Alloreactivity against repeated HLA mismatches of sequential islet grafts transplanted in non-uremic type 1 diabetes patients.
BACKGROUND
Islet transplantation can restore insulin production in type 1 diabetes patients. However, survival of the islet allografts will face rejection or recurrence of autoimmunity or a combination of both. In a study on islet-after-kidney transplants, we previously reported that islet cell recipients presented low T-cell alloresponses for HLA mismatches that were shared by the islet cell graft and the prior kidney graft, that is, repeated mismatch, while vigorous responses were measured against novel HLA mismatches.


METHODS
We now investigated T-cell alloreactivity to repeated HLA-mismatches in three non-uremic type 1 diabetic patients each receiving three sequential islet cell implants.


RESULTS
These islet-after-islet recipients patients exhibited low or absent responses to repeated mismatches to the first graft which was accompanied by sustained graft function, and reduced responsiveness towards subsequent grafts. In one patient, T-cell responses towards these mismatches were noticed following new mismatches in subsequent grafts, with loss of graft function.


CONCLUSIONS
These case reports further support the view that subsequent islet implantations can reduce alloreactivity for repeated HLA mismatches. They demonstrate the usefulness of monitoring T-cell reactivity against islet allografts to correlate immune function with graft survival and to identify conditions for preservation of beta-cell function.
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Corine A
CA
van Kampen
Pieter
P
van de Linde
Gaby
G
Duinkerken
Jolien J
JJ
van Schip
Dave L
DL
Roelen
Bart
B
Keymeulen
Daniel G
DG
Pipeleers
Frans H J
FH
Claas
Bart O
BO
Roep
D000961:Antilymphocyte Serum / Q000627:therapeutic use; D015551:Autoimmunity; D002096:C-Peptide / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D006085:Graft Survival / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000502:physiology; D007518:Isoantibodies / Q000097:blood; D011184:Postoperative Period; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous / Q000276:immunology; D014511:Uremia
D000961:Antilymphocyte Serum; D002096:C-Peptide; D007166:Immunosuppressive Agents; D007518:Isoantibodies