IL-6 production by monocytes is associated with graft function decline in patients with borderline changes suspicious for acute T-cell-mediated rejection: a pilot study
Transplant International | September 14, 2017
Désy O, Béland S, Vallin P, Riopel J, Latulippe E, Najafian N, Chandraker A, Agharazii M, Batal I and De Serres SA
Transpl Int. 2018;31:92-101
Although borderline changes (BL) suspicious for acute T-cell-mediated rejection represent a diagnostic category, its clinical relevance is questioned leading to heterogeneous therapeutic management. We hypothesized that measuring IL-6 secretion by peripheral blood mononuclear cells identifies patients with ongoing graft damage. We examined the association between secreted IL-6 and the change in estimated glomerular filtration rate at 6 months after the biopsy (ΔeGFR). We then conducted phenotypic and functional studies on patient and mouse innate immune cells in the blood and the kidney. In a training set, ΔeGFR was strongly associated with IL-6 levels, showing a clinically meaningful decline of 4.6 ± 1.5 ml/min per increase in log10 IL-6 (P = 0.001). These results were consistent after adjustment and were reproduced in a validation cohort. Phenotyping of peripheral blood cells revealed that the main source of IL-6 was CD14+CD16−CCR2+HLA-DR+CD86+CD11c+ inflammatory monocytes. There was a significant correlation between IL-6 secretion and interstitial dendritic cell density in the biopsy. Finally, characterization of mouse kidney dendritic cells revealed that they share features with macrophages and function as effector cells secreting IL-6. In conclusion, measuring IL-6 secreted by peripheral blood cells can be useful in the management of patients with BL in the absence of a concurrent inflammatory condition.