1. Am. J. Transpl 2003 3:665

3. 1969 Immediate failure Kidney recipients Patel, Terasaki, N Engl J Med 280:735, 1969 with antibodies, pos XM 24/30

4. Percent Cause of death 87888990919293949596979899000102 0 1 2 0 1 Primary Graft Failure Hyperacute Rejection 1113112 13 10 12 10 8 11 17 18 75 72 80 76 81 100 123 132 123 94 119 117 119 104 38

5. Hyperacute Rejection Percent of Hyperacute % PRATransplant No. 0 0.1 0.2 0.3 0.4 0.5 <1010-80>8012>2 43 36 23 27 9 76

6. Primary Non-function 0 1 2 3 <1010-80>8012>2 % PRATransplant No. Percent of Primary Nonfunction 706 345 164 1145 256 70

7. Graft Failure in 1 month 0 1 2 3 4 5 6 7 8 9 10 11 12 13 % PRA Transplant No. Percent of Graft Failure <1010-80>8012>2 301 1283 6341 622 1550 3744

9. Feucht, Albert, et al. Kidney Intern 43:1333-38, 1993 C4d- (N =42) C4d+ (N =43) 100 90 80 70 60 50 40 30 20 10 0 0123456789101112 Months Posttransplant Graft Survival (%) 90% 57% Biopsies within first month

10. Lederer, et al. Kidney International 59:334-341, 2001 100 75 50 25 0 0481216 C4d- (N =101) C4d+ (N =117) Years Posttransplant Cumulative Survival (%) P= 0.0001

11. Feucht, Schneeberger, et al. Kidney Int 1993: 43:1333. Lederer, Kluth-Pepper, et al. Kidney Int 2001; 59:334. Feucht, Opelz. Kidney Int 1996: 50:1464. Behr, Feucht, et al. J Heart Lung Transplant 1999; 18:904. C4d publications

12. Crespo, Pascual, et al. Transplantation 2001; 71:652. Mauiyyedi, Pelle, et al. J Am Soc Nephrol 2001; 12:574. Mauiyyedi, Colvin. Curr Opin Nephrol Hypertens 2002; 11:609. Mauiyyedi, Crespo, et al. J Am Soc Nephrol 2002; 13:779. Collins, Schneeberger, et al. J Am Soc Nephrol 1999; 10:2208.

13. Regele, Watschinger, et al. Nephrol Dial Transplant 2001; 16:2058. Bohmig, Exner, et al. J Am Soc Nephrol 2002; 13:1091. Bohmig, Exner, et al. Curr Opin Urol 2002; 12:95. Watschinger, Pascual. J Am Soc Nephrol 2002; 13:2420. Nickeleit, Zeiler, et al. J Am Soc Nephrol 2002; 13:242.

15. Review: Anti-HLA antibodies post transplant in solid organ transplantation McKenna, Takemoto, Terasaki Transplantation 69:319, 2000 American J Transplantation, June, 2003

16. El Fettouh, Cook, et al. Urology 2000; 56:369. Muller-Steinhardt, Fricke, et al. Clin Transplant 2000; 14:85. Kerman, Katz, et al. Transplant Proc 2001; 33:402. Worthington, Martin, et al. Transpl Proc 2001; 33:475. Tambur AR, Bray et al.Transplant 2000; 70:1055

17. Piazza, Poggi, et al. Transplantation 2001; 71:1106. Piazza, Borrelli, et al. Transpl Int 2000; 13:s439. Pelletier, Adams, et al. Am J Transplant 2002; 2:134. Palmer, Davis, et al. Transplantation 2002; 74:799. Lau, Palmer, et al. Ann Thorac Surg 2000; 69:1520. T

18. 54% N=24 1969, Morris 72% N=25 1981, Iwaki 82% N=122 1987, Park N=100 1995, Harmer 95% After failure or removal of graft

19. 54% N=24 1969, Morris 72% N=25 1981, Iwaki 82% N=122 1987, Park N=100 1995, Harmer 95% After failure or removal of graft

20. 54% N=24 1969, Morris 72% N=25 1981, Iwaki 82% N=122 1987, Park N=100 1995, Harmer 95% After failure or removal of graft

21. 54% N=24 1969, Morris 72% N=25 1981, Iwaki 82% N=122 1987, Park N=100 1995, Harmer 95% After failure or removal of graft

22. 24 11 96% ELISA AHG 28 16 96.4% Lazda N = 445 AHG 96% 33 N=825 at 5 centers 2001, El Awar AHG 152 Rosenberg, N = 254 El-Awar,Terasaki et al, Transpl Proc 34:2531, 2002 After failure or removal of graft

23. 5 8 12 6 4 2 11 Time to antibody Time to failure 0<6M1yr2345678yr Lee,Terasaki, Transpl 74:1192, 2002

24. 0246101214168 Class II Years Posttransplant Time to antibody Time to failure Worthington, et al. Transplantation 2003, 75:1034

25. I 0246101214168 Years Posttransplant Class I Time to antibody Time to failure Worthington, et al. Transplantation 2003, 75:1034

26. Renal allograft - Post transplant Chronic Rejection

27. To prove the role of HLA antibodies in a prospective trial, One year ago 2,551 patients with functioning transplants were tested for HLA antibodies

28. 0 20 40 60 KIDNEY 628 5026100 115 41 43 41 21 17 167 104 63 47 12 61 52 LUNG LIVER HEART 36 International transplant centers, patients tested in 2002 % HLA antibody Post-transplant

29. N 23367533536 CsA, Aza CsA, MMF FK, Aza FK, MMF 0 20 40 0.073 0.34 <0.0001 * Combination Drug No pre-tx antibody

30. 9701989920009394959692 Date of transplant in 2,551 patients 1 yr wait period Antibody 0203 No antibody

31. DirectorCountryTotalPositiveNegative Schonemann Germany 621 3/1055/516 Sada Japan 191 0/600/131 Semana France 159 2/81/151 Bow MA, USA 158 1/345/124 Neumann/ Michelon Brazil 156 1/202/136 Humar Croatia 151 4/351/116 Kidney Transplants

32. DirectorCountryTotalPositiveNegative LeforFL, USA 145 4/562/89 Piazza/ Adorno Italy 126 2/293/97 duToit/ Taljaard S.Africa 110 0/270/83 Milford/ Capenter MA, USA 107 2/326/75 McAlackPA, USA 79 1/146/65 JobimBrazil 78 0/80/70

33. DirectorCountryTotalPositiveNegative Slavcev Czech 71 1/302/41 Christiansen Australia 63 1/150/48 Polymenidis/ Skoura Greece 59 1/81/51 Stavropoulos- Giokas Greece 54 1/80/46 Mehra/ Panigrahi India 47 6/372/10 Zeevi PA, USA 42 1/131/29

34. DirectorCountryTotalPositiveNegative Crowe/Langon e TN, USA 30 0/81/22 Saidman MA, USA 24 0/40/20 Orosz/ Pelletier OH, USA 24 0/50/19 TaitAustralia 23 0/51/18 Fuggle Oxford, UK 21 1/41/17 Mahoney**/ Breggia MA, USA 9 0/20/7 Abdelnoor/ Shrayteh Lebanon 3 0/00/3

35. Deaths in a total 2551 patients followed one year 567 with antibody 1,984 without antibody 1 year later, 32 died 1.1% died 1.9% died P=0.08

36. Graft failure in a total 2551 patients followed one year 567 with antibody 1,984 without antibody 1 year later, 72 fail 2.0% fail 5.6% fail P=0.000003

37. Graft failure in patients without pre- transplant antibody 1,725 total 256 with antibody 1,469 without antibody 1 year later, 45 fail 1.9% fail 6.6% fail P=0.00001

38. The tests were done by PRA (panel reactive antibodies), but are Donor Specific antibodies found?

39. #11 Single antigen flow cytometry beads Produced by isolating antigens from recombinant lines, and adhering to beads Pei, Lee et al Transpl 2003 75:43

40. #29 A1 A2 A3 A69 A66 A29 A30 Cont A26 B38 B57 B7 B52 B27 B8 B65 Cont B55 Single antigen beads

41. XX 10 9 XX 8 7 X X X 6 5 4 3 2 1 696866343331302926242311 3 21 ID Single Antigen A-Allele Typings Serum Antibodies in patients AFTER rejection Pei, Lee et al Transpl 2003 75:43

42. XX 10 9 XX 8 7 X X X 6 5 4 3 2 1 696866343331302926242311 3 21 ID Single Antigen A-Allele Typings Serum Antibodies in patients AFTER rejection Pei, Lee et al Transpl 2003 75:43

43. 20 19 18 17 16 15 14 13 12 11 6968663331302926242311321 ID Single Antigen A-Allele Typings Serum 25 Berlin, Schonemann Recip Mism

45. HLA antibodies were found to predict chronic rejection in a prospective trial. They should therefore be useful in increasing or decreasing immunosuppression

46. Humoral Theory of Transplantation Am. J. Transpl 2003 3:665 HLA antibodies cause : Hyperacute rejection Damage by early non function Acute rejection Chronic rejection

47. Humoral Theory of Transplantation Am. J. Transpl 2003 3:665 HLA antibodies cause : Hyperacute rejection Damage by early non function Acute rejection Chronic rejection

48. Humoral Theory of Transplantation Am. J. Transpl 2003 3:665 HLA antibodies cause : Hyperacute rejection Acute rejection

49. Humoral Theory of Transplantation Am. J. Transpl 2003 3:665 HLA antibodies cause : Hyperacute rejection Acute rejection Chronic rejection

50. HLAtransplantationconference.org Los Angeles, Century Plaza Hotel Jan 31 to Feb 1, 2004