Introduction: In the intricate symphony of molecular orchestration within the human body, microRNAs (miRNAs) are master conductors, deftly guiding essential biological processes like immune response, inflammation, and tissue repair. Among these virtuosos, miR-142-5p and miR-192-1 emerge as stars, their melodies resonating profoundly in renal transplant pathology. Our study endeavors to unravel the complex roles they play in the delicate dance between MIR-142-5p and miR-192-1 in the fate of renal transplants.
Methods: The study assessed plasma expression levels of specific microRNAs (miRNAs) using quantitative real-time PCR in a cohort of 100 kidney transplant recipients. This cohort comprised individuals with long-term stable allograft function without acute rejection (AR) (n = 29), those with T-cell-mediated rejection (TCMR) (n = 16), those with antibody-mediated rejection (ABMR) (n = 28), and those with mixed rejection involving both TCMR and ABMR (n = 27). Additionally, the potential correlation between histological parameters and circulating miRNAs was examined. The incidence of diffuse (>50%) interstitial fibrosis (IF) in subsequent biopsies was also evaluated as part of the follow-up protocol.
Results: Significantly upregulated expressions of miR-142-5p (p<0.001) and miR-192-1 (p<0.001) were observed in plasma samples of recipients with AR and IF development. Upregulated miR-142-5p and miR-192-1 were significantly associated with interstitial inflammation, eosinophil and plasma infiltration, peritubular capillary (PTC) C4d expression, PTC inflammation, PTC destruction, glomerulitis, number of AR episode, vascular rejection, thrombotic microangiopathy, tubular HLA-DR expression, average time of the IF development, and graft loss. The overall 5-year risk of IF development was 23% and 52% for patients with low and high miR-142-5p, respectively (p=0.002). It was 21% and 57% for recipients with low and high miR-192-1, respectively (p<0.001). The overall 5-year graft survival was 94% and 64% for cases with low and high miR-142-5p, respectively (p=0.001). It is 93% and 61% for patients with low and high miR-192-1, respectively (p<0.001).
Conclusion: Our study underscores the significant involvement of miR-142-5p and miR-192-1 in renal transplant pathology, particularly in AR and IF processes. Additionally, the study reveals a correlation between circulating microRNAs and AR type, inflammation, and microvascular injury. Overall, these findings suggest that these microRNAs have the potential to serve as accessible biomarkers for monitoring AR and IF, along with microvascular injury status in AR and related pathologies.