A Molecular Signature of Two Long Non-Coding RNAs in Peripheral Blood Predicts Acute Renal Allograft Rejection

Abstract

Background/Aims: Acute rejection (AR) is a major complication post renal transplantation, with no widely-accepted non-invasive biomarker. This study aimed to explore the expression profiles of long non-coding RNAs (lncRNAs) in the peripheral blood (PB) of renal transplant recipients and their potential diagnostic values. Methods: The genome-wide lncRNA expression profiles were analyzed in 150 PB samples from pediatric and adult renal transplant (PRTx and ARTx) cohorts. The diagnostic performance of differentially expressed lncRNA was determined using receiver operator characteristic curve, with area under the curve (AUC) and 95% confidential interval (CI). Finally, a risk score was constructed with logistical regression model. Results: A total of 162 lncRNAs were found differentially expressed in PRTx cohort, while 163 in ARTx cohort. Among these identified lncRNAs, 23 deregulated accordingly in both cohorts, and could distinguish AR recipients from those without AR. Finally, a risk score with two most significant lncRNAs (AF264622 and AB209021) was generated and exhibited excellent diagnostic performance in both PRTx (AUC:0.829, 95% CI:0.735-0.922) and ARTx cohorts (AUC: 0.889, 95% CI: 0.817-0.960). Conclusion: A molecular signature of two lncRNAs in PB could serve as a novel non-invasive biomarker for the diagnosis of AR in both pediatric and adult renal transplant recipients.

Circulating Long Noncoding RNA LNC-EPHA6 Associates with Acute Rejection after Kidney Transplantation

“…However, here we analyzed four pre-selected lncRNAs, thus analyses of other lncRNAs in AR may yield additional associations and may potentially be important for prediction of (vascular injury after) AR. This is in line with two other studies that showed an association between lncRNAs and AR that suggested their value for diagnosis of AR in kidney transplantation [ 21 , 22 ]. Moreover, in a rat study, the lncRNA PRINS was shown to be significantly up-regulated in kidneys of rats with cold ischemia-elicited allograft rejection, compared with rats without rejection [ 23 ].…”

Endogenous intronic antisense long non-coding RNA, MGAT3-AS1, and kidney transplantation

“…Ge et al . showed that two LncRNAs, called AF264622 and AB209021, which were obtained in the peripheral blood cells, were increased in patients with acute kidney allograft rejection 10 . Another study indicated that urinary LncRNAs, called RP11-395P13.3-001 and RP11-354P17.15-001, were upregulated in patients with acute kidney allograft rejection 11 .…”

Diagnostic, Prognostic, and Therapeutic Value of Non-Coding RNA Expression Profiles in Renal Transplantation

“…AF264622 and AB209021 are two lncRNAs upregulated in peripheral blood from pediatric and adult renal transplant patients with AR. Their high sensitivity and specificity to detect AR make them a promising alternative in the search for non-invasive biomarkers of AR in both pediatric and adult renal transplant recipients [28].…”

“…Moreover, lncRNAs can interact with epigenetic regulators and transcription factors in a sequence-independent manner through non-coding transcription [5]. Multiple studies link lncRNA dysregulation and pathological disease states that affect the kidney, such as acute kidney injury (AKI), chronic kidney disease, nephropathies, and allograft rejection [27][28][29].…”