Selective unresponsiveness to beta cell autoantigens after induction immunosuppression in pancreas transplantation with anti-interleukin-2 receptor antibody versus anti-thymocyte globulin.
Pancreas transplantation in type 1 diabetes patients could result in (re)activation of allo- and autoreactive T lymphocytes. Anti-thymocyte globulin (ATG) induction treatment is a successful, but broadly reactive anti-lymphocyte therapy used in pancreas and islet transplantation. A more selective alternative is daclizumab, a monoclonal antibody directed against the interleukin-2 receptor (CD25) on activated lymphocytes. We tested the hypothesis that daclizumab is more selective and has less immunological side effects than ATG. Thirty-nine simultaneous pancreas-kidney transplantation patients with type 1 diabetes were randomized for induction therapy with ATG or daclizumab. Auto- and recall immunity was measured cross-sectionally by lymphocyte stimulation tests with a series of auto- and recall antigens in 35 successfully transplanted patients. T cell autoimmunity to islets was low in both groups, except for a marginal but significantly higher reactivity against glutamic acid decarboxylase (GAD)65 in daclizumab-treated patients. The memory responses to recall antigens were significantly higher in the daclizumab-treated group compared to ATG-treated patients, specifically against purified protein derivative (PPD) (anti-bacterial immunity), Haemophilus influenzae virus matrix protein-1 (anti-viral immunity) and p53 [anti-tumour (auto)immunity]. These data imply that daclizumab is more specifically affecting diabetes-related immune responses than ATG. The autoimmunity is affected effectively after daclizumab induction, while memory responses towards bacterial, viral and tumour antigens are preserved.
van de Linde
P
P
Department of Surgery, LUMC, Leiden, The Netherlands.
Vd Boog
P J M
PJ
Tysma
O M H
OM
Elliott
J F
JF
Roelen
D L
DL
Claas
F H J
FH
de Fijter
J W
JW
Roep
B O
BO
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001324:Autoantigens / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D000077561:Daclizumab; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000601:surgery*; D005260:Female; D006084:Graft Rejection / Q000628:therapy; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000627:therapeutic use; D007156:Immunologic Memory; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D001324:Autoantigens; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D000077561:Daclizumab