2011 - IPITA - Prague
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Poster
1.176 - Role of immunosuppressive therapy on humoral autoimmune response after islet allotransplantation: long term survey
Presenter: P. , Maffi1, ,
Authors: P. Maffi1, F. Mescia1, M. Scavini1, R. Nano2, P. Magistretti1, R. Melzi2, E. Bosi2, L. Piemonti2, A. Secchi1
P-176
Role of immunosuppressive therapy on humoral autoimmune response after islet allotransplantation: long term survey
P. Maffi1, F. Mescia1, M. Scavini1, R. Nano2, P. Magistretti1, R. Melzi2, E. Bosi2, L. Piemonti2, A. Secchi1
1 Scientific Institute San Raffaele, Diabetes Research Institute - Transplant Medicine, Milan, Italy; 2 Scientific Institute San Raffaele, Diabetes Research Institute , Milan, Italy
Backgroung: It is known that the presence of autoantibodies before islet transplantation is a negative predicting factor of graft function.
Objective: The aim of our study was to correlate the trend of autoantibodies values after islet allotransplantation under different immunosuppressive protocols.
Methods: 36 patients receiving islet transplant alone and 14 patients receiving islet transplant with kidney (3 SIK, 11 IAK) were included in this analysis. The immunosuppressive protocols were: A)Edmonton: n=14; B)pre-transplant treatment with rapamycin+Edmonton: n=9; C)ATG+ rapamycin+MMF: n=3; D)ATG+MMF+FK506: n=2; E)ATG+anakinra+rapamycin pretreatment/maintenance+MMF: n=8; F)daclizumab/basiliximab+calcineurin inhibitor+ MMF/azathioprine: n=10; G)daclizumab+rapamycin+MMF: n=1; H)ATG+prednisone (tapering over 6 months)+MMF+FK506 n=3.
We measured the serum T1D-associated autoantibodies GAD65 and IA-2 before islet transplantation and at: day 1,3,5,7,14,28,2 months,3 months,6 months and every 6 months from then onward. We collectively regarded seroconversions for either autoantigen specificity and increases in autoantibody titers >2x baseline levels as autoantibody rise events.
Results: The following table summarizes findings, distinguishing autoAb rises between early and late events on the basis of timing (before or following 30 days from first infusion).
rapamycin | ATG | Early rise | Late rise | Overall rise | ||
ITA | A n=14 | yes | no | 3 | 3 | 6 |
B n=9 | yes | no | 1 | 2 | 3 | |
C n=3 | yes | no | 0 | 0 | 0 | |
D n=2 | no | yes | 1 | 0 | 1 | |
E n=8 | yes | yes | 0 | 1 | 1 | |
IAK | F n=10 | no | no | 6 | 1 | 7 |
G n=1 | yes | no | 0 | 0 | 0 | |
SIK | H n=3 | no | yes | 1 | 1 | 2 |
Conclusions: Logistic regression showed that patients treated with rapamycin are less likely to display a rise in T1D-associated autoantibodies during the first 30 days following first islet infusion (odds ratio 0.11, 95% CI 0.03-0.49; p=0.004). This result is independent of treatment with ATG, but not on transplant type (SIK vs. non-SIK). Rapamycin treatment did not appear to associate significantly with late rise events.
/P-176
Role of immunosuppressive therapy on humoral autoimmune response after islet allotransplantation: long term survey
P. Maffi1, F. Mescia1, M. Scavini1, R. Nano2, P. Magistretti1, R. Melzi2, E. Bosi2, L. Piemonti2, A. Secchi1
1 Scientific Institute San Raffaele, Diabetes Research Institute - Transplant Medicine, Milan, Italy; 2 Scientific Institute San Raffaele, Diabetes Research Institute , Milan, Italy
Backgroung: It is known that the presence of autoantibodies before islet transplantation is a negative predicting factor of graft function.
Objective: The aim of our study was to correlate the trend of autoantibodies values after islet allotransplantation under different immunosuppressive protocols.
Methods: 36 patients receiving islet transplant alone and 14 patients receiving islet transplant with kidney (3 SIK, 11 IAK) were included in this analysis. The immunosuppressive protocols were: A)Edmonton: n=14; B)pre-transplant treatment with rapamycin+Edmonton: n=9; C)ATG+ rapamycin+MMF: n=3; D)ATG+MMF+FK506: n=2; E)ATG+anakinra+rapamycin pretreatment/maintenance+MMF: n=8; F)daclizumab/basiliximab+calcineurin inhibitor+ MMF/azathioprine: n=10; G)daclizumab+rapamycin+MMF: n=1; H)ATG+prednisone (tapering over 6 months)+MMF+FK506 n=3.
We measured the serum T1D-associated autoantibodies GAD65 and IA-2 before islet transplantation and at: day 1,3,5,7,14,28,2 months,3 months,6 months and every 6 months from then onward. We collectively regarded seroconversions for either autoantigen specificity and increases in autoantibody titers >2x baseline levels as autoantibody rise events.
Results: The following table summarizes findings, distinguishing autoAb rises between early and late events on the basis of timing (before or following 30 days from first infusion).
rapamycin | ATG | Early rise | Late rise | Overall rise | ||
ITA | A n=14 | yes | no | 3 | 3 | 6 |
B n=9 | yes | no | 1 | 2 | 3 | |
C n=3 | yes | no | 0 | 0 | 0 | |
D n=2 | no | yes | 1 | 0 | 1 | |
E n=8 | yes | yes | 0 | 1 | 1 | |
IAK | F n=10 | no | no | 6 | 1 | 7 |
G n=1 | yes | no | 0 | 0 | 0 | |
SIK | H n=3 | no | yes | 1 | 1 | 2 |
Conclusions: Logistic regression showed that patients treated with rapamycin are less likely to display a rise in T1D-associated autoantibodies during the first 30 days following first islet infusion (odds ratio 0.11, 95% CI 0.03-0.49; p=0.004). This result is independent of treatment with ATG, but not on transplant type (SIK vs. non-SIK). Rapamycin treatment did not appear to associate significantly with late rise events.
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