Differences in Baseline Lymphocyte Counts and Autoreactivity Are Associated With Differences in Outcome of Islet Cell Transplantation in Type 1 Diabetic Patients

被引:84
作者
Hilbrands, Robert [1 ,2 ,3 ]
Huurman, Volkert A. L. [3 ,4 ]
Gillard, Pieter [1 ,2 ,3 ,5 ]
Velthuis, Jurjen H. L. [3 ,4 ]
De Waele, Marc [1 ,2 ]
Mathieu, Chantal [3 ,5 ]
Kaufman, Leonard [6 ]
Pipeleers-Marichal, Miriam [1 ,2 ]
Ling, Zhidong [1 ,2 ,3 ]
Movahedi, Babak [1 ,2 ,3 ]
Jacobs-Tulleneers-Thevissen, Daniel [1 ,2 ,3 ]
Monbaliu, Diethard [7 ]
Ysebaert, Dirk [8 ]
Gorus, Frans K. [1 ,2 ,3 ]
Roep, Bart O. [3 ,4 ]
Pipeleers, Daniel G. [1 ,2 ,3 ]
Keymeulen, Bart [1 ,2 ,3 ]
机构
[1] Vrije Univ Brussel, Free Univ Brussels, Diabet Res Ctr, Brussels, Belgium
[2] Vrije Univ Brussel, Free Univ Brussels, Universitair Ziekenhuis Brussels, Brussels, Belgium
[3] Juvenile Diabet Res Fdn, Ctr Cell Therapy Diabet, Brussels, Belgium
[4] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands
[5] Catholic Univ Louvain, Dept Endocrinol, Universitair Ziekenhuis Brussels, B-3000 Louvain, Belgium
[6] Brussels Free Univ VUB, Dept Biostat, Brussels, Belgium
[7] Catholic Univ Louvain, Universitair Ziekenhuis Brussels, Dept Surg, B-3000 Louvain, Belgium
[8] Univ Antwerp, Universitair Ziekenhuis Brussels, Dept Surg, B-2020 Antwerp, Belgium
关键词
B-CELLS; INSULIN-INDEPENDENCE; ANTIGEN PRESENTATION; TOTAL PANCREATECTOMY; ALLOGRAFT SURVIVAL; CULTURED ISLETS; LIVER SEGMENT; MELLITUS; GRAFT; IMMUNOSUPPRESSION;
D O I
10.2337/db09-0160
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE-The metabolic outcome of islet cell transplants in type 1 diabetic patients is variable. This retrospective analysis examines whether differences in recipient characteristics at the time of transplantation are correlated with inadequate graft function. RESEARCH DESIGN AND METHODS-Thirty nonuremic C-peptide-negative type 1 diabetic patients had received an intraportal islet cell graft of comparable size under an ATG-tacrolimus-mycophenolate mofetil regimen. Baseline patient characteristics were compared with outcome parameters during the first 6 posttransplant months (i.e., plasma C-peptide, glycemic variability, and gain of insulin independence). Correlations in univariate analysis were further examined in a multivariate model. RESULTS-Patients that did not become insulin independent exhibited significantly higher counts of B-cells as well as a T-cell autoreactivity against insulinoma-associated protein 2 (IA2) and/or GAD. In one of them, a liver biopsy during posttransplant year 2 showed B-cell accumulations near insulin-positive P-cell aggregates. Higher baseline total lymphocytes and T-cell autoreactivity were also correlated with lower plasma C-peptide levels and higher glycemic variability. CONCLUSIONS-Higher total and B-cell counts and presence of T-cell autoreactivity at baseline are independently associated with lower graft function in type 1 diabetic patients receiving intraportal islet cells under ATG-tacrolimus-mycophenolate mofetil therapy. Prospective studies are needed to assess whether control of these characteristics can help increase the function of islet cell grafts during the first year posttransplantation. Diabetes 58:2267-2276, 2009
引用
收藏
页码:2267 / 2276
页数:10
相关论文
共 52 条
[1]   Factors associated with insulin and narcotic independence after islet autotransplantation in patients with severe chronic pancreatitis [J].
Ahmad, SA ;
Lowy, AM ;
Wray, CJ ;
D'Alessio, D ;
Choe, KA ;
James, LE ;
Gelrud, A ;
Matthews, JB ;
Rilo, HLR .
JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS, 2005, 201 (05) :680-687
[2]  
Ault A, 2003, LANCET, V361, P2054
[3]   INSULIN-DEPENDENT DIABETES-MELLITUS AS AN AUTOIMMUNE-DISEASE [J].
BACH, JF .
ENDOCRINE REVIEWS, 1994, 15 (04) :516-542
[4]   Autoantibody response to islet transplantation in type 1 diabetes [J].
Bosi, E ;
Braghi, S ;
Maffi, P ;
Scirpoli, M ;
Bertuzzi, F ;
Pozza, G ;
Secchi, A ;
Bonifacio, E .
DIABETES, 2001, 50 (11) :2464-2471
[5]   B-cells promote intra-islet CD8+ cytotoxic T-cell survival to enhance type 1 diabetes [J].
Brodie, Gillian M. ;
Wallberg, Maja ;
Santamaria, Pere ;
Wong, F. Susan ;
Green, E. Allison .
DIABETES, 2008, 57 (04) :909-917
[6]   B cells move to centre stage: novel opportunities for autoimmune disease treatment [J].
Browning, Jeffrey L. .
NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (07) :564-576
[7]   High risk of sensitization after failed islet transplantation [J].
Campbell, P. M. ;
Senior, P. A. ;
Salam, A. ;
LaBranche, K. ;
Bigam, D. L. ;
Kneteman, N. M. ;
Imes, S. ;
Halpin, A. ;
Ryan, E. A. ;
Shapiro, A. M. J. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2007, 7 (10) :2311-2317
[8]   Allosensitization of islet allograft recipients [J].
Cardani, Roberta ;
Pileggi, Antonello ;
Ricordi, Camillo ;
Gomez, Carmen ;
Baidal, David A. ;
Ponte, Gaston G. ;
Mineo, Davide ;
Faradji, Raquel N. ;
Froud, Tatiana ;
Ciancio, Gaetano ;
Esquenazi, Violet ;
Burke, George W., III ;
Selvaggi, Gennaro ;
Miller, Joshua ;
Kenyon, Norma S. ;
Alejandro, Rodolfo .
TRANSPLANTATION, 2007, 84 (11) :1413-1427
[9]   Antibody-mediated organ-allograft rejection [J].
Colvin, RB ;
Smith, RN .
NATURE REVIEWS IMMUNOLOGY, 2005, 5 (10) :807-817
[10]   Primary T cell expansion and requires antigen presentation differentiation in vivo by B cells [J].
Crawford, Alison ;
MacLeod, Megan ;
Schumacher, Ton ;
Corlett, Louise ;
Gray, David .
JOURNAL OF IMMUNOLOGY, 2006, 176 (06) :3498-3506