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561: Relationship of Race and Socioeconomic Position with Rejection Incidence in Heart Transplant Recipients
The Journal of Heart and Lung Transplantation Volume 28, Number 2S
Abstracts
ventricular assist devices as rescue, better surgical technique, and/or more effective immunosuppression.
30-day Cause of Death Graft Failure n (%) Infection n (%) Cardiovascular n (%) Pulmonary n (%) Cerebrovascular n (%) Hemorrhage n (%) Malignancy n (%) Intra-op Non-hemorrhage n (%) Pancreatitis n (%) Renal Failure n (%) Liver Failure n (%) Multiple Organ Failure n (%)
1988-2007 (n⫽43,112) 1122 (2.6) 383 (0.9) 391 (0.9) 156 (0.4) 179 (0.4) 180 (0.4) 5 (0.01) 16 (0.04) 8 (0.02) 17 (0.04) 14 (0.03) 300 (0.7)
Overall p-trend 0.002 0.41 0.77 0.56 0.77 0.94 0.97 0.99 0.97 1.00 0.99 0.75
561 Relationship of Race and Socioeconomic Position with Rejection Incidence in Heart Transplant Recipients T.P. Singh1, M. Semigran2, K. Gauvreau1, F. Costantino4, D. DeNofrio5, S. Evans1, M. Givertz3 1Children’s Hospital Boston, Boston, MA; 2Massachussets General Hospital, Boston, MA; 3 Brigham and Women’s Hospital, Boston, MA; 4New England Organ Bank, Watertown, MA; 5Tufts Medical Center, Boston, MA Purpose: Recent studies suggest that the association of race with outcomes in heart transplant (HT) recipients may be mediated by genetic factors. Block groups (average population 1000) are the smallest units of population in US census database with available SE data. We assessed if SE position, determined for the block group of patient residence, is associated with risk of rejection in HT recipients. Methods and Materials: We used the US census 2000 database to extract 6 SE variables of income, wealth, education and occupation and calculated a previously validated SE score for 520 patients (median age 51 years, range 7 days to 71 years) who underwent first HT at one of 4 Boston centers during 1996-2005. A Cox proportional hazards model was used to compare time to first rejection and a Poisson regression model to compare the incidence rate (IR) of any rejection in the lowest quartile SE group (low SE group, n⫽129) with that of remaining patients (controls, n⫽391). Results: Low SE patients were more likely to be nonwhite (32% versus 9% of controls, P⬍0.001). Rejection episodes occurred in 209 (40%) patients. In univariate analysis, shorter time to first rejection was associated with younger age, female gender and low SE position (Hazard ratio HR 1.4, 95% confidence interval CI 1.1-1.9, P⫽0.02) but not race. IR for any rejection was associated with younger age, female gender, pre-HT ventricular assist device (VAD), low SE position (IR ratio 1.5, CI 1.2-1.9, P⫽0.001) and nonwhite race (IR ratio 1.8, CI 1.4-2.3, P⬍0.001). In multivariable regression analyses, predictors for first rejection were pre-HT VAD and low SE position (HR 1.4, CI 1.0-1.9, P⫽0.06) and for IR of any rejection included female gender, earlier era, pre-HT VAD, low SE position (IR ratio 1.3, CI 1.0-1.7, P⫽0.03) and nonwhite race (IR ratio 1.5, CI 1.1-1.9, P⫽0.007). Conclusions: Rejection episodes are more common in nonwhite HT recipients and those in low SE position. The association of race with outcomes in HT recipients may be mediated in part by SE factors. 562 The Maintenance of Peripheral Tolerance Following Porcine Lung Transplantation Is Alloantigen Specific G. Warnecke1, B. Kruse1, S. Thissen1, M. Avsar1, C. Matiaske1, J.H. Karstens2, A.R. Simon1, A. Haverich1, M. Struber1 1Hannover Medical School, Hannover, Germany; 2Hannover Medical School, Hannover, Germany
S261
Purpose: Donor splenocyte infusion has been shown to induce T cell regulation and transplant tolerance in a model of porcine allogeneic lung transplantation. Here, we wished to study alloantigen requirements in the induction and maintenance of such tolerance. Methods and Materials: Left-sided lung transplantation from MHC mismatched donors was performed in 13 adult minipigs. Intravenous pharmacologic immunosuppression was withdrawn after 28 postoperative days. All animals received a splenocyte infusion on the day of lung transplantation, either from the lung donor, or from a MHC mismatched third party donor. All received non myeloablative irradiation one day before transplant. Allograft survival was monitored by chest radiographs and transbronchial biopsies. The immune phenotype was monitored from peripheral blood and bronchoalveolar lavage fluid (BALF) by FACS analysis. Some of the long term survivors received orthotopic third party kidney transplants more than 600 days after lung transplantation. Results: Transplant survival was prolonged beyond 200 days in the group receiving donor splenocytes. Upon infusion of third party splenocytes, 2 out of 6 animals rejected before day 200, but the remainder developed stable tolerance. High levels of CD4⫹CD25high⫹ regulatory T cells were present both in the peripheral blood and in BALF of eventual long term survivors. Long term survivors rejected secondary third party kidney transplants acutely within 5 days without injury to their pulmonary grafts. Conclusions: This data shows that the infusion of non-specific alloantigen at the time of transplant is nearly as efficient as donorspecific alloantigen. However, the ensuing state of tolerance itself is strictly alloantigen-specific. 563 Development of Transplant Arteriosclerosis in Porcinized Mice Is Regulated by Allogeneic Porcine CD4ⴙCD25ⴙ T Cells N. Madrahimov, A.-K. Knofel, G. Warnecke, S. Thissen, B. Kruse, M. Avsar, C. Matiaske, S. Fischer, A. Haverich, M. Struber Hannover Medical School, Hannover, Germany Purpose: We have shown previously that long term graft acceptance correlated with the frequency of CD4⫹CD25⫹ regulatory T cells in a porcine allogeneic lung transplantation model. However, it is unknown, if this type of T cell regulation is the cause for or merely an epiphenomenon of long term allograft survival. Xenogeneic cell and tissue transplantation into immunodeficient mice represent valuable tools to study this regulation in vivo. Therefore, we implanted porcine arteries and adoptively transferred porcine PBMC into NODrag-/-gammac-/- mice. Methods and Materials: Porcine intercostal arteries were implanted into the murine abdominal aorta. Group A additionally received 10⫻106 autologous porcine PBMC (graft and cells were obtained from the same pig), group B cells and vessels were collected from two MHC mismatched pigs and group C recipients received allogeneic PBMC depleted of CD4⫹CD25⫹ cells. Porcine CD45⫹ cell engraftment was monitored by FACS postoperatively. Transplant arteriosclerosis was histologically assessed on postoperative day (POD) 28. Quantification was done by measuring intima to media ratio. Results: Porcine cell proliferation in groups A and B had an average increase from 1% on POD14 to 3% on POD28 (p⬍0.05). Animals which received PBMC depleted of CD4⫹CD25⫹ cells, showed comparatively higher proliferation rates at POD14 with a decrease (p⬍0,05) by POD28 (3.5 % vs ⬍1 %, respectively). Moreover, graft arteriosclerosis was different among groups (p⬍0.05) and severely pronounced in group C. Mean intima to media ratio was higher (p⬍0,05) in group C compared to groups A and B respectively (80.3⫹/-11.6% vs 23.8⫹/-5.2 % and 47.7⫹/-13.6 %). Conclusions: Thus, reconstitution of NODrag-/-gammac-/- mice with CD4⫹CD25⫹ T cell-depleted PBMC led to an early and exhaustive
Abstracts
ventricular assist devices as rescue, better surgical technique, and/or more effective immunosuppression.
30-day Cause of Death Graft Failure n (%) Infection n (%) Cardiovascular n (%) Pulmonary n (%) Cerebrovascular n (%) Hemorrhage n (%) Malignancy n (%) Intra-op Non-hemorrhage n (%) Pancreatitis n (%) Renal Failure n (%) Liver Failure n (%) Multiple Organ Failure n (%)
1988-2007 (n⫽43,112) 1122 (2.6) 383 (0.9) 391 (0.9) 156 (0.4) 179 (0.4) 180 (0.4) 5 (0.01) 16 (0.04) 8 (0.02) 17 (0.04) 14 (0.03) 300 (0.7)
Overall p-trend 0.002 0.41 0.77 0.56 0.77 0.94 0.97 0.99 0.97 1.00 0.99 0.75
561 Relationship of Race and Socioeconomic Position with Rejection Incidence in Heart Transplant Recipients T.P. Singh1, M. Semigran2, K. Gauvreau1, F. Costantino4, D. DeNofrio5, S. Evans1, M. Givertz3 1Children’s Hospital Boston, Boston, MA; 2Massachussets General Hospital, Boston, MA; 3 Brigham and Women’s Hospital, Boston, MA; 4New England Organ Bank, Watertown, MA; 5Tufts Medical Center, Boston, MA Purpose: Recent studies suggest that the association of race with outcomes in heart transplant (HT) recipients may be mediated by genetic factors. Block groups (average population 1000) are the smallest units of population in US census database with available SE data. We assessed if SE position, determined for the block group of patient residence, is associated with risk of rejection in HT recipients. Methods and Materials: We used the US census 2000 database to extract 6 SE variables of income, wealth, education and occupation and calculated a previously validated SE score for 520 patients (median age 51 years, range 7 days to 71 years) who underwent first HT at one of 4 Boston centers during 1996-2005. A Cox proportional hazards model was used to compare time to first rejection and a Poisson regression model to compare the incidence rate (IR) of any rejection in the lowest quartile SE group (low SE group, n⫽129) with that of remaining patients (controls, n⫽391). Results: Low SE patients were more likely to be nonwhite (32% versus 9% of controls, P⬍0.001). Rejection episodes occurred in 209 (40%) patients. In univariate analysis, shorter time to first rejection was associated with younger age, female gender and low SE position (Hazard ratio HR 1.4, 95% confidence interval CI 1.1-1.9, P⫽0.02) but not race. IR for any rejection was associated with younger age, female gender, pre-HT ventricular assist device (VAD), low SE position (IR ratio 1.5, CI 1.2-1.9, P⫽0.001) and nonwhite race (IR ratio 1.8, CI 1.4-2.3, P⬍0.001). In multivariable regression analyses, predictors for first rejection were pre-HT VAD and low SE position (HR 1.4, CI 1.0-1.9, P⫽0.06) and for IR of any rejection included female gender, earlier era, pre-HT VAD, low SE position (IR ratio 1.3, CI 1.0-1.7, P⫽0.03) and nonwhite race (IR ratio 1.5, CI 1.1-1.9, P⫽0.007). Conclusions: Rejection episodes are more common in nonwhite HT recipients and those in low SE position. The association of race with outcomes in HT recipients may be mediated in part by SE factors. 562 The Maintenance of Peripheral Tolerance Following Porcine Lung Transplantation Is Alloantigen Specific G. Warnecke1, B. Kruse1, S. Thissen1, M. Avsar1, C. Matiaske1, J.H. Karstens2, A.R. Simon1, A. Haverich1, M. Struber1 1Hannover Medical School, Hannover, Germany; 2Hannover Medical School, Hannover, Germany
S261
Purpose: Donor splenocyte infusion has been shown to induce T cell regulation and transplant tolerance in a model of porcine allogeneic lung transplantation. Here, we wished to study alloantigen requirements in the induction and maintenance of such tolerance. Methods and Materials: Left-sided lung transplantation from MHC mismatched donors was performed in 13 adult minipigs. Intravenous pharmacologic immunosuppression was withdrawn after 28 postoperative days. All animals received a splenocyte infusion on the day of lung transplantation, either from the lung donor, or from a MHC mismatched third party donor. All received non myeloablative irradiation one day before transplant. Allograft survival was monitored by chest radiographs and transbronchial biopsies. The immune phenotype was monitored from peripheral blood and bronchoalveolar lavage fluid (BALF) by FACS analysis. Some of the long term survivors received orthotopic third party kidney transplants more than 600 days after lung transplantation. Results: Transplant survival was prolonged beyond 200 days in the group receiving donor splenocytes. Upon infusion of third party splenocytes, 2 out of 6 animals rejected before day 200, but the remainder developed stable tolerance. High levels of CD4⫹CD25high⫹ regulatory T cells were present both in the peripheral blood and in BALF of eventual long term survivors. Long term survivors rejected secondary third party kidney transplants acutely within 5 days without injury to their pulmonary grafts. Conclusions: This data shows that the infusion of non-specific alloantigen at the time of transplant is nearly as efficient as donorspecific alloantigen. However, the ensuing state of tolerance itself is strictly alloantigen-specific. 563 Development of Transplant Arteriosclerosis in Porcinized Mice Is Regulated by Allogeneic Porcine CD4ⴙCD25ⴙ T Cells N. Madrahimov, A.-K. Knofel, G. Warnecke, S. Thissen, B. Kruse, M. Avsar, C. Matiaske, S. Fischer, A. Haverich, M. Struber Hannover Medical School, Hannover, Germany Purpose: We have shown previously that long term graft acceptance correlated with the frequency of CD4⫹CD25⫹ regulatory T cells in a porcine allogeneic lung transplantation model. However, it is unknown, if this type of T cell regulation is the cause for or merely an epiphenomenon of long term allograft survival. Xenogeneic cell and tissue transplantation into immunodeficient mice represent valuable tools to study this regulation in vivo. Therefore, we implanted porcine arteries and adoptively transferred porcine PBMC into NODrag-/-gammac-/- mice. Methods and Materials: Porcine intercostal arteries were implanted into the murine abdominal aorta. Group A additionally received 10⫻106 autologous porcine PBMC (graft and cells were obtained from the same pig), group B cells and vessels were collected from two MHC mismatched pigs and group C recipients received allogeneic PBMC depleted of CD4⫹CD25⫹ cells. Porcine CD45⫹ cell engraftment was monitored by FACS postoperatively. Transplant arteriosclerosis was histologically assessed on postoperative day (POD) 28. Quantification was done by measuring intima to media ratio. Results: Porcine cell proliferation in groups A and B had an average increase from 1% on POD14 to 3% on POD28 (p⬍0.05). Animals which received PBMC depleted of CD4⫹CD25⫹ cells, showed comparatively higher proliferation rates at POD14 with a decrease (p⬍0,05) by POD28 (3.5 % vs ⬍1 %, respectively). Moreover, graft arteriosclerosis was different among groups (p⬍0.05) and severely pronounced in group C. Mean intima to media ratio was higher (p⬍0,05) in group C compared to groups A and B respectively (80.3⫹/-11.6% vs 23.8⫹/-5.2 % and 47.7⫹/-13.6 %). Conclusions: Thus, reconstitution of NODrag-/-gammac-/- mice with CD4⫹CD25⫹ T cell-depleted PBMC led to an early and exhaustive