Differences in baseline lymphocyte counts and autoreactivity are associated with differences in outcome of islet cell transplantation in type 1 diabetic patients.
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.


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 beta-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.
Hilbrands
Robert
R
Diabetes Research Center and Universitair Ziekenhuis Brussels, Brussels Free University-Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Huurman
Volkert A L
VA
Gillard
Pieter
P
Velthuis
Jurjen H L
JH
De Waele
Marc
M
Mathieu
Chantal
C
Kaufman
Leonard
L
Pipeleers-Marichal
Miriam
M
Ling
Zhidong
Z
Movahedi
Babak
B
Jacobs-Tulleneers-Thevissen
Daniel
D
Monbaliu
Diethard
D
Ysebaert
Dirk
D
Gorus
Frans K
FK
Roep
Bart O
BO
Pipeleers
Daniel G
DG
Keymeulen
Bart
B
D000328:Adult; D000925:Anticoagulants / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001706:Biopsy; D002096:C-Peptide / Q000097:blood / Q000172:deficiency; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008099:Liver / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D012016:Reference Values; D012086:Reoperation / Q000706:statistics & numerical data; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome
D000925:Anticoagulants; D000961:Antilymphocyte Serum; D002096:C-Peptide; D007166:Immunosuppressive Agents; D007328:Insulin; D009173:Mycophenolic Acid; D016559:Tacrolimus