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

• Published in: Diabetes (New York, N.Y.) Vol. 58; no. 10; pp. 2267 - 2276
• Main Authors: HILBRANDS, Robert, HUURMAN, Volkert A. L, JACOBS-TULLENEERS-THEVISSEN, Daniel, MONBALIU, Diethard, YSEBAERT, Dirk, GORUS, Frans K, ROEP, Bart O, PIPELEERS, Daniel G, KEYMEULEN, Bart, GILLARD, Pieter, VELTHUIS, Jurjen H. L, DE WAELE, Marc, MATHIEU, Chantal, KAUFMAN, Leonard, PIPELEERS-MARICHAL, Miriam, ZHIDONG LING, MOVAHEDI, Babak
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-10-2009
• Subjects: Adult; Antibodies; Anticoagulants; Anticoagulants - therapeutic use; Antilymphocyte Serum - therapeutic use; Biological and medical sciences; Biopsy; C-Peptide - blood; C-Peptide - deficiency; Care and treatment; Diabetes; Diabetes Mellitus, Type 1 - surgery; Diabetes. Impaired glucose tolerance; Diabetics; Drug Therapy, Combination; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Health aspects; Humans; Immunosuppressive Agents - therapeutic use; Induction therapy; Insulin; Insulin - metabolism; Insulin-Secreting Cells - physiology; Islet cell transplantation; Islets of Langerhans Transplantation - immunology; Liver - pathology; Lymphocyte Count; Lymphocytes; Male; Measurement; Medical examination; Medical sciences; Metabolism; Middle Aged; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - therapeutic use; Original; Patient outcomes; Patients; Peptides; Physiological aspects; Reference Values; Reoperation - statistics & numerical data; Research design; Serology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Tacrolimus - therapeutic use; Transplants & implants; Treatment Outcome; Type 1 diabetes; Belgium; Endocrinopathy; Human; Immunopathology; Type 1 diabetes; Autoimmune disease; Transplantation; Lymphocyte
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db09-0160

Differences in Baseline Lymphocyte Counts and Autoreactivity Are Associated With Differences in Outcome of Islet Cell Transplantation
in Type 1 Diabetic Patients
Robert Hilbrands 1 , 2 ,
Volkert A.L. Huurman 2 , 3 ,
Pieter Gillard 1 , 2 , 4 ,
Jurjen H.L. Velthuis 2 , 3 ,
Marc De Waele 1 ,
Chantal Mathieu 2 , 4 ,
Leonard Kaufman 5 ,
Miriam Pipeleers-Marichal 1 ,
Zhidong Ling 1 , 2 ,
Babak Movahedi 1 , 2 ,
Daniel Jacobs-Tulleneers-Thevissen 1 , 2 ,
Diethard Monbaliu 6 ,
Dirk Ysebaert 7 ,
Frans K. Gorus 1 , 2 ,
Bart O. Roep 2 , 3 ,
Daniel G. Pipeleers 1 , 2 and
Bart Keymeulen 1 , 2
1 Diabetes Research Center and Universitair Ziekenhuis Brussels, Brussels Free University-Vrije Universiteit Brussel (VUB),
Brussels, Belgium;
2 Juvenile Diabetes Research Foundation Center for β-Cell Therapy in Diabetes, Brussels, Belgium;
3 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands;
4 Department of Endocrinology, Universitair Ziekenhuis Gasthuisberg, Catholic University of Leuven, Leuven, Belgium;
5 Department of Biostatistics, Brussels Free University-VUB, Brussels, Belgium;
6 Department of Surgery, Universitair Ziekenhuis Gasthuisberg, Catholic University of Leuven, Leuven, Belgium;
7 Department of Surgery, Universitair Ziekenhuis Antwerpen, University of Antwerp, Antwerp, Belgium.
Corresponding author: Bart Keymeulen, bart.keymeulen{at}uzbrussel.be .
R.H. and V.A.L.H. contributed equally to this article.
Abstract
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 β-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.
Footnotes
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Clinical trial reg. no. NCT00623610, clinicaltrials.gov .
See accompanying commentary, p. 2187 .
Received February 9, 2009.
Accepted July 7, 2009.
© 2009 by the American Diabetes Association.