*Purpose: Until now, no blood biomarkers have been identified to enable early diagnosis of acute cellular or chronic active antibody-mediated rejection (cABMR) after pediatric kidney transplantation. As rejection episodes are associated with an adoption of B- and T-cellular immunity, changes in associated plasma cytokines can be expected. Blood samples from 51 pediatric kidney transplant patients were analysed for interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17A, TNFα und IFNγ by flow cytometric analysis at time of renal protocol biopsy 6 months after transplantation or biopsy-of-cause. In the cohort, 17 children were diagnosed with acute cellular rejection Banff ≥ IA and 14 children with biopsy-proven cABMR whereas all other children had normal protocol biopsies. The patients were divided into a training (n=34) and a validation (n=17) set.

*Methods: Blood samples from 51 pediatric kidney transplant patients were analysed for interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17A, TNFα und IFNγ by flow cytometric analysis at time of renal protocol biopsy 6 months after transplantation or biopsy-of-cause. In the cohort, 17 children were diagnosed with acute cellular rejection Banff ≥ IA and 14 children with biopsy-proven cABMR whereas all other children had normal protocol biopsies. The patients were divided into a training (n=34) and a validation (n=17) set.

*Results: In patients with acute cellular rejection Banff ≥ IA (training set), IL-6 concentration (3720 SD 3095 vs. 825 SD 629 fg/ml, p = 0.0009) and IL-10 concentration (2448 SD 5369 vs. 504 SD 939 fg/ml, p = 0.05) were significantly higher than in the other patients. In children with cABMR IL-6 (552 SD 653 vs. 1644 SD 1453 fg/ml, p = 0.01) but not IL-10 concentration was significantly lower. Among patients with increase of s-creatinine, IL-6 values (3720 SD 3059 vs. 552 SD 453 fg/ml, p = 0.00013) but not IL-10 values were significantly different between patients with acute cellular rejection and cABMR. For IL-2, IL-4, IL-17A, TNFα and IFNγ no differences were found between the groups. In the independent validation cohort, acute cellular rejection and cAMR showed an area under the receiver operating characteristic curve for IL-6 of 0.79 and 0.81, respectively. In children with acute cellular rejection IL-6 > 2100 fg/ml and in those with cAMR IL-6 < 700 fg/ml were associated with a specificity of 75% / 77%, a sensitivity of 83% / 60%, a positive predictive value of 62% / 50% and a negative predictive value of 90% / 83%.

*Conclusions: Plasma IL-6 and IL-10 levels are promising biomarkers to identify pediatric kidney transplant recipients free from acute cellular and chronic antibody mediated rejection who might not need a graft biopsy. Validation in larger cohorts and combination with other biomarkers are warranted.

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