Alloimmune Monitoring After Islet Transplantation: A Prospective Multicenter Assessment of 25 Recipients.
Islet transplantation is an effective treatment for selected patients with type 1 diabetes. However, an accurate test still lacks for the early detection of graft rejection. Blood samples were prospectively collected in four university centers (Geneva, Grenoble, Montpellier, and Strasbourg). Peripheral blood mononuclear cells were stimulated with donor splenocytes in the presence of interleukin-2. After 24 h of incubation, interferon- (IFN-) ELISpot analysis was performed. After a total of 5 days of incubation, cell proliferation was assessed by fluorescence-activated cell sorting (FACS) analysis for Ki-67. Immunological events were correlated with adverse metabolic events determined by loss of 1 point of -score and/or an increased insulin intake 10%. Twenty-five patients were analyzed; 14 were recipients of islets alone, and 11 combined with kidney. Overall, 76% (19/25) reached insulin independence at one point during a mean follow-up of 30.7 months. IFN- ELISpot showed no detectable correlation with adverse metabolic events [area under the curve (AUC)=0.57]. Similarly, cell proliferation analysis showed no detectable correlation with adverse metabolic events (CD3+/CD4+ AUC=0.54; CD3+/CD8+ AUC=0.55; CD3/CD56+ AUC=0.50). CD3/CD56+ cell proliferation was significantly higher in patients with combined kidney transplantation versus islet alone (6 months, p=0.010; 12 months, p=0.016; and 24 months, p=0.018). Donor antigen-stimulated IFN- production and cell proliferation do not predict adverse metabolic events after islet transplantation. This suggests that the volume of transplanted islets is too small to produce a detectable systemic immune response and/or that alloimmune rejection is not the sole reason for the loss of islet graft function.
Vaihere
V
Delaune
Christian
C
Toso
Pierre-Yves
PY
Benhamou
Anne
A
Wojtusciszyn
Laurence
L
Kessler
Florence
F
Slits
Sandrine
S
Demuylder-Mischler
Nadine
N
Pernin
Sandrine
S
Lablanche
Lorenzo A
LA
Orci
Graziano
G
Oldani
Philippe
P
Morel
Thierry
T
Berney
Stphanie
S
Lacotte
D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D005260:Female; D006801:Humans; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies