DDR2 expression on circulating lymphocytes and monocytes associates with chronic active antibody-mediated rejection in kidney transplant recipients.

BACKGROUND

Chronic antibody-mediated rejection (AMR) is a leading cause of late kidney allograft loss, yet sensitive non-invasive biomarkers are lacking. Discoidin domain receptor 2 (DDR2), a collagen-binding tyrosine kinase implicated in fibrosis, may play a role in its pathogenesis. This study aimed to investigate the expression and clinical relevance of DDR2 in patients with chronic AMR.

METHODS

In this single-center study, 76 renal transplant recipients were classified into a chronic active AMR group (n=31) based on Banff 2019 criteria and a control group with normal histology (n=45). DDR2 expression on peripheral blood lymphocytes and monocytes was quantified by flow cytometry. Associations between DDR2 levels and Banff lesion scores were analyzed.

RESULTS

Chronic AMR patients exhibited significantly higher proportions of DDR2+ lymphocytes (0.42%±0.42% vs. 0.21%±0.23%, P=0.008) and DDR2+ monocytes (1.22%±1.54% vs. 0.62%±0.57%, P=0.02). Using normal group mean + 2SD (standard deviation) threshold, 71.0% of AMR patients had elevated DDR2+ lymphocytes and 77.4% had elevated DDR2+ monocytes. DDR2+ lymphocyte percentages correlated with interstitial inflammation (i: ρ=0.41), C4d deposition (ρ=0.44), interstitial fibrosis (ci: ρ=0.48), tubular atrophy (ct: ρ=0.41), vascular intimal thickening (cv: ρ=0.43), and total inflammation (ti: ρ=0.48) (all P<0.05).

CONCLUSIONS

Upregulated DDR2 expression on circulating lymphocytes and monocytes is associated with biopsy-proven chronic AMR and correlates with key histopathological features of chronic allograft injury, particularly interstitial inflammation, fibrosis, and vasculopathy. These findings suggest DDR2 as a potential peripheral blood biomarker and a contributor to the pathophysiology of chronic AMR.