Subclinical inflammation in kidney allografts is associated with worse outcome and the activation of humoral alloimmunity. Surveillance allograft biopsies are an accurate tool to diagnose on-going inflammation but they are invasive and unsensitive. The T-cell ELISPOT assay has been shown to precisely predict cellular mediated rejection. Herein we investigated whether peripheral donor-specific T-cell (DSTc) alloreactivity is associated with the presence of subclinical inflammation (SCR) and can be an early predictive biomarker of subsequent activation of humoral responses.

82 consecutive low risk kidney transplant patients were evaluated with 6-month (6mo) surveillance biopsies using current Banff score classification and were followed for 24 months. DSTc alloreactivity was assessed during the first 6 months after transplantation using the IFN-g Elispot and presence of de novo anti-HLA alloantibodies (dnAbs) was investigated at 2 years.

At 6-month, 17/82(20.7%) clinically stable patients showed SCR (16 TCMR, 1 ABMR). Mean acute Banff scores were higher among SCR patients (at p=0.03, ai and ag p<0.01, ptc p=0.02, av p=0.58 and C4d p=0.03). Mean 12 and 24-month sCreat levels were significantly high in patients with 6mo SCR than those with normal biopsies (165.6±71 and 219.1±180.3 vs 133.8±48.8 and 131±36.5, p=0.04 and p<0.01). Circulating DSTc alloreactivity was found in 45/82(54.9%) patients and was associated with 6mo SCR (14/17 vs 3/17, p=0.01). At 24 months, 25/82(30.5%) showed dnAbs, being 11/82(13.4%) donor-specific (DSA). Patients with 24mo dnAbs displayed significantly higher incidence of 6mo SCR than patients without dnAbs (10/26 vs 7/49, p=0.007), showing higher ptc and ag scores than those without (0.33±0.5 and 0.48±0.9 vs 0.02±0.1 and 0.22±0.4, p=0.01 and p=0.09, respectively). Of note, 19/25 patients with dnAbs and 10/11 with 24mo DSA had showed DSTc alloreactivity during the first 6 months. Multivariate logistic analysis revealed that T-cell induction therapy, DSTc alloractivity and ptc score were independent predictors of dnAbs at 24mo (RR=1.13 CI95%0.17-7.3, p=0.05; RR=209 CI95%4.8-8954, p<0.01 and RR=0.19 CI95%0.04-0.8, p=0.03).

Cellular alloimmunity seems to precede humoral immunity activation early after transplantation and its monitoring might help to identify kidney transplant patients at risk of chronic humoral rejection.

CITATION INFORMATION: Crespo E, Luque S, Cruzado J, Melilli E, Grinyo J, Lucia M, Bestard O. Post-Transplant T-Cell Alloreactive Perturbation Precedes the Advent of Humoral Immunity in Kidney Transplant Patients. Am J Transplant. 2016;16 (suppl 3).

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