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. (28th September 2017)

• Record Type: Journal Article
• Authors: Désy, Olivier; Béland, Stéphanie; Vallin, Patrice; Riopel, Julie; Latulippe, Eva; Najafian, Nader; Chandraker, Anil; Agharazii, Mohsen; Batal, Ibrahim; De Serres, Sacha A.
• Is Part Of: Transplant international. Volume 31:Number 1(2018)
• Page Start: 92
• Page End: 101
• Publication Date: 2017-09-28
• Subjects: acute rejection -- chronic inflammation -- cytokines -- macrophages -- renal transplantation; Transplantation of organs, tissues, etc -- Periodicals; 617.95405
• DOI: 10.1111/tri.13070
• Languages: English
• ISSNs: 0934-0874

Abstract

Summary: 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.