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Titolo:
Novel approaches toward early diagnosis of islet allograft rejection
Autore:
Shapiro, AMJ; Hao, EG; Lakey, JRT; Yakimets, WJ; Churchill, TA; Mitlianga, PG; Papadopoulos, GK; Elliott, JF; Rajotte, RV; Kneteman, NM;
Indirizzi:
Univ Alberta, Dept Surg, Surg Med Res Inst, Edmonton, AB, Canada Univ Alberta Edmonton AB Canada Surg Med Res Inst, Edmonton, AB, Canada Univ Alberta, Dept Med Microbiol & Immunol, Edmonton, AB, Canada Univ Alberta Edmonton AB Canada icrobiol & Immunol, Edmonton, AB, Canada Technol Educ Inst Epirus, Biochem & Biophys Lab, Epirus, Greece Technol Educ Inst Epirus Epirus Greece em & Biophys Lab, Epirus, Greece
Titolo Testata:
TRANSPLANTATION
fascicolo: 12, volume: 71, anno: 2001,
pagine: 1709 - 1718
SICI:
0041-1337(20010627)71:12<1709:NATEDO>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLUTAMIC-ACID DECARBOXYLASE; DEPENDENT DIABETES-MELLITUS; BETA-GALACTOSIDASE; PANCREATIC-ISLETS; KIDNEY TRANSPLANTATION; PERCUTANEOUS BIOPSY; FAS LIGAND; IN-VITRO; INSULIN; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
66
Recensione:
Indirizzi per estratti:
Indirizzo: Shapiro, AMJ Univ Alberta Hosp, Mackenzie Hlth Sci Ctr, Dept Surg 2D4 37, Surg Med Res Inst, 8440-112 St, Edmonton, AB T6G 2B7, Canada Univ Alberta Hosp 8440-112 St Edmonton AB Canada T6G 2B7 nada
Citazione:
A.M.J. Shapiro et al., "Novel approaches toward early diagnosis of islet allograft rejection", TRANSPLANT, 71(12), 2001, pp. 1709-1718

Abstract

Background. The inability to diagnose early rejection of an islet allograft has previously proved to be a major impediment to progress in clinical islet transplantation. The need to detect early rejection will become even more relevant as new tolerance-inducing protocols are evaluated in the clinic. We explored three novel approaches toward development of early diagnosticmarkers of islet rejection after islet allotransplantation. Methods. (a) Canine islet allograft transplant recipients were immunosuppressed for 1 month, then therapy was withdrawn, Serum glutamic acid decarboxylase antigen (GAD(65)), an endogenous islet protein, was monitored daily with a CO2 release assay. (b) Rodent islets were genetically engineered to express a unique foreign protein (beta -galactosidase) by using adenoviral vectors, and after allograft transplantation, the viral-specific protein wasmeasured in serum using optical luminescence. (c) Rodents receiving islet allografts were immunosuppressed temporarily, and daily glucose tolerance tests were followed until graft failure occurred. Results. (a) Although serum monitoring of GAD(65) antigen demonstrated elevated levels preceding loss of graft function in preliminary studies, the effect was not reproducible in all animals. (b) Genetically engineered rodent islets demonstrated normal insulin kinetics in vitro (insulin stimulationindex 2.57+/-0.2 vs. 2.95+/-0.3 for control islets, P=ns), and purified viral protein products had a stable half-life of 8 hr in vivo. After islet allotransplantation, there were two peak elevations in serum viral proteins, confirming that an intra-islet "sentinel signal" could be detected serologically during acute rejection. There was no lead-time ahead of hyperglycemia, however. (c) Daily sequential intravenous glucose tolerance (IVGT) tests demonstrated evidence of allograft dysfunction (decline in K-G) with a 2-day lead time to hyperglycemia (2.58+/-0.3 vs. 1.63+/-0.2%/min, respectively,P<0.001), with an accuracy of 89%, sensitivity of 78%, and specificity of 95%. Conclusions. Of the three diagnostic tests, metabolic assessment with an abbreviated IVGT was the most effective method of demonstrating early islet dysfunction due to rejection.

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Documento generato il 04/04/20 alle ore 11:06:36