Background: Despite current therapy, antibody mediated rejection (AMR) remains a major cause of kidney allograft loss. IL-6 is a known survival factor of antibody secreting plasma cells, a major effector of AMR, and a major pro inflammatory cytokine. However, the role of IL-6 in AMR is currently unknown.

Methods: This is a prospective single center study of patients with biopsy proven AMR (BANFF 2013) between 10/14 and 9/15. Peripheral blood and kidney biopsy tissue were collected at 2 time points: 1) at the diagnosis of AMR and 2) after treatment. Immune profiling (peripheral blood immune subsets and cytometric bead array) of patients with AMR was undertaken by flow cytometry and compared to healthy controls.

Results: 4 patients had biopsy proven antibody mediated rejection over the study period (mean C4d score 2.8 ± 0.5 and mean microvascular injury score 3.0 ± 1.2). 3 out of 4 patients were found to have resolution of AMR on post treatment biopsy. Patients that responded to treatment had a reduction in peripheral IL-6 levels (3.3 ± 1.1 pg/ml) as well as a reduction in peripheral B-lymphocyte and plasma cell numbers (201.8 ± 552.3 cells/uL and 33.4 ± 58.3 cells/uL, respectively). There was no clear association with response to treatment for other cytokines tested (IL-2, IL-4, IL-17, TNF, IFNg, APRIL, and BLyS) and other peripheral cell subsets tested (T-lymphocyte, NK cells, CD14+ cells). Additionally, compared to healthy controls, patients with AMR had an increase in IL-6 in peripheral blood (4.1 ± 1.1 pg/ml compared to 1.3 ± 0.76 g/ml, respectively).

Conclusions: Compared to healthy controls, IL-6 was elevated in kidney transplant patients with AMR. In patients who responded to treatment for AMR, a reduction of IL-6 levels was observed. Given the known role of IL-6 as a major survival factor for alloantibody secreting cells, IL-6 may serve as both an important indicator for therapeutic response to treatment, and may serve as an additional target for treatment of AMR.

CITATION INFORMATION: Wilson N, Djamali A, Redfield R. Elevation of Peripheral IL-6 in Kidney Transplant Recipients with Antibody Mediated Rejection. Am J Transplant. 2016;16 (suppl 3).

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