High levels of IDO-expressing CD16+ peripheral cells, and Tregs in graft biopsies from kidney transplant recipients under belatacept treatment.

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme that suppresses T-lymphocyte activity. Costimulation blockade through CTLA4lg increases IDO in antigen-presenting cells. The suppressive effect of IDO is thought to be mediated by Foxp3+CD4+CD25+ regulatory T-cells (Tregs). OBJECTIVE: In this descriptive study, we evaluated the percentage of IDO-expressing peripheral cell subpopulations as well as Tregs in 27 stable kidney transplant recipients receiving either belatacept (LEA29Y), a daughter compound of abatacept (CTLA4lg; n = 19) or cyclosporine (n = 8). METHODS: Blood samples were obtained at 24 ± 2 months (belatacept) and 23 ± 6 months (cyclosporine) of treatment. Intracellular IDO was analyzed by flow cytometry in CD14+, CD11c+, CD16+, CD56+, and CD8+ cell subpopulations. Tregs were assessed by intracellular Foxp3 detection in CD4+CD25+ cells. CD3+, CD4+, CD8+, CD20+, CD68+, IDO+, and Foxp3+ cells were evaluated by immunohistochemistry on graft biopsies obtained preimplantation, at 12 months posttransplant, and in subjects with dysfunction during the first 12 months. RESULTS: Only percentages of CD16+/IDO+-expressing peripheral monocytes were significantly increased among the group receiving belatacept. No differences were observed in peripheral Tregs between the groups. In contrast, higher percentages of Tregs, CD4+, CD8+, and CD68+ cells were noted in dysfunction and at 12 months vs baseline among graft biopsies in subjects receiving belatacept, and also among dysfunction cohorts of belatacept vs Cyclosporine treatment. CONCLUSION: Patients receiving belatacept showed greater amounts of peripheral blood CD16+/IDO+ cells and Tregs on graft biopsies than those under cyclosporine treatment.

Prevalence of HLA antibodies and its impact on graft function in a group of kidney transplant recipients: a cross-sectional study.

UNLABELLED: HLA alloantibodies (Abs) are associated with chronic rejection and poorer graft survival. The current study was designed to document the prevalence of HLA Abs in a group of kidney transplant recipients (KTR) and its impact on graft function. PATIENTS AND METHODS: 283 KTR transplanted between January 1990 and December 2003 who had a functional graft were invited to participate. 198 KTR were enrolled. HLA class I and II Abs were measured by Luminex-One Lambda. Graft function was assessed by DeltaCr and GFR calculated by the Levey formula. RESULTS: Median post-kidney transplant (post-KT) follow-up was 51.4 (4.3 to 176.3) months. Forty-four (22.2%) KTR were found to have class I and/or class II Abs. Eleven had both class I and II Abs, ten were positive only for class I, and 23 for class II. Overall, no significant difference was seen in renal function. The DeltaCr for Ab positive and Ab negative were -0.24+/-0.84 and -0.17+/-0.60 mg/dL (P=0.54), respectively. The GFR for Ab positive and Ab negative were 64.4+/-26 and 60.2+/-20 mL/min (P=0.25), respectively. No statistically significant difference was found between HLA Abs and number of HLA mismatches, gender, blood transfusions, pre-KT pregnancies, DGF, history of acute rejection, and chronic allograft nephropathy. Adjusting analysis by transplant year showed no significant difference. CONCLUSION: The prevalence of HLA antibodies was similar to previous reports. In this cross-sectional study, the presence of HLA antibodies was not related to a negative impact on renal function.