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479 First -Year Rejection and Cylex Scores Suggest the Importance of Acute Events in the Development of Cardiac Allograft Vasculopathy
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The Journal of Heart and Lung Transplantation, Vol 31, No 4S, April 2012
vs 8.5⫾3.9 mg, P⫽NS), TAC level (7.3⫾2.2 vs 8.6⫾3.1, P⫽NS) and prednisone dose (14.4⫾5.0 mg vs 13.6⫾3.1 mg, P⫽NS) did not differ by gender. Nearly the entire female cohort were AA (88% vs 50% of the men; P⫽0.07) and men had higher serum creatinine (0.8⫾0.2 mg/dL vs 1.3⫾0.4 mg/dL, P⫽0.002).
Methods and Materials: We measured Immuknow, concentration of 12 cytokines and sCD30 in blood collected at the time of routine endomyocardial biopsy and when clinically indicated. CAV was defined as new coronary artery disease (CAD) detected by angiography or a significant worsening (increase in coronary stenosis 50% or more) of previously diagnosed CAD. Results: We collected 162 samples from 56 cardiac transplant recipients. CAV was identified in 4 patients. Significant correlation was observed between CAV and TNF-␣ and IL8 (P⫽0.001). ROC curve was constructed to test the performance of TNF-␣ and IL8 in predicting CAV and showed a maximum efficiency for TNF-␣ at ⱖ 38ng/ml (sensitivity 66.67%, specificity 97.74%), and a maximum efficiency for IL8 at ⱖ2.2ng/ml (sensitivity 66.67%, specificity 82.71%). No significant correlation between CAV and other immune function parameters was identified. Conclusions: Our data suggest strong correlation between CAV and TNF-␣ which initiates the proinflammatory response. A significant correlation is also seen with IL-8 which is a potent proinflammatory and chemotactic cytokine. These findings may indicate a major role for these cytokines in the pathogenesis of CAV and should be validated in a larger patient cohort. 479 First -Year Rejection and Cylex Scores Suggest the Importance of Acute Events in the Development of Cardiac Allograft Vasculopathy M. Rafiei, J. Patel, M. Kittleson, N. Patel, L. Stern, B. Azarbal, L. Czer, A. Trento, J. Kobashigawa. Cedars-Sinai Heart Institute, Los Angeles, CA.
Conclusions: In this single center study, a predominantly AA cohort of women had lower GEP scores than men early after HT despite similar immune modulating rx. Gender specific sensitivity of the GEP to clinical events and immune rx early post HT may exist. Further studies examining the interaction of race, gender and components of the GEP are needed. 478 TNF -␣ and IL-8 Predict Cardiac Vasculopathy after Cardiac Transplantation N. Heikal,1,2 H. Hill,1,2,3,4 T. Martins,1 I. Pavlov,1 A. Wilson,1 J. Stehlik,4 A. Kfoury,4 J. Delgado,1,2 F. Bader.4 1ARUP Institute for Clinical and Experimental Pathology, SLC, UT; 2Department of Pathology, SLC; 3Pediatrics and Medicine, SLC; 4Division of Cardiology, University of Utah School of Medicine, SLC. Purpose: Cardiac allograft vasculopathy (CAV) is a major cause of mortality after heart transplantation. Yearly coronary angiograms are performed post transplantation to screen for CAV. Accurate non-invasive screening tests for CAV might decrease the need for coronary angiograms. Cellular and humoral immune responses have been implicated in the development of CAV; we hypothesized that immune function and cytokine expression could potentially provide information regarding the development of CAV.
Purpose: Antibody-mediated rejection (AMR) and cellular rejection (CR) have been implicated in the development of CAV. Immune monitoring (Cylex®) represents T-cell immune responses and has been demonstrated to represent immune responsiveness in patients following heart transplant. Patients who are under-immunosuppressed per Cylex score in the first-year after heart transplant may be at risk to develop more CAV regardless of CR. Therefore, to assess the impact of chronic immune responsiveness and acute cellular and humoral events on the development of CAV, we reviewed the first year average Cylex score and incidence of first-year AMR and CR in our heart transplant patients. Methods and Materials: Between 2005 and 2010, we evaluated, 206 cardiac transplant patients who had a minimum of three Cylex scores in the first-year following transplant. The average scores were then correlated to those patients who did and did not develop CAV (defined as any angiographic stenosis ⱖ 30%) within the first three years after transplant. The incidence of first-year AMR and CR was recorded for these patients. Results: Out of the 206 patients, there were 5 patients who developed CAV within the first three years following cardiac transplantation. The average first-year Cylex score was similar for those patients who developed CAV compared to those patients who did not develop CAV (292 ⫾ 132 ATP ng/mL vs. 297 ⫾ 115 ATP ng/mL, p ⫽ 0.92). The 5 patients with CAV had significantly more AMR (40% vs. 8%, p ⫽ 0.01) and CR (40% vs. 11%, p ⫽ 0.05) compared to patients with no CAV. Conclusions: Mean Cylex score in the first-year after HTx, as a measure of T-cell immune function, is not a useful biomarker to predict the subsequent development of CAV. However, first-year AMR and CR was associated with the development of CAV which suggests that the clinical development of acute rejection may be more important than the chronic state of T-cell immune responsiveness in the development of CAV. 480 Donor Specific Anti-HLA Antibody Detection in Heart Transplantation: Comparison of a Donor-Specific Bead-Based Crossmatch Technique with Flow-Crossmatch and Single-Antigen Bead Methodology A. Chaidaroglou,1 A. Skoura,1 A. Gouziouta,2 D. Degiannis.1 1Molecular Immunopathology and Histocompatibility Laboratory, Onassis Cardiac Surgery Center, Athens, Greece; 22nd Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece. Purpose: In the present study we analyzed the efficiency of three different laboratory methodologies for the detection of donor-specific anti-HLA antibodies (DSA), their degree of correlation and their clinical relevance.
The Journal of Heart and Lung Transplantation, Vol 31, No 4S, April 2012
vs 8.5⫾3.9 mg, P⫽NS), TAC level (7.3⫾2.2 vs 8.6⫾3.1, P⫽NS) and prednisone dose (14.4⫾5.0 mg vs 13.6⫾3.1 mg, P⫽NS) did not differ by gender. Nearly the entire female cohort were AA (88% vs 50% of the men; P⫽0.07) and men had higher serum creatinine (0.8⫾0.2 mg/dL vs 1.3⫾0.4 mg/dL, P⫽0.002).
Methods and Materials: We measured Immuknow, concentration of 12 cytokines and sCD30 in blood collected at the time of routine endomyocardial biopsy and when clinically indicated. CAV was defined as new coronary artery disease (CAD) detected by angiography or a significant worsening (increase in coronary stenosis 50% or more) of previously diagnosed CAD. Results: We collected 162 samples from 56 cardiac transplant recipients. CAV was identified in 4 patients. Significant correlation was observed between CAV and TNF-␣ and IL8 (P⫽0.001). ROC curve was constructed to test the performance of TNF-␣ and IL8 in predicting CAV and showed a maximum efficiency for TNF-␣ at ⱖ 38ng/ml (sensitivity 66.67%, specificity 97.74%), and a maximum efficiency for IL8 at ⱖ2.2ng/ml (sensitivity 66.67%, specificity 82.71%). No significant correlation between CAV and other immune function parameters was identified. Conclusions: Our data suggest strong correlation between CAV and TNF-␣ which initiates the proinflammatory response. A significant correlation is also seen with IL-8 which is a potent proinflammatory and chemotactic cytokine. These findings may indicate a major role for these cytokines in the pathogenesis of CAV and should be validated in a larger patient cohort. 479 First -Year Rejection and Cylex Scores Suggest the Importance of Acute Events in the Development of Cardiac Allograft Vasculopathy M. Rafiei, J. Patel, M. Kittleson, N. Patel, L. Stern, B. Azarbal, L. Czer, A. Trento, J. Kobashigawa. Cedars-Sinai Heart Institute, Los Angeles, CA.
Conclusions: In this single center study, a predominantly AA cohort of women had lower GEP scores than men early after HT despite similar immune modulating rx. Gender specific sensitivity of the GEP to clinical events and immune rx early post HT may exist. Further studies examining the interaction of race, gender and components of the GEP are needed. 478 TNF -␣ and IL-8 Predict Cardiac Vasculopathy after Cardiac Transplantation N. Heikal,1,2 H. Hill,1,2,3,4 T. Martins,1 I. Pavlov,1 A. Wilson,1 J. Stehlik,4 A. Kfoury,4 J. Delgado,1,2 F. Bader.4 1ARUP Institute for Clinical and Experimental Pathology, SLC, UT; 2Department of Pathology, SLC; 3Pediatrics and Medicine, SLC; 4Division of Cardiology, University of Utah School of Medicine, SLC. Purpose: Cardiac allograft vasculopathy (CAV) is a major cause of mortality after heart transplantation. Yearly coronary angiograms are performed post transplantation to screen for CAV. Accurate non-invasive screening tests for CAV might decrease the need for coronary angiograms. Cellular and humoral immune responses have been implicated in the development of CAV; we hypothesized that immune function and cytokine expression could potentially provide information regarding the development of CAV.
Purpose: Antibody-mediated rejection (AMR) and cellular rejection (CR) have been implicated in the development of CAV. Immune monitoring (Cylex®) represents T-cell immune responses and has been demonstrated to represent immune responsiveness in patients following heart transplant. Patients who are under-immunosuppressed per Cylex score in the first-year after heart transplant may be at risk to develop more CAV regardless of CR. Therefore, to assess the impact of chronic immune responsiveness and acute cellular and humoral events on the development of CAV, we reviewed the first year average Cylex score and incidence of first-year AMR and CR in our heart transplant patients. Methods and Materials: Between 2005 and 2010, we evaluated, 206 cardiac transplant patients who had a minimum of three Cylex scores in the first-year following transplant. The average scores were then correlated to those patients who did and did not develop CAV (defined as any angiographic stenosis ⱖ 30%) within the first three years after transplant. The incidence of first-year AMR and CR was recorded for these patients. Results: Out of the 206 patients, there were 5 patients who developed CAV within the first three years following cardiac transplantation. The average first-year Cylex score was similar for those patients who developed CAV compared to those patients who did not develop CAV (292 ⫾ 132 ATP ng/mL vs. 297 ⫾ 115 ATP ng/mL, p ⫽ 0.92). The 5 patients with CAV had significantly more AMR (40% vs. 8%, p ⫽ 0.01) and CR (40% vs. 11%, p ⫽ 0.05) compared to patients with no CAV. Conclusions: Mean Cylex score in the first-year after HTx, as a measure of T-cell immune function, is not a useful biomarker to predict the subsequent development of CAV. However, first-year AMR and CR was associated with the development of CAV which suggests that the clinical development of acute rejection may be more important than the chronic state of T-cell immune responsiveness in the development of CAV. 480 Donor Specific Anti-HLA Antibody Detection in Heart Transplantation: Comparison of a Donor-Specific Bead-Based Crossmatch Technique with Flow-Crossmatch and Single-Antigen Bead Methodology A. Chaidaroglou,1 A. Skoura,1 A. Gouziouta,2 D. Degiannis.1 1Molecular Immunopathology and Histocompatibility Laboratory, Onassis Cardiac Surgery Center, Athens, Greece; 22nd Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece. Purpose: In the present study we analyzed the efficiency of three different laboratory methodologies for the detection of donor-specific anti-HLA antibodies (DSA), their degree of correlation and their clinical relevance.