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OR18 C3D-Binding de novo donor-specific HLA antibodies and antibody-mediated rejection of kidney transplants
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OR18
Abstracts / Human Immunology 76 (2015) 1–37
C3D-BINDING DE NOVO DONOR-SPECIFIC HLA ANTIBODIES AND ANTIBODY-MEDIATED REJECTION OF KIDNEY TRANSPLANTS. Dessislava Kopchaliiska 1, Manpreet Singh 2, Owen Buenaventura 1, Vasishta Tatapudi 2, Stephen Tomlanovich 2, Raja Rajalingam 1. 1 Immunogenetics and Transplantation Laboratory, University of California San Francisco, San Francisco, CA, United States ; 2 Division of Nephrology, Kidney Transplant Service, University of California San Francisco, San Francisco, CA, United States. Aim: Antibody-mediated rejection (AMR) is a major cause of kidney graft loss, yet assessment of individual risk at diagnosis is impeded by the lack of a reliable prognosis assay. Here, we tested whether the capacity of HLA antibodies to bind complement component C3d allows accurate risk stratification at the time of AMR diagnosis. Methods: Sera from kidney transplant recipients, who underwent a protocol or for-cause kidney biopsy and had detectable de novo DSA (by One Lambda) at the time of biopsy (median 3.8 yrs post-tx), were included in this study. These serum samples were re-tested using the Immucor single antigen beads with and without C3d detection system. Results: This study included samples from 123 kidney recipients (70 males; 14 re-Tx; 46 LD) transplanted in our center between 1989 and 2011. Fifty-seven patients (46%) had C3d-binding DSA. Most C3d-binding DSAs were high MFI DSAs (11700 + 5188), and only 4/57 (7%) C3d-binding DSAs had <5000 MFI. Seventy percent of the patients with C3d-binding DSA (40/57) had AMR (18 aAMR and 22 cAMR) and C4d-positive biopsies; twenty-six percent (15/57) had ACR, and four percent (2/57) had negative biopsies. Fifty-two present of the patients (34/66) in the C3d-negative DSA group had DSA with MFI<5000. Some of the weak and moderate DSA detected by One Lambda single antigen bead reagents were not detected with the Immucor SAB. Among the patients with C3d-negative DSA, thirty-five percent (23/66) had AMR (7 aAMR and 16 cAMR); twelve percent (8/66) had ACR and thirty-three percent (22/66) had C4d-positive biopsies. In most cases 15/22 (68%), the C4d-positive biopsies were observed in patients with strong DSA (MFI>5000). Conclusions: Our data indicate a strong correlation between the presence of C3d-binding DSAs and AMR. C3d-binding antibodies seem to be prevalent to stronger antibodies. Further studies are needed to evaluate whether the presence of C3d-binding donor-specific antibodies can predict AMR and identify patients who are at increased risk of allograft failure.
OR18
Abstracts / Human Immunology 76 (2015) 1–37
C3D-BINDING DE NOVO DONOR-SPECIFIC HLA ANTIBODIES AND ANTIBODY-MEDIATED REJECTION OF KIDNEY TRANSPLANTS. Dessislava Kopchaliiska 1, Manpreet Singh 2, Owen Buenaventura 1, Vasishta Tatapudi 2, Stephen Tomlanovich 2, Raja Rajalingam 1. 1 Immunogenetics and Transplantation Laboratory, University of California San Francisco, San Francisco, CA, United States ; 2 Division of Nephrology, Kidney Transplant Service, University of California San Francisco, San Francisco, CA, United States. Aim: Antibody-mediated rejection (AMR) is a major cause of kidney graft loss, yet assessment of individual risk at diagnosis is impeded by the lack of a reliable prognosis assay. Here, we tested whether the capacity of HLA antibodies to bind complement component C3d allows accurate risk stratification at the time of AMR diagnosis. Methods: Sera from kidney transplant recipients, who underwent a protocol or for-cause kidney biopsy and had detectable de novo DSA (by One Lambda) at the time of biopsy (median 3.8 yrs post-tx), were included in this study. These serum samples were re-tested using the Immucor single antigen beads with and without C3d detection system. Results: This study included samples from 123 kidney recipients (70 males; 14 re-Tx; 46 LD) transplanted in our center between 1989 and 2011. Fifty-seven patients (46%) had C3d-binding DSA. Most C3d-binding DSAs were high MFI DSAs (11700 + 5188), and only 4/57 (7%) C3d-binding DSAs had <5000 MFI. Seventy percent of the patients with C3d-binding DSA (40/57) had AMR (18 aAMR and 22 cAMR) and C4d-positive biopsies; twenty-six percent (15/57) had ACR, and four percent (2/57) had negative biopsies. Fifty-two present of the patients (34/66) in the C3d-negative DSA group had DSA with MFI<5000. Some of the weak and moderate DSA detected by One Lambda single antigen bead reagents were not detected with the Immucor SAB. Among the patients with C3d-negative DSA, thirty-five percent (23/66) had AMR (7 aAMR and 16 cAMR); twelve percent (8/66) had ACR and thirty-three percent (22/66) had C4d-positive biopsies. In most cases 15/22 (68%), the C4d-positive biopsies were observed in patients with strong DSA (MFI>5000). Conclusions: Our data indicate a strong correlation between the presence of C3d-binding DSAs and AMR. C3d-binding antibodies seem to be prevalent to stronger antibodies. Further studies are needed to evaluate whether the presence of C3d-binding donor-specific antibodies can predict AMR and identify patients who are at increased risk of allograft failure.