Modifiers of complement activation for prevention of antibody-mediated injury to allografts

Current Opinion in Organ Transplantation

Volumn 16, Issue 4, 2011, Pages 425-433

  Hughes, Peter D ^a   Cohney, Solomon J ^a,b  

^a ROYAL MELBOURNE HOSPITAL   (Australia)

^b Western Hospital   (Australia)

Author keywords

antibody; complement; rejection; transplantation

Indexed keywords

ALTERNATIVE COMPLEMENT PATHWAY C3 C5 CONVERTASE; CLASSICAL COMPLEMENT PATHWAY C3 C5 CONVERTASE; COMPLEMENT COMPONENT C1Q; COMPLEMENT COMPONENT C1S INHIBITOR; COMPLEMENT COMPONENT C2; COMPLEMENT COMPONENT C3A; COMPLEMENT COMPONENT C4; COMPLEMENT COMPONENT C4D; COMPLEMENT COMPONENT C5A; ECULIZUMAB; FIBROBLAST GROWTH FACTOR; HLA ANTIBODY; HLA ANTIGEN CLASS 1; IMMUNOGLOBULIN; LACTATE DEHYDROGENASE; MANNAN BINDING LECTIN ASSOCIATED SERINE PROTEINASE; MANNOSE BINDING LECTIN; MENINGOCOCCUS VACCINE; MONOCYTE CHEMOTACTIC PROTEIN 1; NEUTRALIZING ANTIBODY; PLATELET DERIVED GROWTH FACTOR; TRANSFORMING GROWTH FACTOR BETA;

ANTIBODY MEDIATED REJECTION; ANTIGEN BINDING; APOPTOSIS; BLOOD GROUP ABO INCOMPATIBILITY; BLOOD VESSEL PERMEABILITY; BRONCHIOLITIS; CELL ACTIVATION; CELL PROLIFERATION; CHEMOTAXIS; COMPLEMENT ACTIVATION; CROSS REACTION; DRUG BINDING; ENDOTHELIUM CELL; GLOMERULOPATHY; GRAFT FAILURE; GRAFT REJECTION; HEART TRANSPLANTATION; HUMAN; IMMUNOADSORPTION; KALLIKREIN KININ SYSTEM; KIDNEY TRANSPLANTATION; LACTATE DEHYDROGENASE BLOOD LEVEL; LIVER TRANSPLANTATION; LUNG LAVAGE; NONHUMAN; ORGAN DONOR; PAROXYSMAL NOCTURNAL HEMOGLOBINURIA; PHAGOCYTOSIS; PLASMAPHERESIS; REVIEW; THROMBOTIC THROMBOCYTOPENIC PURPURA; TRANSPLANT GLOMERULOPATHY;

ANIMALS; COMPLEMENT ACTIVATION; COMPLEMENT C4B; GRAFT REJECTION; GRAFT SURVIVAL; HISTOCOMPATIBILITY; HLA ANTIGENS; HUMANS; IMMUNOLOGIC FACTORS; ISOANTIBODIES; ORGAN TRANSPLANTATION; PEPTIDE FRAGMENTS; TRANSPLANTATION TOLERANCE; TRANSPLANTATION, HOMOLOGOUS; TREATMENT OUTCOME;

EID: 80051755699     PISSN: 10872418     EISSN: 15317013     Source Type: Journal    
DOI: 10.1097/MOT.0b013e3283489a5a     Document Type: Review

References (121)

1. Pilmore H, Dent H, Chang S, et al. Reduction in cardiovascular death after kidney transplantation. Transplantation 2010; 89:851-857.
2. Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: A key system for immune surveillance and homeostasis. Nat Immunol 2010; 11:785-797. Comprehensive and excellent review of complement biology and function including recent developments in the field.
3. Zhang X, Reed EF. Effect of antibodies on endothelium. Am J Transplant 2009; 9:2459-2465. A thorough review of potential outcomes following antibody binding to endothelium, and theoretical discussion of the determinants of rejection, graft acceptance and accommodation.
4. Wasowska BA. Mechanisms involved in antibody-and complementmediated allograft rejection. Immunol Res 2010; 47 (1-3):25-44.
5. Colvin RB, Smith RN. Antibody-mediated organ-allograft rejection. Nat Rev Immunol 2005; 5:807-817. (Pubitemid 41400854)
6. Selvan RS, Kapadia HB, Platt JL. Complement-induced expression of chemokine genes in endothelium: Regulation by IL-1-dependent and -independent mechanisms. J Immunol 1998; 161:4388-4395. (Pubitemid 28469025)
7. Kilgore KS, Shen JP, Miller BF, et al. Enhancement by the complement membrane attack complex of tumor necrosis factor-alpha-induced endothelial cell expression of E-selectin and ICAM-1. J Immunol 1995; 155:1434-1441.
8. Kilgore KS, Schmid E, Shanley TP, et al. Sublytic concentrations of the membrane attack complex of complement induce endothelial interleukin-8 and monocyte chemoattractant protein-1 through nuclear factor-kappa B activation. Am J Pathol 1997; 150:2019-2031. (Pubitemid 27233075)
9. Kumar V, Ali SR, Konrad S, et al. Cell-derived anaphylatoxins as key mediators of antibody-dependent type II autoimmunity in mice. J Clin Invest 2006; 116:512-520. (Pubitemid 43228369)
10. Nimmerjahn F, Ravetch JV. Fcgamma receptors as regulators of immune responses. Nat Rev Immunol 2008; 8:34-47.
11. Pratt JR, Basheer SA, Sacks SH. Local synthesis of complement component C3 regulates acute renal transplant rejection. Nat Med 2002; 8:582-587. (Pubitemid 34633435)
12. Heeger PS, Lalli PN, Lin F, et al. Decay-accelerating factor modulates induction of T cell immunity. J Exp Med 2005; 201:1523-1530. (Pubitemid 40720998)
13. Kim AH, Dimitriou ID, Holland MC, et al. Complement C5a receptor is essential for the optimal generation of antiviral CD8+ T cell responses. J Immunol 2004; 173:2524-2529. (Pubitemid 39063111)
14. Dempsey PW, Allison ME, Akkaraju S, et al. C3d of complement as a molecular adjuvant: Bridging innate and acquired immunity. Science 1996; 271:348-350.
15. Botto M, Walport MJ. C1q, autoimmunity and apoptosis. Immunobiology 2002; 205 (4-5):395-406. (Pubitemid 35153956)
16. Csencsits K, Burrell BE, Lu G, et al. The classical complement pathway in transplantation: Unanticipated protective effects of C1q and role in inductive antibody therapy. Am J Transplant 2008; 8:1622-1630.
17. Hellerud BC, Aase A, Herstad TK, et al. Critical roles of complement and antibodies in host defense mechanisms against Neisseria meningitidis as revealed by human complement genetic deficiencies. Infect Immun 2010; 78:802-809.
18. Lappegard KT, Christiansen D, Pharo A, et al. Human genetic deficiencies reveal the roles of complement in the inflammatory network: Lessons from nature. Proc Natl Acad Sci U S A 2009; 106:15861-15866.
19. Davis AE 3rd. The pathophysiology of hereditary angioedema. Clin Immunol 2005; 114:3-9. (Pubitemid 39646476)
20. Hill A, Richards SJ, Hillmen P. Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria. Br J Haematol 2007; 137:181-192. (Pubitemid 46537635)
21. Kavanagh D, Richards A, Atkinson J. Complement regulatory genes and hemolytic uremic syndromes. Annu Rev Med 2008; 59:293-309. (Pubitemid 351287939)
22. Noris M, Remuzzi G. Thrombotic microangiopathy after kidney transplantation. Am J Transplant 2010; 10:1517-1523.
23. Worthley DL, Johnson DF, Eisen DP, et al. Donor mannose-binding lectin deficiency increases the likelihood of clinically significant infection after liver transplantation. Clin Infect Dis 2009; 48:410-417.
24. Carroll KE, Dean MM, Heatley SL, et al. High levels of mannose-binding lectin are associated with poor outcomes after lung transplantation. Transplantation 2011; 91:1044-1049.
25. Berger SP, Roos A, Mallat MJ, et al. Association between mannose-binding lectin levels and graft survival in kidney transplantation. Am J Transplant 2005; 5:1361-1366. (Pubitemid 40839426)
26. Bian H, Reed EF. Alloantibody-mediated class I signal transduction in endothelial cells and smooth muscle cells: Enhancement by IFN-gamma and TNF-alpha. J Immunol 1999; 163:1010-1018. (Pubitemid 29328114)
27. Smith JD, Lawson C, Yacoub MH, Rose ML. Activation of NF-kappa B in human endothelial cells induced by monoclonal and allospecific HLA antibodies. Int Immunol 2000; 12:563-571. (Pubitemid 30199362)
28. Jin YP, Jindra PT, Gong KW, et al. Anti-HLA class I antibodies activate endothelial cells and promote chronic rejection. Transplantation 2005; 79 (3 Suppl):S19-S21. (Pubitemid 40293567)
29. Jin YP, Singh RP, Du ZY, et al. Ligation of HLA class I molecules on endothelial cells induces phosphorylation of Src, paxillin, and focal adhesion kinase in an actin-dependent manner. J Immunol 2002; 168:5415-5423. (Pubitemid 34556118)
30. Rahimi S, Qian Z, Layton J, et al. Noncomplement-and complement- activating antibodies synergize to cause rejection of cardiac allografts. Am J Transplant 2004; 4:326-334. (Pubitemid 38282287)
31. Wasowska BA, Qian Z, Cangello DL, et al. Passive transfer of alloantibodies restores acute cardiac rejection in IgKO mice. Transplantation 2001; 71:727-736. (Pubitemid 32377270)
32. Yamakuchi M, Kirkiles-Smith NC, Ferlito M, et al. Antibody to human leukocyte antigen triggers endothelial exocytosis. Proc Natl Acad Sci U S A 2007; 104:1301-1306. (Pubitemid 46183999)
33. Murata K, Fox-Talbot K, Qian Z, et al. Synergistic deposition of C4d by complement-activating and nonactivating antibodies in cardiac transplants. Am J Transplant 2007; 7:2605-2614. (Pubitemid 47561614)
34. Feucht HE. Complement C4d in graft capillaries: The missing link in the recognition of humoral alloreactivity. Am J Transplant 2003; 3:646-652. (Pubitemid 36745236)
35. Feucht HE, Felber E, Gokel MJ, et al. Vascular deposition of complement-split products in kidney allografts with cell-mediated rejection. Clin Exp Immunol 1991; 86:464-470.
36. Feucht HE, Schneeberger H, Hillebrand G, et al. Capillary deposition of C4d complement fragment and early renal graft loss. Kidney Int 1993; 43:1333-1338. (Pubitemid 23161421)
37. Bohmig GA, Exner M, Habicht A, et al. Capillary C4d deposition in kidney allografts: A specific marker of alloantibody-dependent graft injury. J Am Soc Nephrol 2002; 13:1091-1099. (Pubitemid 34274108)
38. Herzenberg AM, Gill JS, Djurdjev O, Magil AB. C4d deposition in acute rejection: An independent long-term prognostic factor. J Am Soc Nephrol 2002; 13:234-241. (Pubitemid 34042033)
39. Nickeleit V, Zeiler M, Gudat F, et al. Detection of the complement degradation product C4d in renal allografts: Diagnostic and therapeutic implications. J Am Soc Nephrol 2002; 13:242-251. (Pubitemid 34042034)
40. Regele H, Exner M, Watschinger B, et al. Endothelial C4d deposition is associated with inferior kidney allograft outcome independently of cellular rejection. Nephrol Dial Transplant 2001; 16:2058-2066. (Pubitemid 32970570)
41. Regele H, Bohmig GA, Habicht A, et al. Capillary deposition of complement split product C4d in renal allografts is associated with basement membrane injury in peritubular and glomerular capillaries: A contribution of humoral immunity to chronic allograft rejection. J Am Soc Nephrol 2002; 13:2371-2380. (Pubitemid 34925248)
42. Collins AB, Schneeberger EE, Pascual MA, et al. Complement activation in acute humoral renal allograft rejection: Diagnostic significance of C4d deposits in peritubular capillaries. J Am Soc Nephrol 1999; 10:2208-2214. (Pubitemid 29453499)
43. Haas M. The significance of C4d staining with minimal histologic abnormalities. Curr Opin Organ Transplant 2010; 15:21-27.
44. Lynch RJ, Platt JL. Escaping from rejection. Transplantation 2009; 88:1233-1236. Interesting and concise article discussing mechanisms of transplant acceptance and accomodation.
45. Flint SM, Walker RG, Hogan C, et al. Successful ABO-incompatible kidney transplantation with antibody removal and standard immunosuppression. Am J Transplant 2011; 11:1016-1024.
46. Cohney S, Flint SM, Hughes P, et al. Successful ABO-incompatible renal transplantation with conventional immunosuppression alone: No splenectomy, no rituximab & no antibody removal [abstract]. Am J Transplant 2009; 9 (Suppl s2):220.
47. Breimer ME, Rydberg L, Jackson AM, et al. Multicenter evaluation of a novel endothelial cell crossmatch test in kidney transplantation. Transplantation 2009; 87:549-556.
48. Fredrich R, Toyoda M, Czer LS, et al. The clinical significance of antibodies to human vascular endothelial cells after cardiac transplantation. Transplantation 1999; 67:385-391. (Pubitemid 29094008)
49. Satoskar AA, Pelletier R, Adams P, et al. De novo thrombotic microangiopathy in renal allograft biopsies-role of antibody-mediated rejection. Am J Transplant 2010; 10:1804-1811.
50. Meehan SM, Kremer J, Ali FN, et al. Thrombotic microangiopathy and peritubular capillary C4d expression in renal allograft biopsies. Clin J Am Soc Nephrol 2011; 6:395-403.
51. Batal I, Zainah H, Stockhausen S, et al. The significance of renal C4d staining in patients with BK viruria, viremia, and nephropathy. Mod Pathol 2009; 22:1468-1476.
52. Vallhonrat H, Williams WW, Cosimi AB, et al. In vivo generation of C4d, Bb, iC3b, and SC5b-9 after OKT3 administration in kidney and lung transplant recipients. Transplantation 1999; 67:253-258. (Pubitemid 29066350)
53. Baldwin WM 3rd, Armstrong LP, Samaniego-Picota M, et al. Antithymocyte globulin is associated with complement deposition in cardiac transplant biopsies. Hum Immunol 2004; 65:1273-1280. (Pubitemid 39535290)
54. Troxell ML, Higgins JP, Kambham N. Evaluation of C4d staining in liver and small intestine allografts. Arch Pathol Lab Med 2006; 130:1489-1496. (Pubitemid 44520715)
55. Takemoto SK, Zeevi A, Feng S, et al. National conference to assess antibodymediated rejection in solid organ transplantation. Am J Transplant 2004; 4:1033-1041. (Pubitemid 38868592)
56. Smith RN, Brousaides N, Grazette L, et al. C4d deposition in cardiac allografts correlates with alloantibody. J Heart Lung Transplant 2005; 24:1202-1210. (Pubitemid 41247799)
57. Kucirka LM, Maleszewski JJ, Segev DL, Halushka MK. Survey of North American pathologist practices regarding antibody-mediated rejection in cardiac transplant biopsies. Cardiovasc Pathol 2011; 20:132-138.
58. Murata K, Baldwin WM 3rd. Mechanisms of complement activation, C4d deposition, and their contribution to the pathogenesis of antibody-mediated rejection. Transplant Rev (Orlando) 2009; 23:139-150.
59. Magro CM, Klinger DM, Adams PW, et al. Evidence that humoral allograft rejection in lung transplant patients is not histocompatibility antigen-related. Am J Transplant 2003; 3:1264-1272. (Pubitemid 37214623)
60. Miller GG, Destarac L, Zeevi A, et al. Acute humoral rejection of human lung allografts and elevation of C4d in bronchoalveolar lavage fluid. Am J Transplant 2004; 4:1323-1330. (Pubitemid 39013580)
61. Olausson M, Mjornstedt L, Norden G, et al. Successful combined partial auxiliary liver and kidney transplantation in highly sensitized cross-match positive recipients. Am J Transplant 2007; 7:130-136. (Pubitemid 44952865)
62. Baan CC, Weimar W. How does auxiliary liver transplantation regulate alloreactivity in sensitized kidney transplant patients? Transplantation 2011; 91:823-824.
63. Haga H, Egawa H, Fujimoto Y, et al. Acute humoral rejection and C4d immunostaining in ABO blood type-incompatible liver transplantation. Liver Transpl 2006; 12:457-464.
64. Kozlowski T, Rubinas T, Nickeleit V, et al. Liver allograft antibody-mediated rejection with demonstration of sinusoidal C4d staining and circulating donor-specific antibodies. Liver Transpl 2011; 17:357-368.
65. Prikis M, Norman D, Rayhill S, et al. Preserved endocrine function in a pancreas transplant recipient with pancreatic panniculitis and antibodymediated rejection. Am J Transplant 2010; 10:2717-2722.
66. de Kort H, Munivenkatappa RB, Berger SP, et al. Pancreas allograft biopsies with positive c4d staining and antidonor antibodies related to worse outcome for patients. Am J Transplant 2010; 10:1660-1667.
67. Troxell ML, Koslin DB, Norman D, et al. Pancreas allograft rejection: Analysis of concurrent renal allograft biopsies and post-therapy follow-up biopsies. Transplantation 2010; 90:75-84.
68. Heidenreich S, Junker R, Wolters H, et al. Outcome of kidney transplantation in patients with inherited thrombophilia: Data of a prospective study. J Am Soc Nephrol 2003; 14:234-239. (Pubitemid 36026314)
69. Heidenreich S, Dercken C, August C, et al. High rate of acute rejections in renal allograft recipients with thrombophilic risk factors. J Am Soc Nephrol 1998; 9:1309-1313. (Pubitemid 28283896)
70. Gloor J, Stegall MD. Sensitized renal transplant recipients: Current protocols and future directions. Nat Rev Nephrol 2010; 6:297-306. Recent and comprehensive review of management approaches for overcoming HLA antibodies and antibody-mediated rejection in renal transplant recipients.
71. Li K, Sacks SH, Zhou W. The relative importance of local and systemic complement production in ischaemia, transplantation and other pathologies. Mol Immunol 2007; 44:3866-3874. (Pubitemid 47332623)
72. Tang S, Zhou W, Sheerin NS, et al. Contribution of renal secreted complement C3 to the circulating pool in humans. J Immunol 1999; 162:4336-4341. (Pubitemid 29314826)
73. Zhou W, Medof ME, Heeger PS, Sacks S. Graft-derived complement as a mediator of transplant injury. Curr Opin Immunol 2007; 19:569-576. (Pubitemid 47464917)
74. Jordan SC, Toyoda M, Kahwaji J, Vo AA. Clinical aspects of intravenous immunoglobulin use in solid organ transplant recipients. Am J Transplant 2011; 11:196-202. A detailed review of the use of IVIg for transplanting patients with pre-existing HLA-antibodies and for the treatment of antibody-mediated rejection.
75. Shehata N, Palda VA, Meyer RM, et al. The use of immunoglobulin therapy for patients undergoing solid organ transplantation: An evidence-based practice guideline. Transfus Med Rev 2010; 24 (Suppl 1):S7-S27.
76. Nahirniak S, Hume HA. Guidelines for the use of immunoglobulin therapy for primary immune deficiency and solid organ transplantation. Transfus Med Rev 2010; 24 (Suppl 1):S1-S6.
77. Jordan SC, Reinsmoen N, Peng A, et al. Advances in diagnosing and managing antibody-mediated rejection. Pediatr Nephrol 2010; 25:2035-2045; quiz 45-48. Thorough and detailed review of clinical aspects of managing sensitized renal transplant recipients and antibody-mediated rejection.
78. Zachary AA, Montgomery RA, Leffell MS. Factors associated with and predictive of persistence of donor-specific antibody after treatment with plasmapheresis and intravenous immunoglobulin. Hum Immunol 2005; 66:364-370. (Pubitemid 40615791)
79. Tobian AA, Shirey RS, Montgomery RA, et al. The critical role of plasmapheresis in ABO-incompatible renal transplantation. Transfusion 2008; 48:2453-2460.
80. Zachary AA, Montgomery RA, Ratner LE, et al. Specific and durable elimination of antibody to donor HLA antigens in renal-transplant patients. Transplantation 2003; 76:1519-1525. (Pubitemid 37467706)
81. Stegall MD, Diwan TS, Cornell LD, et al. Terminal complement inhibition decreases early acute humoral rejection in sensitized renal transplant recipients. Am J Transplant 2010; 10 (Suppl s4):39.
82. Wood L, Jacobs P. The effect of serial therapeutic plasmapheresis on platelet count, coagulation factors, plasma immunoglobulin, and complement levels. J Clin Apher 1986; 3:124-128. (Pubitemid 16129651)
83. Volkin RL, Starz TW, Winkelstein A, et al. Changes in coagulation factors, complement, immunoglobulins, and immune complex concentrations with plasma exchange. Transfusion 1982; 22:54-58. (Pubitemid 12158912)
84. Tankersley DL, Preston MS, Finlayson JS. Immunoglobulin G dimer: An idiotype-antiidiotype complex. Mol Immunol 1988; 25:41-48.
85. Rossi F, Dietrich G, Kazatchkine MD. Antiidiotypic suppression of autoantibodies with normal polyspecific immunoglobulins. Res Immunol 1989; 140:19-31. (Pubitemid 19121896)
86. Rossi F, Dietrich G, Kazatchkine MD. Antiidiotypes against autoantibodies in normal immunoglobulins: Evidence for network regulation of human autoimmune responses. Immunol Rev 1989; 110:135-149. (Pubitemid 19216013)
87. Tyan DB, Li VA, Czer L, et al. Intravenous immunoglobulin suppression of HLA alloantibody in highly sensitized transplant candidates and transplantation with a histoincompatible organ. Transplantation 1994; 57:553-562. (Pubitemid 24075802)
88. Jordan SC, Quartel AW, Czer LS, et al. Posttransplant therapy using highdose human immunoglobulin (intravenous gammaglobulin) to control acute humoral rejection in renal and cardiac allograft recipients and potential mechanism of action. Transplantation 1998; 66:800-805.
89. Jordan SC, Tyan D, Czer L, Toyoda M. Immunomodulatory actions of intravenous immunoglobulin (IVIG): Potential applications in solid organ transplant recipients. Pediatr Transplant 1998; 2:92-105. (Pubitemid 128655513)
90. Jordan SC, Toyoda M, Vo AA. Intravenous immunoglobulin a natural regulator of immunity and inflammation. Transplantation 2009; 88:1-6.
91. Nimmerjahn F, Ravetch JV. Anti-inflammatory actions of intravenous immunoglobulin. Annu Rev Immunol 2008; 26:513-533. (Pubitemid 351600384)
92. Basta M, Van Goor F, Luccioli S, et al. F(ab)'2-mediated neutralization of C3a and C5a anaphylatoxins: A novel effector function of immunoglobulins. Nat Med 2003; 9:431-438. (Pubitemid 36460077)
93. Magee JC, Collins BH, Harland RC, et al. Immunoglobulin prevents complement-mediated hyperacute rejection in swine-to-primate xenotransplantation. J Clin Invest 1995; 96:2404-2412.
94. Ricklin D, Lambris JD. Complement-targeted therapeutics. Nat Biotechnol 2007; 25:1265-1275. (Pubitemid 350089828)
95. Kelly R, Richards S, Hillmen P, Hill A. The pathophysiology of paroxysmal nocturnal hemoglobinuria and treatment with eculizumab. Ther Clin Risk Manag 2009; 5:911-921.
96. Soliris1 US Prescribing Information, 2009.
97. Soliris1 Summary of Product Characteristics 2011.
98. Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med 2006; 355:1233-1243. (Pubitemid 44427447)
99. Locke JE, Magro CM, Singer AL, et al. The use of antibody to complement protein C5 for salvage treatment of severe antibody-mediated rejection. Am J Transplant 2009; 9:231-235.
100. Lonze BE, Dagher NN, Simpkins CE, et al. Eculizumab, bortezomib and kidney paired donation facilitate transplantation of a highly sensitized patient without vascular access. Am J Transplant 2010; 10:2154-2160.
101. Lonze BE, Singer AL, Montgomery RA. Eculizumab and renal transplantation in a patient with CAPS. N Engl J Med 2010; 362:1744-1745.
102. Gruppo RA, Rother RP. Eculizumab for congenital atypical hemolytic-uremic syndrome. N Engl J Med 2009; 360:544-546.
103. Nurnberger J, Philipp T, Witzke O, et al. Eculizumab for atypical hemolyticuremic syndrome. N Engl J Med 2009; 360:542-544.
104. Stegall MD, Diwan TS, Burns JM, et al. Prevention of acute humoral rejection with C5 inhibition. Am J Transplant 2009; 9 (Suppl s2):241.
105. Cornell LD, Gloor JM, Nasr SH, et al. Chronic humoral rejection despite C5 inhibition after positive-crossmatch kidney transplantation (+XMKTx). Am J Transplant 2010; 10 (Suppl 4):125.
106. Cohney S, Hughes P, Masterson R, et al. C5 inhibition with eculizumab to prevent antibody mediated rejection (AbMR) in patients with donor specific anti-HLA antibody (DSAb) and a positive cross match. Am J Transplant 2011; 11 (Suppl s2):483.
107. Cugno M, Zanichelli A, Foieni F, et al. C1-inhibitor deficiency and angioedema: Molecular mechanisms and clinical progress. Trends Mol Med 2009; 15:69-78.
108. Emlen W, Li W, Kirschfink M. Therapeutic complement inhibition: New developments. Semin Thromb Hemost 2010; 36:660-668.
109. Tillou X, Poirier N, Le Bas-Bernardet S, et al. Recombinant human C1-inhibitor prevents acute antibody-mediated rejection in alloimmunized baboons. Kidney Int 2010; 78:152-159. An important study describing the efficacy of a C1-inhibitor in preventing antibodymediated rejection in baboons.
110. Pharming Technologies B.V. Recombinant human C1 inhibitor for the treatment of early antibody-mediated rejection in renal transplantation [Internet]. ClinicalTrials.gov. Bethesda, MD: National Library of Medicine (US). 2000. http://clinicaltrials.gov/show/NCT01035593. NLM identifier: NCT01035593. [Accessed 1 March 2011]
111. ViroPharma. A pilot study to evaluate the use of C1 esterase inhibitor (human) in patients with acute antibody-mediated rejection [Internet]. ClinicalTrials. gov. Bethesda, MD: National Library of Medicine (US). 2000. http://clinical trials.gov/show/NCT01147302. NLM Identifier: NCT01147302. [Accessed 1 March 2011]
112. Center C-SM. Safety & efficacy of Berinert1(C1 Inhibitor) therapy to prevent rejection [Internet]. ClinicalTrials.gov. Bethesda, MD: National Library of Medicine (US). 2000. http://clinicaltrials.gov/show/NCT01134510. NLMIdentifier: NCT01134510. [Accessed 1 March 2011]
113. Davis AE 3rd, Mejia P, Lu F. Biological activities of C1 inhibitor. Mol Immunol 2008; 45:4057-4063.
114. Miyagawa S, Yamamoto A, Matsunami K, et al. Complement regulation in the GalT KO era. Xenotransplantation 2010; 17:11-25.
115. Ritis K, Doumas M, Mastellos D, et al. A novel C5a receptor-tissue factor cross-talk in neutrophils links innate immunity to coagulation pathways. J Immunol 2006; 177:4794-4802. (Pubitemid 44469814)
116. Markiewski MM, Nilsson B, Ekdahl KN, et al. Complement and coagulation: Strangers or partners in crime? Trends Immunol 2007; 28:184-192. (Pubitemid 46476881)
117. Massberg S, Grahl L, von Bruehl ML, et al. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med 2010; 16:887-896.
118. Cowan PJ, Robson SC, d'Apice AJ. Controlling coagulation dysregulation in xenotransplantation. Curr Opin Organ Transplant 2011; 16:214-221.
119. Cowan PJ, d'Apice AJ. Complement activation and coagulation in xenotransplantation. Immunol Cell Biol 2009; 87:203-208.
120. Cowan PJ, Roussel JC, d'Apice AJ. The vascular and coagulation issues in xenotransplantation. Curr Opin Organ Transplant 2009; 14:161-167.
121. Crikis S, Zhang XM, Dezfouli S, et al. Anti-inflammatory and anticoagulant effects of transgenic expression of human thrombomodulin in mice. Am J Transplant 2010; 10:242-250.