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HLA identical kidney transplant recipients who reject grafts have high incidences of antibodies to endothelial cells and MICA
S86
1.1 133-P
Abstracts
HLA IDENTICAL KIDNEY TRANSPLANT RECIPIENTS WHO REJECT GRAFTS HAVE HIGH INCIDENCES OF ANTIBODIES TO ENDOTHELIAL CELLS AND MICA K. Mizutani,1 R.N.J. Shih,2 R. Pei,2 J. Lee,2 M. Ozawa,2 A. Rosen,3 V. Esquenazi,3 J. Miller,3 P. Terasaki1, 1Terasaki Foundation Laboratory, Los Angeles, CA, USA; 2One Lambda, Inc., Canoga Park, CA, USA; 3Surgery, Miami University School of Medicine, Miami, FL, USA Purpose: Since approximately 30% of HLA identical sibling donor kidney transplants are rejected in 10 years, we examined the sera of patients with HLA identical sibling donor transplants for antibodies (abs) against endothelial cells and MICA. Methods: The sera of 13 patients who rejected HLA identical sibling donor transplants were compared against sera of 51 patients with functioning transplants from HLA identical donors. HLA abs were first examined against IgG Class I & II. Sera not having HLA abs were tested by cytotoxicity against 12 endothelial cell lines and MICA recombinant cell lines: 002, 004, 007,008,012,017, and 018. Results: 23% of patients who rejected a transplant had HLA abs, compared to 29% of those with functioning kidneys. Among the HLA negative patients, 80% with a rejected transplant had MICA abs, compared to 39% of those with a functioning graft (p⬍ 0.05). Also, 30% of rejected transplant had abs to endothelial cells, compared to 22% of those with a functioning graft (N.S.). However, in the rejected group, 90% were positive to endothelial cells and/or MICA lines, compared to 50 % in the functioning group (p⬍0.05). Conclusion: MICA and endothelial cell abs may be responsible for rejection of HLA identical sibling donor grafts.
Authors from One Lambda had supplied the antibody testing kit for tests.
1.1 134-P
HUMORAL RESPONSES TO RENAL ALLOGRAFTS ARE NOT ALWAYS DONOR-SPECIFIC Quanzong Mao, Paul I. Terasaki, Constanze Schonemann, Junchao Cai, Terasaki Foundation Laboratory, TFL, Los Angeles, CA, USA It has become apparent that humoral responses to renal allografts often are not donor specific antibodies (DSA). We confirmed this finding in 50 kidney transplant patients by testing with single antigen luminex beads for Class I and single antigen flow cytometry beads for Class II. As the table shows, among 50 patients, 100% had anti-HLA antibodies, and 46% were DSA positive. Class I antibodies were found in 99.2% of patients with a primary graft, of which 22.2% were against DSA. However, in the regraft group, they were found in 100% of the patients in which 85.7% were against DSA. Class II antibodies were found in 63.8%, 13.9% of which were against DSA in the primary group. In the regraft group, 78.5% were positive, 42.8% of which were against DSA. This data shows that in addition to DSA, non-donor specific antibodies often appear in response to kidney transplants. It is important to note that all patients who had antibodies to DSA also had antibodies which were NOT against DSA. We conclude that the humoral response to an allograft is usually a broad response, which includes antibodies to DSA in 46 %, but does not have antibodies to DSA in 54%. TABLE 1: Example of QSE Tool The Detection of Anti-HLA Antibodies Class I Class II group number NDSA ⫹ DSA ⫹ NDSA ⫹ DSA ⫹ primary 36 75% 22.2% 50% 13.9% regraft 14 14.3% 85.7%to1stD 37.5% 28.6%to1stD 21.4%to2ndD 28.6%to2ndD total 50 58% 40% 26% 22% 1stD first donor; 2ndD second donor
Class I/Class II NDSA ⫹ DSA ⫹ 69.5% 30.5% 14.3% 85.7% 54%
46%
1.1 133-P
Abstracts
HLA IDENTICAL KIDNEY TRANSPLANT RECIPIENTS WHO REJECT GRAFTS HAVE HIGH INCIDENCES OF ANTIBODIES TO ENDOTHELIAL CELLS AND MICA K. Mizutani,1 R.N.J. Shih,2 R. Pei,2 J. Lee,2 M. Ozawa,2 A. Rosen,3 V. Esquenazi,3 J. Miller,3 P. Terasaki1, 1Terasaki Foundation Laboratory, Los Angeles, CA, USA; 2One Lambda, Inc., Canoga Park, CA, USA; 3Surgery, Miami University School of Medicine, Miami, FL, USA Purpose: Since approximately 30% of HLA identical sibling donor kidney transplants are rejected in 10 years, we examined the sera of patients with HLA identical sibling donor transplants for antibodies (abs) against endothelial cells and MICA. Methods: The sera of 13 patients who rejected HLA identical sibling donor transplants were compared against sera of 51 patients with functioning transplants from HLA identical donors. HLA abs were first examined against IgG Class I & II. Sera not having HLA abs were tested by cytotoxicity against 12 endothelial cell lines and MICA recombinant cell lines: 002, 004, 007,008,012,017, and 018. Results: 23% of patients who rejected a transplant had HLA abs, compared to 29% of those with functioning kidneys. Among the HLA negative patients, 80% with a rejected transplant had MICA abs, compared to 39% of those with a functioning graft (p⬍ 0.05). Also, 30% of rejected transplant had abs to endothelial cells, compared to 22% of those with a functioning graft (N.S.). However, in the rejected group, 90% were positive to endothelial cells and/or MICA lines, compared to 50 % in the functioning group (p⬍0.05). Conclusion: MICA and endothelial cell abs may be responsible for rejection of HLA identical sibling donor grafts.
Authors from One Lambda had supplied the antibody testing kit for tests.
1.1 134-P
HUMORAL RESPONSES TO RENAL ALLOGRAFTS ARE NOT ALWAYS DONOR-SPECIFIC Quanzong Mao, Paul I. Terasaki, Constanze Schonemann, Junchao Cai, Terasaki Foundation Laboratory, TFL, Los Angeles, CA, USA It has become apparent that humoral responses to renal allografts often are not donor specific antibodies (DSA). We confirmed this finding in 50 kidney transplant patients by testing with single antigen luminex beads for Class I and single antigen flow cytometry beads for Class II. As the table shows, among 50 patients, 100% had anti-HLA antibodies, and 46% were DSA positive. Class I antibodies were found in 99.2% of patients with a primary graft, of which 22.2% were against DSA. However, in the regraft group, they were found in 100% of the patients in which 85.7% were against DSA. Class II antibodies were found in 63.8%, 13.9% of which were against DSA in the primary group. In the regraft group, 78.5% were positive, 42.8% of which were against DSA. This data shows that in addition to DSA, non-donor specific antibodies often appear in response to kidney transplants. It is important to note that all patients who had antibodies to DSA also had antibodies which were NOT against DSA. We conclude that the humoral response to an allograft is usually a broad response, which includes antibodies to DSA in 46 %, but does not have antibodies to DSA in 54%. TABLE 1: Example of QSE Tool The Detection of Anti-HLA Antibodies Class I Class II group number NDSA ⫹ DSA ⫹ NDSA ⫹ DSA ⫹ primary 36 75% 22.2% 50% 13.9% regraft 14 14.3% 85.7%to1stD 37.5% 28.6%to1stD 21.4%to2ndD 28.6%to2ndD total 50 58% 40% 26% 22% 1stD first donor; 2ndD second donor
Class I/Class II NDSA ⫹ DSA ⫹ 69.5% 30.5% 14.3% 85.7% 54%
46%