Background

Actually, a diagnosis of acute cellular or chronic humoral rejection after pediatric kidney transplantation (pKTX) can only be secured by graft biopsy. Until now, no blood biomarkers have been determined that enable early diagnosis of these two entities. As rejection episodes are associated with an adoption of B- and T-cellular immunity, changes in plasma cytokines can be expected.

Patients and method:

Heparinized blood samples from 34 pediatric kidney transplant patients were analyzed for interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17A, TNFa und IFNy by flow cytometric analysis at time of renal protocol biopsy (6 months after KTX) or indication biopsy. The results of 15 children with acute cellular rejection BANFF ≥ Iaand 8 children with biopsy proven chronic humoral rejection have been compared with those of 11 children with baseline creatinine and normal protocol biopsy.

Results:

In patients with acute rejection BANFF ≥ Ia, IL-6 concentration was significantly higher (median: 2518.25 fg/ml, range: 222.53-9282.54 fg/ml) than in the control group (median: 934.62 fg/ml, range 295.89-1723.95 fg/ml, p=0.01). In contrast, the IL-6 concentration in patients with chronic humoral rejection was significant decreased (median 390.95 fg/ml, range 53.9-868.83 fg/ml) compared to the control group (p=0.007) and to the patients with acute rejection (p =0.002). Measurements of IL-10 concentration showed the same tendency: increased IL-10 concentrations could be detected in patients with acute rejection (median 374.39 fg/ml, range: 62.89-18344.71 fg/ml, p=0.14) and decreased levels of IL-10 in patients with chronic humoral rejection (median: 185.86 fg/ml, range: 103.75-1074.91 fg/ml, p=0.79) compared to the control group (median 192.16 fg/ml, range 0.00-4411.19 fg/ml). For IL-2, IL-4, IL-17A, TNFa and IFNy, no differences could be detected between the groups.

Conclusion:

Cytokine-analysis in pediatric kidney recipients resulted in elevated levels for IL-6 and IL-10 in children with biopsy proven acute rejection BANFF ≥ Ia and in reduced levels in children with chronic humoral rejection as compared to controls. Therefore, Plasma IL-6 and IL-10 could be used as a biomarkers to substantiate suspicion of acute cellular and chronic humoral rejection and to support the decision making for a graft biopsy. The results will have to be validated in a larger cohort.

[LP1]Auch hier evtl .Kürzung: Klammer und Altersangaben.

CITATION INFORMATION: Ahlenstiel-Grunow T., Borsum N., Pape L. Cytokine Profiles in Children after Pediatric Kidney Transplantation with Acute and Chronic Rejection Am J Transplant. 2017;17 (suppl 3).

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