 18S rRNA levels as markers of acute rejection are shown. Levels of mRNAs were measured with the use of real-time quantitative PCR assay. The calculated areas under the curve were 0.903 for IP-10 mRNA levels, 0.762 for CXCR3 mRNA levels, and 0.574 for 18S rRNA levels. A value of 0.5 is no better than expected by chance, and a value of 1.0 reflects a perfect indicator. (Reprinted from reference with permission.)

Citation: Hartono C, Dadhania D, Suthanthiran M. 2006. Molecular Characterization of Rejection in Solid Organ Transplantation, p 1244-1259. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch139
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References

/content/book/10.1128/9781555815905.ch139
1. Agostini, C.,, F. Calabrese,, F. Rea,, M. Facco,, A. Tosoni,, M. Loy,, G. Binotto,, M. Valente,, L. Trentin, and , G. Semenzato. 2001. CXCR3 and its ligand CXCL10 are expressed by inflammatory cells infiltrating lung allograft and mediate chemotaxis of T cells at sites of rejection. Am. J. Pathol. 158:17031711.
2. Akalin, E.,, R. C. Hendrix,, R. G. Polavarapu,, T. C. Pearson,, J. F. Neylan,, C. P. Larsen. and , F. G. Lakkis. 2001. Gene expression analysis in human renal allograft biopsy samples using high-density oligoarray technology. Transplantation 72:948953.
3. Akira, S., and , K. Takeda. 2004. Toll-like receptor signaling. Nat. Rev. Immunol. 4:499511.
4. Arcasoy, S. M., and , R. M. Kotloff. 1999. Lung transplantation. N. Engl. J. Med. 340:10811091.
5. Autieri, M. S.,, E. Keleman,, J. P. Gaughan, and , H. Eisen. 2004. Early growth responsive gene (Egr)-1 expression correlates with cardiac allograft rejection. Transplantation 78:107111.
6. Autieri, M. V.,, S. Kelemen,, B. A. Thomas,, E. D. Feller,, B. I. Goldman, and , H. J. Eisen. 2002. Allograft inflammatory factor-1 expression correlates with cardiac rejection and development of cardiac allograft vasculopathy. Circulation 106:22182223.
7. Bartlett, A. S. R.,, J. L. McCall,, R. Ameratunga,, M. L. Yeong,, E. Gane, and , S. R. Munn. 2003. Analysis of intragraft gene and protein expression of the costi-mulatory molecules, CD80, CD86 and CD154, in ortho-topic liver transplant recipients. Am. J. Transplant. 3:13631368.
8. Belperio, J. A.,, M. D. Burdick,, M. P. Keane,, Y. Y. Xue,, J. P. Lynch III,, B. L. Daugherty,, S. L. Kunkel, and , R. M. Strieter. 2000. The role of the CC chemokine, RANTES, in acute lung allograft rejection. J. Immunol. 165:461472.
9. Belperio, J. A.,, M. P. Keane,, M. D. Burdick., J. P. Lynch III,, Y. Y. Xue,, K. Li,, D. J. Ross, and , R. M. Strieter. 2002. Critical role for CXCR3 chemokine biology in the patho-genesis of bronchiolitis obliterans syndrome. J. Immunol. 169:10371049.
10. Belperio, J. A.,, M. P. Keane,, M. D. Burdick,, J. P. Lynch III,, D. A. Zisman,, Y Y Xue,, K. Li,, A. Ardehali,, D. J. Ross, and , R. M. Strieter. 2003. Role of CXCL9/CXCR3 chemokine biology during pathogenesis of acute lung allograft rejection. J. Immunol. 171:48444852.
11. Berggren, W. T.,, T. Takova,, M. C. Olson,, P. S. Eis,, R. W. Kwiatkowski, and , L. M. Smith. 2002. Multiplexed gene expression analysis using the invader RNA assay with MALDI-TOF mass spectrometry detection. Anal. Chem. 74:17451750.
12. Billingham, M. E.,, N. R. B. Cary,, M. E. Hammond,, J. Kemnitz,, C. Marboe,, H. A. McCallister,, D. C. Snovar,, G. L. Winters, and , A. Zerbe. 1990. A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection: heart rejection study group. J. Heart Transplant. 9:587593.
13. Bittmann, I.,, C. Muller,, J. Behr,, J. Groetzner,, L. Frey, and , U. Lohrs. 2004. Fas/FasL and perforin/granzyme pathway in acute rejection and diffuse alveolar damage after allogeneic lung transplantation—a human biopsy study. Virchows Arch. 445:375381.
14. Border, W. A., and , N. A. Noble. 1994. Transforming growth factor β in tissue fibrosis. N. Engl. J. Med. 331:12861292.
15. Bowdish, M. E.,, S. M. Arcasoy,, J. S. Wilt,, J. V. Conte,, R. D. Davis,, E. R. Garrity,, M. L. Hertz,, J. B. Orens,, B. R. Rosengard, and , M. L. Barr. 2004. Surrogate markers and risk factors for chronic lung allograft dysfunction. Am. J. Transplant. 4:11711178.
16. Cafario, A. L. P.,, F. Tona,, A. B. Fortina,, A. Angelini,, S. Piaserico,, A. Gambino,, G. Feltrin,, A. Ramondo,, M. Valente,, S. Iliceto,, G. Thiene, and , G. Gerosa. 2004. Immune and nonimmune predictors of cardiac allograft vasculopathy onset and severity: multivariate risk factor analysis and role of immunosuppression. Am. J. Transplant. 4:962970.
17. Clement, M. V.,, S. Legros-Maida,, D. Israel-Biet,, E. Carnot,, A. Soulie,, R. Reynaud,, J. Guillet,, I. Gandjbakch, and , M. Sasportes. 1994. Perforin and granzyme B expression is associated with severe acute rejection. Evidence for in situ localization in alveolar lymphocytes of lung-transplanted patients. Transplantation 57:322326.
18. Conti, F.,, J. Frappier,, S. Dharancy,, C. Chereau,, D. Houssin,, B. Weill, and , Y. Calmus. 2003. Interleukin-15 production during liver allograft rejection in humans. Transplantation 76:210216.
19. de Blic, J.,, M. Peuchmaur,, F. Carnot,, C. Danel,, M. Deruesne,, P. Reynaud,, P. Scheinmann, and , N. Brousse. 1992. Rejection in lung transplantation—an immunohistochemical study of transbronchial biopsies. Transplantation 54:639644.
20. Demetris., A., et al. 2000. Update of the International Banff Schema for Liver Allograft Rejection: working recommendations for the histopathologic staging and reporting of chronic rejection. Hepatology 31:792799.
21. Demetris, A. J., et al. 1997. Banff schema for grading liver allograft rejection: an international consensus document. Hepatology 25:658663.
22. Ding, R.,, B. Li,, T. Muthukumar,, D. Dadhania,, M. Medeiros,, C. Hartono,, D. Serur,, S. V. Seshan,, V. K. Sharma,, S. Kapur, and , M. Suthanthiran. 2003. CD103 mRNA levels in urinary cells predict acute rejection of renal allografts. Transplantation 75:13071312.
23. Donauer, J.,, B. Rumberger,, M. Klein,, D. Faller,, J. Wilpert,, T. Sparna,, G. Schieren,, R. Rohrbach,, R Dern,, J. Timmer,, P. Pisarski,, G. Kirste, and , G. Walz. 2003. Expression profiling on chronically rejected transplant kidneys. Transplantation 76:539547.
24. Fahmy, N. M.,, M. H. Yamani,, R. C. Starling,, N. B. Ratliff,, J. B. Young,, P. M. McCarthy,, J. Y Feng,, A. C. Novick, and , R. L. Fairchild. 2003. Chemokine and chemokine receptor gene expression indicates acute rejection of human cardiac transplants. Transplantation 75:7279.
25. Fahmy, N. M.,, M. H. Yamani,, R. C. Starling,, N. B. Ratliff,, J. B. Young,, P. M. McCarthy,, J. Y Feng,, A. C. Novick. and , R. L. Fairchild. 2003. Chemokine and receptor-gene expression during early and late acute rejection episodes in human cardiac allografts. Transplantation 75:20442047.
26. Flechner, S. M.,, S. M. Kurian,, S. R. Head,, S. M. Sharp,, T. C. Whisenant,, J. Zhang,, J. D. Chismar,, S. Horvath,, T. Mondala,, T. Gilmartin,, D. J. Cook,, S. A. Kay,, J. R. Walker, and , D. R. Salomon. 2004. Kidney transplant rejection and tissue injury by gene profiling of biopsies and peripheral blood lymphocytes. Am. J. Transplant. 4:14751489.
27. Flechner, S. M.,, S. M. Kurian,, K. Solez,, D. J. Cook,, J. T. Burke,, H. Rollin,, J. A. Hammond,, T. Whisenant,, C. M. Lanigan,, S. R. Head, and , D. R. Salomon. 2004. De novo kidney transplantation without use of calcineurin inhibitors preserves renal structure and function at two years. Am. J. Transplant. 4:17761785.
28. Gimino, V. J.,, J. D. Lande,, T. R. Berryman,, R. A. King, and , M. I. Hertz. 2003. Gene expression profiling of bron-choalveolar lavage cells in acute lung rejection. Am. J. Respir. Crit. Care Med. 168:12371242.
29. Giulietti, A.,, L. Overbergh,, D. Valckx,, B. Decallonne,, R. Bouillon, and , C. Mathieu. 2001. An overview of realtime quantitative PCR: applications to quantify cytokine gene expression. Methods 25:386401.
30. Goddard, S.,, A. Williams,, C. Morland,, S. Qin,, R. Gladue,, S. G. Hubscher, and , D. H. Adams. 2001. Differential expression of chemokines and chemokine receptors shapes the inflammatory response in rejecting human liver transplants. Transplantation 72:19571967.
31. Hadley, G. 2004. Role of integrin CD103 in promoting destruction of renal allografts by CD8+ T cells. Am. J. Transplant. 4:10261032.
32. Han, D.,, X. Xu,, D. Baidal,, J. Leith,, C. Ricordi,, R. Alejandro, and , N. S. Kenyon. 2004. Assessment of cytotoxic lymphocyte gene expression in the peripheral blood of human islet allograft recipients. Diabetes 53:22812290.
33. Han, D.,, X. Xu,, R. L. Pastori,, C. Ricordi, and , N. S. Kenyon. 2002. Elevation of cytotoxic lymphocyte gene expression is predictive of islet allograft rejection in nonhuman primates. Diabetes 51:562566.
34. Hartono, C.,, D. Dadhania, and , M. Suthanthiran. 2004. Noninvasive diagnosis of acute rejection of solid organ transplants. Front. Biosci. 9:145153.
35. Heeger, P. S. 2003. T-cell allorecognition and transplant rejection: a summary and update. Am. J. Transplant. 3:525533.
36. Heng, D.,, L. D. Sharples,, K. McNeil,, S. Stewart,, T. Wreghitt, and , J. Wallwork. 1998. Bronchiolitis oblit-erans syndrome: incidence, natural history, prognosis, and risk factors. J. Heart Lung Transplant. 17:12551263.
37. Jordan, B. R. (ed.). 2001. DNA Microarrays: Gene Expression Applications. Springer, New York, N.Y.
38. Kotsch, K.,, M. F. Mashreghi,, G. Bold,, P. Tretow,, J. Beyer,, M. Matz,, J. Hoerstrup,, J. Pratschke,, R. C. Ding,, M. Suthanthiran,, H. D. Volk, and , P. Reinke. 2004. Enhanced granulysin mRNA expression in urinary sediment in early and delayed acute renal allograft rejection. Transplantation 77:18661875.
39. Krams, S. M.,, J. C. Villaneuva,, M. B. Quinn, and , O. M. Martinez. 1995. Expression of the cytotoxic T cell mediator granzyme B during liver allograft rejection. Transpl. Immunol. 3:162166.
40. Kuijf, M. M. L.,, J. Kwekkeboom,, M.A. Kuijpers,, M. Willems,, P. E. Zondervan,, H. G. M. Niesters,, W. C. J. Hop,, C. E. Hack,, T. Paavonen,, K. Hockerstedt,, H. W Tilanus,, I. Lautenschlager, and , H. J. Metselaar. 2002. Granzyme expression in fine-needle aspirates from liver allografts is increased during acute rejection. Liver Transplant. 8:952956.
41. Lakkis, F. G.,, A. Arakelov,, B. T. Konieczny, and , Y. Inoue. 2000. Immunologic ’ignorance’ of vascularized organ transplants in the absence of secondary lymphoid tissue. Nat. Med. 6:686688.
42. Lantz, P. G.,, W. Abu al-Soud,, R. Knutsson,, B. Hahn-Hagerdal, and , P. Radstrom. 2000. Biotechnical use of polymerase chain reaction for microbiological analysis of biological samples. Biotechnol. Annu. Rev. 5:87130.
43. Li, B.,, C. Hartono,, R. Ding,, V. K. Sharma,, R. Ramaswamy,, B. Qian,, D. Serur,, J. Mouradian,, J. E. Schwartz, and , M. Suthanthiran. 2001. Noninvasive diagnosis of renal-allograft rejection by measurement of messenger RNA for perforin and granzyme B in urine. N. Engl. J. Med. 344:947954.
44. Li, Y.,, J. Yang,, C. Dai,, C. Wu, and , Y. Liu. 2003. Role for integrin-linked kinase in mediating tubular epithelial to mesenchymal transition and renal interstitial fibrogenesis. J. Clin. Investig. 112:503516.
45. Libby, P., and , J. S. Pober. 2001. Chronic rejection. Immunity 14:387397.
46. Lipman, M. L.,, A. C. Stevens,, R. C. Bleackley,, J. H. Helderman,, T. R. McCune,, W. E. Harmon,, M. E. Shapiro,, S. Rosen, and , T. B. Strom. 1992. The strong correlation of cytotoxic T lymphocyte-specific serine protease gene transcripts with renal allograft rejection. Transplantation 53:7379.
47. Lipman, M. L.,, A. C. Stevens, and , T. B. Strom. 1994. Heightened intragraft CTL gene expression in acutely rejecting renal allografts. J. Immunol. 152:51205127.
48. Livak, K. J., and , T. D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods 25:402408.
49. Luster, A. D. 1998. Chemokines—chemotactic cytokines that mediate inflammation. N. Engl. J. Med. 338:436445.
50. Marshall, A., and , J. Hodgson. 1998. DNA chips—an array of possibilities. Nat. Biotechnol. 16:2731.
51. Melter, M.,, A. Exeni,, M. E. J. Reinders,, J. C. Fang,, G. McMahon,, P. Ganz,, W. H. Hancock, and , D. M. Briscoe. 2001. Expression of the chemokine receptor CXCR3 and its ligand IP-10 during human cardiac allograft rejection. Circulation 104:25582564.
52. Morgun, A.,, N. Shulzhenko,, G. F. Rampim,, A. P. Chinellato,, R. V. Z. Diniz,, D. R. Almeida,, M. M. Souza,, M. Franco, and , M. Gerbase-DeLima. 2003. Blood and intragraft CD27 gene expression in cardiac transplant recipients. Clin. Immunol. 107:6064.
53. Munger, J. S.,, X. Huang,, H. Kawakatsu,, M. J. D. Griffiths,, S. L. Dalton,, J. Wu,, J. F. Pittet,, N. Kaminski,, C. Garat,, M. A. Matthay,, D. B. Rifkin, and , D. Sheppard. 1999. The integrin av(36 binds and activates latent TGF(31: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 96:319328.
54. Muthukumar, T.,, R. Ding,, D. Dadhania,, M. Medeiros,, B. Li,, V. K. Sharma,, C. Hartono,, D. Serur,, S. V. Seshan,, H. D. Volk,, P. Reinke,, S. Kapur, and , M. Suthanthiran. 2003. Serine proteinase inhibitor-9, an endogenous blocker of granzyme B/perforin lytic pathway, is hyper-expressed during acute rejection of renal allografts. Transplantation 75:15651570.
55. Nelson, P. J., and , A. M. Krensky. 2001. Chemokines, chemokine receptors, and allograft rejection. Immunity 14:377386.
56. Nickel, P.,, J. Lacha,, S. Ode-Hakim,, B. Sawitzki,, N. Babel,, U. Frei,, H. D. Volk, and , P. Reinke. 2001. Cytotoxic effector molecule gene expression in acute renal allograft rejection: correlation with clinical outcome; histopathology and function of the allograft. Transplantation 72:11581160.
57. Nocera, A.,, A. Tagliamacco,, R. De Palma,, E. Del Galdo,, A. Ferrante,, I. Fontana,, S. Barocci,, F. Ginevri,, D. Rolla,, J. L. Ravetti, and , U. Valente. 2004. Cytokine mRNA expression in chronically rejected human renal allografts. Clin. Transplant. 18:564570.
58. Oh, S. I.,, I. W. Kim,, H. C. Jung,, J. W. Seo,, I. H. Chae,, H. S. Kim, and , B. H. Oh. 2001. Correlation of Fas and Fas ligand expression with rejection status of transplanted heart in human. Transplantation 71:906909.
59. Panzer, U.,, R. R. Reinking,, O. M. Steinmetz,, G. Zahner,, U. Sudbeck,, S. Fehr,, B. Pfalzer,, A. Schneider,, E. Thaiss,, M. Mack,, S. Conrad,, H. Huland,, U. Helmchen, and , R. A. K. Stahl. 2004. CXCR3 and CCR5 positive T-cell recruitment in acute human renal allograft rejection. Transplantation 78:13411350.
60. Pavlakis, M.,, J. Strehlau,, M. Lipman,, M. Shapiro,, W. Maslinski, and , T. B. Strom. 1996. Intragraft IL-15 transcripts are increased in human renal allograft rejection. Transplantation 62:543545.
61. Racusen, L. C.,, K. Solez,, R. B. Colvin,, S. M. Bonsib,, M. C. Castro,, T. Cavallo,, B. P. Croker,, A. J. Demetris,, C. B. Drachenberg,, A. B. Fogo,, P. Furness,, L. W. Gaber,, I. W. Gibson,, D. Glotz,, J. C. Goldberg,, J. Grande,, P. E. Halloran,, H. E. Hansen,, B. Hartley,, P. J. Hayry., C. M. Hill,, E. O. Hoffman,, L. G. Hunsicker,, A. S. Lindblad,, N. Marcussen,, M. J. Mihatsch,, T. Nadasdy,, P. Nikerson,, T. S. Olsen,, J. C. Papadimitriou,, P. S. Randhawa,, D. C. Rayner,, I. Roberts,, S. Rose,, D. Rush,, L. Salinas-Madrigal,, D. R. Salomon,, S. Sund,, E. Taskinen,, K. Trpkov, and , Y. Yamaguchi. 1999. The Banff 97 working classification of renal allograft pathology. Kidney Int. 55:713723.
62. Reinders, M. E.,, J. C. Fang,, W. Wong,, P. Ganz, and , D. Briscoe. 2003. Expression patterns of vascular endothelial growth factor in human cardiac allografts: association with rejection. Transplantation 76:224230.
63. Robertson, H.,, W. K. Wong,, D. Talbot,, A. D. Burt, and , J. A. Kirby. 2001. Tubulitis after renal transplantation: demonstration of an association between CD103+ T cells, transforming growth factor (31 expression and rejection grade. Transplantation 71:306313.
64. Sabek, O.,, M. T. Dorak,, M. Kotb,, A. O. Gaber, and , L. Gaber. 2002. Quantitative detection of T-cell activation markers by real-time PCR in renal transplant rejection and correlation with histopathologic evaluation. Transplantation 74:701707.
65. Saiki, R. K.,, S. Scharf,, F. Faloona,, K. B. Mullis,, G. T. Horn,, H. A. Erlich, and , N. Arnheim. 1985. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230:13501354.
66. Sarwal, M.,, M. S. Chua,, N. Kambham,, S. C. Hsieh,, T. Satterwhite,, M. Masek, and , O. Salvatierra. Jr. 2003. Molecular heterogeneity in acute renal allograft rejection identified by DNA microarray profiling. N. Engl. J. Med. 349:125138.
67. Sarwal, M. M.,, A. Jani,, S. Chang,, P. Huie,, Z. Wang,, O. Salvatierra, Jr.,, C. Clayberger,, R. Sibley,, A. M. Krensky, and , M. Pavlakis. 2001. Granulysin expression is a marker for acute rejection and steroid resistance in human renal transplantation. Hum. Immunol. 62:2131.
68. Sawada, T.,, M. Abe,, K. Kai,, K. Kubota,, S. Fuchinoue, and , S. Teraoka. 2004. (36 integrin is up-regulated in chronic renal allograft dysfunction. Clin. Transplant. 18:525528.
69. Sayegh, M. H., and , L. A. Turka. 1998. The role of T-cell costimulatory activation pathways in transplant rejection. N. Engl. J. Med. 338:18131821.
70. Scherer, A.,, A. Krause,, J. R. Walker,, A. Korn,, D. Niese, and , E. Raulf. 2003. Early prognosis of the development of renal chronic allograft rejection by gene expression profiling of human protocol biopsies. Transplantation 75:13231330.
71. Schoels, M.,, T. J. Dengler,, R. Richter,, S. C. Meuer, and , T. Giese. 2004. Detection of cardiac allograft rejection by real-time PCR analysis of circulating mononuclear cells. Clin. Transplant. 18:513517.
72. Schowengerdt, K. O.,, F. J. Fricker,, K. S. Bahjat, and , S. T. Kuntz. 2000. Increased expression of the lymphocyte early activation marker CD69 in peripheral blood correlates with histologic evidence of cardiac allograft rejection. Transplantation 69:21022107.
73. Segerer, S.,, Y. Cui,, F. Eitner,, T. Goodpaster,, K. L. Hudkins,, M. Mack,, J. P. Cartron,, Y. Colin,, D. Schlondorff, and , C. E. Alpers. 2001. Expression of chemokines and chemokine receptors during human renal transplant rejection. Am. J. Kidney Dis. 37:518531.
74. Shapiro, A. M. J.,, J. R. T. Lakey,, E. A. Ryan,, G. S. Korbutt,, E. Toth,, G. L. Warnock,, N. M. Kneteman, and , R. V. Rajotte. 2000. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N. Engl. J. Med. 343:230238.
75. Sharma, V. K.,, R. M. Bologa,, B. Li,, G.P. Xu,, M. Lagman,, W. Hiscock,, J. Mouradian,, J. Wang,, D. Serur,, V. K. Rao, and , M. Suthanthiran. 1996. Molecular executors of cell death—differential intrarenal expression of Fas ligand, Fas, granzyme B, and perforin during acute and/or chronic rejection of human renal allografts. Transplantation 62:18601866.
76. Sharma, V. K.,, R. M. Bologa,, G. P. Xu,, B. Li,, J. Mouradian,, J. Wang,, D. Serur,, V. Rao, and , M. Suthanthiran. 1996. Intragraft TGF-beta 1 mRNA: a correlate of interstitial fibrosis and chronic allograft nephropathy. Kidney Int. 49:12971303.
77. Sheppard, D.,, C. Rozzo,, L. Starr,, V. Quaranta,, D. J. Erle, and , R. Pytela. 1990. Complete amino acid sequence of a novel integrin β subunit (β6) identified in epithelial cells using the polymerase chain reaction. J. Biol. Chem. 265:1150211507.
78. Shi, R.,, J. Yang,, A. Jaramillo,, N. S. Steward,, A. Aloush,, E. P. Trulock,, G. A. Patterson,, M. Suthanthiran, and , T. Mohanakumar. 2004. Correlation between interleukin-15 and granzyme B expression and acute lung allograft rejection. Transpl. Immunol. 12:103108.
79. Shimkets, R. A. 2004. Gene Expression Profiling: Methods and Protocols. Humana, Totowa, N.J.
80. Shoker, A.,, D. George,, H. Yang, and , M. Baltzan. 2000. Heightened CD40 ligand gene expression in peripheral CD4+ T cells from patients with kidney allograft rejection. Transplantation 70:497505.
81. Shreeniwas, R.,, L. L. Schulman,, M. Narasimhan,, C. C. McGregor, and , C. C. Marboe. 1996. Adhesion molecules (E-selectin and ICAM-1) in pulmonary allograft rejection. Chest 110:11431149.
82. Shulzhenko, N.,, A. Morgun,, M. Franco,, M. M. Souza,, D. R. Almeida,, R. V. Z. Diniz,, A. C. C. Carvalho,, A. Pacheco-Silva, and , M. Gerbase-DeLima. 2001. Expression of CD40 ligand, interferon-gamma and Fas ligand genes in endomyocardial biopsies of human cardiac allografts: correlation with acute rejection. Braz. J. Med. Biol. Res. 34:779784.
83. Shulzhenko, N.,, A. Morgun,, G. F. Rampim,, M. Franco., D. R. Almeida,, R. V. Z. Diniz,, A. C. C. Carvalho, and , M. Gerbase-DeLima. 2001. Monitoring of intragraft and peripheral blood TIRC7 expression as a diagnostic tool for acute cardiac rejection in humans. Hum. Immunol. 62:342347.
84. Shulzhenko, N.,, A. Morgun,, X. X. Zheng,, R. V. Diniz,, D. R. Almeida,, N. Ma,, T. B. Strom, and , M. Gerbase-DeLima. 2001. Intragraft activation of genes encoding cytotoxic T lymphocyte effector molecules precedes the histological evidence of rejection in human cardiac transplantation. Transplantation 72:17051708.
85. Simon, T.,, G. Opelz,, M. Wiesel,, R. C. Ott, and , C. Susal. 2003. Serial peripheral blood perforin and granzyme B gene expression measurements for prediction of acute rejection in kidney graft recipients. Am. J. Transplant. 3:11211127.
86. Simon, T.,, G. Opelz,, M. Wiesel,, S. Pelzl,, R. C. Ott, and , C. Susal. 2004. Serial peripheral blood interleukin-18 and perforin gene expression measurements for prediction of acute kidney graft rejection. Transplantation 77:15891595.
87. Souaze, F.,, A. Ntodou-Thome,, C. Y. Tran,, W. Rostene, and , P. Forgez. 1996. Quantitative RT-PCR: limits and accuracy. BioTechniques 21:280285.
88. Sreekumar, R.,, D. L. Rasmussen,, R. H. Wiesner, and , M. R. Charlton. 2002. Differential allograft gene expression in acute cellular rejection and recurrence of hepatitis C after liver transplantation. Liver Transplant. 8:814821.
89. Stahlberg, A.,, J. Hakansson,, X. Xian,, H. Semb, and , M. Kubista. 2004. Properties of the reverse transcription reaction in mRNA quantification. Clin. Chem. 50:509515.
90. Strehlau, J.,, M. Pavlakis,, M. Lipman,, M. Shapiro,, L. Vasconcellos,, W. Harmon, and , T. B. Strom. 1997. Quantitative detection of immune activation transcripts as a diagnostic tool in kidney transplantation. Proc. Natl. Acad. Sci. USA 94:695700.
91. Suthanthiran, M. 1998. Human renal allograft rejection: molecular characterization. Nephrol. Dial. Transplant. 13:(Suppl. 1):2124.
92. Suthanthiran, M., and , T. B. Strom. 1994. Renal transplantation. N. Engl. J. Med. 331:365376.
93. Tan, L.,, W. M. Howell,, J. L. Smith, and , S. A. Sadek. 2001. Sequential monitoring of peripheral T-lymphocyte cytokine gene expression in the early post renal allograft period. Transplantation 71:751759.
94. Tatapudi, R. R.,, T. Muthukumar,, D. Dadhania,, R. Ding,, B. Li,, V. K. Sharma,, E. Lozada-Pastorio,, N. Seetharamu,, C. Hartono,, D. Serur,, S. V. Seshan,, S. Kapur,, W. W. Hancock, and , M. Suthanthiran. 2004. Noninvasive detection of renal allograft inflammation by measurements of mRNA for IP-10 and CXCR3 in urine. Kidney Int. 65:23902397.
95. Utans, U.,, R. J. Arceci,, Y. Yamashita, and , M. E. Russell. 1995. Cloning and characterization of allograft inflammatory factor-1: a novel macrophage factor identified in rat cardiac allografts with chronic rejection. J. Clin. Investig. 95:29542962.
96. Van der Leij, J.,, A. Van den Berg,, E. W J. A. Albrecht,, T. Blokzijl,, R. Roozendaal,, A. S. H. Gouw,, K. P. De Jong,, C. A. Stegeman,, H. Van Goor,, N. S. Chang, and , S. Poppema. 2003. High expression of TIAF-1 in chronic kidney and liver allograft rejection and in activated T-helper cells. Transplantation 75:20762082.
97. Vasconcellos, L. M.,, A. D. Schachter,, X. X. Zheng,, L. H. Vasconcellos,, M. Shapiro,, W. E. Harmon, and , T. B. Strom. 1998. Cytotoxic lymphocyte gene expression in peripheral blood leukocytes correlates with rejecting renal allografts. Transplantation 66:562566.
98. Velculescu, V. E.,, L. Zhang,, B. Vogelstein, and , K. W. Kinzler. 1995. Serial analysis of gene expression. Science 270:484487.
99. Wiesner, R. H.,, K. P. Batts, and , R. A. Krom. 1999. Evolving concepts in the diagnosis, pathogenesis, and treatment of chronic hepatic allograft rejection. Liver Transpl. Surg. 5:388400.
100. Xu, G. P.,, V K. Sharma,, B. Li,, R. Bologa,, Y. Li,, J. Mouradian,, J. Wang,, D. Serur,, V. Rao, and , K. H. Stenzel. 1995. Intragraft expression of IL-10 messenger RNA: a novel correlate of renal allograft rejection. Kidney Int. 48:15041507.
101. Yamada, S.,, K. Shinozaki, and , K. Agematsu. 2002. Involvement of CD27/CD70 interactions in antigen-specific cytotoxic T-lymphocyte (CTL) activity by perforin-mediated cytotoxicity. Clin. Exp. Immunol. 130:424430.
102. Yamani, M. H.,, J. Yang,, C. S. Masri,, N. B. Ratliff,, M. Bond,, R. C. Starling,, P. McCarthy,, E. Plow, and , J. B. Young. 2002. Acute cellular rejection following human heart transplantation is associated with increased expression of vitronectin receptor (integrin av(33). Am. J. Transplant. 2:129133.
103. Yang, J. W., and , Y. H. Liu. 2002. Blockage of tubular epithelial to myofibroblast transition by hepatocyte growth factor prevents renal interstitial fibrosis. J. Am. Soc. Nephrol. 13:96107.
104. Yousem, S. A.,, G. J. Berry,, P. T. Cagle,, D. Chamberlain,, A. N. Husain,, R. H. Hruban,, A. Marchevsky,, N. P. Ohori,, J. Ritter,, S. Stewart, and , H. D. Tazelaar. 1996. Revision of the 1990 working formulation for the classification of pulmonary allograft rejection: Lung Rejection Study Group. J. Heart Lung Transplant. 15:115.
105. Zeisberg, M.,, J. I. Hanai,, H. Sugimoto,, T. Mammoto,, D. Charytan,, F. Strutz, and , R. Kalluri. 2003. BMP-7 counteracts TGF- β1-induced epithelial-to-mesenchymal transition and reverse chronic renal injury. Nat. Med. 9:964968.
106. Zhang, W.,, I. Shmulevich, and , J. Astola. 2004. Microarray Quality Control. John Wiley & Sons, Hoboken, N.J.
107. Zhao, X. M.,, H. Yenya,, G. G. Miller,, A. D. Luster,, R. N. Mitchell, and , P. Libby. 2002. Differential expression of the IFN-7-inducible CXCR3-binding chemokines, IFN-inducible protein 10, monokine induced by IFN, and IFN-inducible T cell α chemoattractant in human cardiac allografts: association with cardiac allograft vasculopathy and acute rejection. J. Immunol. 169:15561560.
108. Zhao, X. M.,, H. Yenya,, G. G. Miller,, R. N. Mitchell, and , P. Libby. 2001. Association of thrombospondin-1 and cardiac allograft vasculopathy in human cardiac allografts. Circulation 103:525531.

Tables

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TABLE 1

Noninvasive diagnosis of acute rejection of allografts

Citation: Hartono C, Dadhania D, Suthanthiran M. 2006. Molecular Characterization of Rejection in Solid Organ Transplantation, p 1244-1259. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch139

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