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<p>Deterioration of renal allograft function, either due to allograft rejection or calcineurin inhibitor toxicity (CNIT), requires prompt diagnosis to improve the graft function. However, its current estimation through serum creatinine or histological evaluation may not detect the subclinical changes and has certain limitations. Hence, identification of biomarkers that predicts allograft injury would be of great importance for the better management of renal allograft. In this study, we assessed the potential use of specific immune regulatory and inflammatory genes as predictive biomarkers for allograft rejection and CNIT. In this prospective longitudinal cohort study, 40 live-related kidney transplant recipients were enrolled, and their peripheral blood was assessed for the mRNA expression of the genes B-cell scaffold protein with ankyrin repeats 1 (<i>BANK1</i>), Forkhead Box Protein 3 (<i>FOXP3</i>), C-X-C-motif ligand 9 (<i>CXCL9</i>), C-X-C-motif ligand 10 (<i>CXCL10</i>), <i>Granzyme B</i>, and RAR-related orphan receptor gamma (<i>RORC</i>) at three time points namely pre-transplant, first-month post-transplant, and third-month post-transplant. All patients had minimum clinical follow-up of 24&#xa0;months, and comprehensive histopathological examination of indication graft biopsies were correlated with biomarker levels for predictive capability. A Receiver Operating Characteristic (ROC) curve was used to assess the predictive ability of these genes as biomarkers. Allograft rejection was observed in 34.21% of recipients, whereas 57.89% exhibited hCNIT and 15.79% had both allograft rejection and CNIT. The pre-transplant levels of the genes <i>BANK1</i> and <i>FOXP3</i> were able to predict recipients at the risk of post-transplant allograft rejection with an Area Under the Curve (AUC) of 0.87 (<i>p</i> &lt; 0.05), and the genes <i>BANK1</i> and <i>RORC</i> were able to predict recipients at the risk of CNIT with an AUC of 0.74 (<i>p</i> &lt; 0.05). This study highlights the potential of pre-transplant expression of the <i>BANK1</i>, <i>FOXP3</i>, and <i>RORC</i> as minimally invasive genetic biomarkers for predicting allograft rejection and CNIT.</p>

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Association of immune regulatory and inflammatory genes with histological injuries in renal allograft biopsies and their assessment as predictive biomarker for allograft injury in kidney transplant recipients

  • 期刊论文

  • 发表日期：

    2025年4月17日

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  • C. Priscilla,
  • Santosh Kumar,
  • Srinivas Nagaram,
  • Sreejith Parameswaran,
  • Pragasam Viswanathan,
  • Rajesh Nachiappa Ganesh

摘要

Deterioration of renal allograft function, either due to allograft rejection or calcineurin inhibitor toxicity (CNIT), requires prompt diagnosis to improve the graft function. However, its current estimation through serum creatinine or histological evaluation may not detect the subclinical changes and has certain limitations. Hence, identification of biomarkers that predicts allograft injury would be of great importance for the better management of renal allograft. In this study, we assessed the potential use of specific immune regulatory and inflammatory genes as predictive biomarkers for allograft rejection and CNIT. In this prospective longitudinal cohort study, 40 live-related kidney transplant recipients were enrolled, and their peripheral blood was assessed for the mRNA expression of the genes B-cell scaffold protein with ankyrin repeats 1 (BANK1), Forkhead Box Protein 3 (FOXP3), C-X-C-motif ligand 9 (CXCL9), C-X-C-motif ligand 10 (CXCL10), Granzyme B, and RAR-related orphan receptor gamma (RORC) at three time points namely pre-transplant, first-month post-transplant, and third-month post-transplant. All patients had minimum clinical follow-up of 24 months, and comprehensive histopathological examination of indication graft biopsies were correlated with biomarker levels for predictive capability. A Receiver Operating Characteristic (ROC) curve was used to assess the predictive ability of these genes as biomarkers. Allograft rejection was observed in 34.21% of recipients, whereas 57.89% exhibited hCNIT and 15.79% had both allograft rejection and CNIT. The pre-transplant levels of the genes BANK1 and FOXP3 were able to predict recipients at the risk of post-transplant allograft rejection with an Area Under the Curve (AUC) of 0.87 (p < 0.05), and the genes BANK1 and RORC were able to predict recipients at the risk of CNIT with an AUC of 0.74 (p < 0.05). This study highlights the potential of pre-transplant expression of the BANK1, FOXP3, and RORC as minimally invasive genetic biomarkers for predicting allograft rejection and CNIT.