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Войти в исследования Translational andrology and urology · 2026
DDR2 expression on circulating lymphocytes and monocytes associates with chronic active antibody-mediated rejection in kidney transplant recipients.
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Li Guanghui, Liu Luhao, Hu Yuyang, Guo Yuhe, Wan Jiao, Fang Jiali, Su Jin, Chen Zheng
Аннотация
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.
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.