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Donor-specific HLA-DR antibodies mediated rejection in heart transplant
Abstracts
127
C-6.5 #137
DONOR-SPECIFIC HLA-DR ANTIBODIES MEDIATED REJECTION IN HEART TRANSPLANT. K Monahan, P Alivazatos, M Stone, L Dombrausky, A Nikaein. Baylor University Medical Center, Dallas, TX Long-term survival of heart allograft recipients is threatened mainly by chronic vascular rejection, which results in the development of graft atherosclerosis. Chronic rejection is dominated by the development of antibodies (Abs) to donor class I HLA antigens. In this report, we present a case of heart allograft recipient who developed anti-donor specific class II HLA Abs, donor HLA-DR-specific activated T cells and vascular endothelium injury with no pathologic sign of cellular or humoral rejection of the heart. Patient was a 53 year old female (HLA type A2,3;B18,39,DR8,13) who received a heart transplant (Tx) from a donor (HLA type A2,31 ;B8,62;DR1,3) across negative crossmatch (xm) with both donor T or B lymphocytes. Pre-Tx Panel Reactive Antibody (PRA) was 0%. Patient developed both T and B cell Abs 1 month (m) post-Tx. B cell, but not T cell, Abs were reduced by DTT, indicating the presence of IgM Abs. The presence of auto-Abs was ruled out by auto-x-re. Platelet absorption depleted T cell PRA, with no effect on B cell PRA. The PRA dropped to 0% by 24m post-Tx. Patient developed lymphoma 3 years post-Tx. Cyclosporine therapy was reduced from 5mg to 1 mg/kg/day, while Imuran was discontinued. B cell PRA rose to 25%, 11% and 43% at 42, 44 and 49m post-Tx, respectively. These Abs were also reduced by DTT. X-m tests were performed with both pre-Tx donor T or B lymphocytes. T cell x-m was negative with all post-Tx sera samples. By contrast, B cell x-m was positive with all sera and were negative following DTT treatment. These findings indicate that T cell PRA, early post-Tx was due to transfusions, but B cell IgM Ab, which was developed in 2m post-Tx and reappeared at 42m, were donor-specific. Patient's lymphocytes from 42m post-Tx had specific reactivity toward pre-Tx donor cells and third party stimulator cells which shared HLA-DR1 with donor. At this time, patient's heart function was deteriorating and she was considered for re-Tx. However, due to the above findings, patient's immunosuppressive dose was increased and resulted in drop of PRA to 0% and reverse of rejection. Patient is doing well, off the re-Tx list and free of lymphoma. The above study indicates donor-specific class II antibodies and T lymphocytes in heart allograft which mediate immunologic reactivity and can be monitored by the above tests.
C-6.5 #138
SIGNIFICANCE OF THE FLOW CYTOMETRIC CROSSMATCH IN THE INITIAL EVALUATION OF POTENTIAL RENAL TRANSPLANT RECIPIENTS. RA Bray, MW Shuman, PT Chapman, JE Bray, GE Rodey. Dept. of Pathology, Emory University, Atlanta, GA. 30322. The flow cytometric crossmatch (FCXM) is continuing to grow in its utility as a final crossmatch method. However, one criticism of the FCXM is that it may be "too sensitive" and result in an increased percentage of "false positive" reactions thereby, inappropriately denying individuals the opportunity for transplantation. To address this issue, we retrospectively evaluated the results from 118 patients who were crossmatched with various family members as part of their initial work-up. All patients were crossmatched by both antiglobulin-enhanced cytotoxicity (AHG-CDC) and flow cytometry (FC). The AHG-CDC assay was performed using D'I-F treated and untreated serum while the FCXM was performed using an anti-lgG reagent and a three-color method that permits the simultaneous analysis of T and [] cells. Our findings revealed that in 104 (87%) of the patients both the AHG-CDC and the FCXM were negative. Fifteen patients exhibited a positive result with either the AHG-CDC or FCXM or both. Of the 15 positive results, one patient possessed an apparent IgM alloantibody that was reduced by DTT and was negative by the FCXM. Four patients exhibited IgG auto-reactive antibodies and four patients exhibited IgG allo-antibodies detectable by both AHG-CDC and FCXM. Six patients exhibited AHG-CDC negative / FCXM positive results. Five of the 6 patients were T and [] cell positive by FC and one patient was [] cell FC positive only. Of these six, only the AHG-CDC negative / FCXM [] cell positive patient appeared to be a truefalse positive as she reacted with her HLA identical sibling. Of the five AHG-CDC negative / FCXM positive individuals, all were multiparous females who exhibited AHG-CDC PRA values from 7-86% with 3/5 demonstrating specificity for the mismatched antigens. Two of the five were also multi-transfused. In summary, the FCXM does not appear to be "too sensitive" and, in fact, may be the most appropriate crossmatch method for the initial evaluation of potential renal transplant recipients, specifically multiparous females.
127
C-6.5 #137
DONOR-SPECIFIC HLA-DR ANTIBODIES MEDIATED REJECTION IN HEART TRANSPLANT. K Monahan, P Alivazatos, M Stone, L Dombrausky, A Nikaein. Baylor University Medical Center, Dallas, TX Long-term survival of heart allograft recipients is threatened mainly by chronic vascular rejection, which results in the development of graft atherosclerosis. Chronic rejection is dominated by the development of antibodies (Abs) to donor class I HLA antigens. In this report, we present a case of heart allograft recipient who developed anti-donor specific class II HLA Abs, donor HLA-DR-specific activated T cells and vascular endothelium injury with no pathologic sign of cellular or humoral rejection of the heart. Patient was a 53 year old female (HLA type A2,3;B18,39,DR8,13) who received a heart transplant (Tx) from a donor (HLA type A2,31 ;B8,62;DR1,3) across negative crossmatch (xm) with both donor T or B lymphocytes. Pre-Tx Panel Reactive Antibody (PRA) was 0%. Patient developed both T and B cell Abs 1 month (m) post-Tx. B cell, but not T cell, Abs were reduced by DTT, indicating the presence of IgM Abs. The presence of auto-Abs was ruled out by auto-x-re. Platelet absorption depleted T cell PRA, with no effect on B cell PRA. The PRA dropped to 0% by 24m post-Tx. Patient developed lymphoma 3 years post-Tx. Cyclosporine therapy was reduced from 5mg to 1 mg/kg/day, while Imuran was discontinued. B cell PRA rose to 25%, 11% and 43% at 42, 44 and 49m post-Tx, respectively. These Abs were also reduced by DTT. X-m tests were performed with both pre-Tx donor T or B lymphocytes. T cell x-m was negative with all post-Tx sera samples. By contrast, B cell x-m was positive with all sera and were negative following DTT treatment. These findings indicate that T cell PRA, early post-Tx was due to transfusions, but B cell IgM Ab, which was developed in 2m post-Tx and reappeared at 42m, were donor-specific. Patient's lymphocytes from 42m post-Tx had specific reactivity toward pre-Tx donor cells and third party stimulator cells which shared HLA-DR1 with donor. At this time, patient's heart function was deteriorating and she was considered for re-Tx. However, due to the above findings, patient's immunosuppressive dose was increased and resulted in drop of PRA to 0% and reverse of rejection. Patient is doing well, off the re-Tx list and free of lymphoma. The above study indicates donor-specific class II antibodies and T lymphocytes in heart allograft which mediate immunologic reactivity and can be monitored by the above tests.
C-6.5 #138
SIGNIFICANCE OF THE FLOW CYTOMETRIC CROSSMATCH IN THE INITIAL EVALUATION OF POTENTIAL RENAL TRANSPLANT RECIPIENTS. RA Bray, MW Shuman, PT Chapman, JE Bray, GE Rodey. Dept. of Pathology, Emory University, Atlanta, GA. 30322. The flow cytometric crossmatch (FCXM) is continuing to grow in its utility as a final crossmatch method. However, one criticism of the FCXM is that it may be "too sensitive" and result in an increased percentage of "false positive" reactions thereby, inappropriately denying individuals the opportunity for transplantation. To address this issue, we retrospectively evaluated the results from 118 patients who were crossmatched with various family members as part of their initial work-up. All patients were crossmatched by both antiglobulin-enhanced cytotoxicity (AHG-CDC) and flow cytometry (FC). The AHG-CDC assay was performed using D'I-F treated and untreated serum while the FCXM was performed using an anti-lgG reagent and a three-color method that permits the simultaneous analysis of T and [] cells. Our findings revealed that in 104 (87%) of the patients both the AHG-CDC and the FCXM were negative. Fifteen patients exhibited a positive result with either the AHG-CDC or FCXM or both. Of the 15 positive results, one patient possessed an apparent IgM alloantibody that was reduced by DTT and was negative by the FCXM. Four patients exhibited IgG auto-reactive antibodies and four patients exhibited IgG allo-antibodies detectable by both AHG-CDC and FCXM. Six patients exhibited AHG-CDC negative / FCXM positive results. Five of the 6 patients were T and [] cell positive by FC and one patient was [] cell FC positive only. Of these six, only the AHG-CDC negative / FCXM [] cell positive patient appeared to be a truefalse positive as she reacted with her HLA identical sibling. Of the five AHG-CDC negative / FCXM positive individuals, all were multiparous females who exhibited AHG-CDC PRA values from 7-86% with 3/5 demonstrating specificity for the mismatched antigens. Two of the five were also multi-transfused. In summary, the FCXM does not appear to be "too sensitive" and, in fact, may be the most appropriate crossmatch method for the initial evaluation of potential renal transplant recipients, specifically multiparous females.