4.7 Article

Urinary Exosomal Cystatin C and Lipopolysaccharide Binding Protein as Biomarkers for Antibody-Mediated Rejection after Kidney Transplantation

Journal

BIOMEDICINES
Volume 10, Issue 10, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines10102346

Keywords

kidney transplant; biomarker; exosome; urine; antibody-mediated rejection; Cystatin C; lipopolysaccharide binding protein

Funding

  1. Ministry of Science & ICT of the Republic of Korea [2016M3A9E8941330]
  2. Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea [2018-619]
  3. National Research Foundation of Korea [2016M3A9E8941330] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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This study aimed to identify and validate urinary exosomal proteins as biomarkers for antibody-mediated rejection (ABMR) after kidney transplantation. Through proteomic analysis, four specific proteins associated with ABMR were discovered. In the validation cohort, the levels of these proteins were significantly higher in the ABMR group compared to other groups. Immunohistochemical staining showed that these proteins were more abundant in the glomerulus of the ABMR group. The combined prediction probability of these urinary exosomal proteins was significantly correlated with the scores in the glomerulus and peritubular capillary, as well as the Banff g + ptc scores.
We aimed to discover and validate urinary exosomal proteins as biomarkers for antibody-mediated rejection (ABMR) after kidney transplantation. Urine and for-cause biopsy samples from kidney transplant recipients were collected and categorized into the discovery cohort (n = 36) and a validation cohort (n = 65). Exosomes were isolated by stepwise ultra-centrifugation for proteomic analysis to discover biomarker candidates for ABMR (n = 12). Of 1820 exosomal proteins in the discovery cohort, four proteins were specifically associated with ABMR: cystatin C (CST3), serum paraoxonase/arylesterase 1, retinol-binding protein 4, and lipopolysaccharide-binding protein (LBP). In the validation cohort, the level of urinary exosomal LBP was significantly higher in the ABMR group (n = 25) compared with the T-cell-mediated rejection (TCMR) group and the no major abnormality (NOMOA) group. Urinary exosomal CST3 level was significantly higher in the ABMR group compared with the control and NOMOA groups. Immunohistochemical staining showed that LBP and CST3 in the glomerulus were more abundant in the ABMR group compared with other groups. The combined prediction probability of urinary exosomal LBP and CST3 was significantly correlated with summed LBP and CST3 intensity scores in the glomerulus and peritubular capillary as well as Banff g + ptc scores. Urinary exosomal CST3 and LBP could be potent biomarkers for ABMR after kidney transplantation.

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