Bile: miRNA pattern and protein-based biomarkers may predict acute cellular rejection after liver transplantation

Schmuck, Rosa; Reutzel‐Selke, Anja; Raschzok, Nathanael; Morgül, Haluk; Struecker, Benjamin; Lippert, Steffen; Fischer, Cynthia De Carvalho; Schmelzle, Moritz; Boas-Knoop, Sabine; Bahra, Marcus; Pascher, Andreas; Pratschke, Johann; Sauer, Igor M.

doi:10.1080/1354750x.2016.1201538

Cited by 9 publications

(10 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Schmuck et al (27) CD44, CXCL19 ELISA -/45 ACR miR-122, miR-133a, miR-148a, and miR-194 qPCR Kim et al (28) APN Proteomics -/9 ACR Adams et al (29) ICAM1 ELISA -/61 ACR Adams et al (30) IL2R Unknown -/18 ACR Tono et al (31) IL6 ELISA 11/-ACR Umeshita et al (32) IL6 ELISA -/51 ACR Morimoto et al (33) CXCL10 ELISA -/41 ACR Ericzon et al (34) Bile acids ELISA -/10 Graft function CA/CDCA ratio HPLC Buis et al (35) Bile phospholipid/bile salt ratio ELISA, spectrophotometry -/111 NAS Chen et al (36) Bile salt/phospholipid ratio ELISA 90/-Bile duct injury/NAS Geuken et al (37) Bile salt/phospholipid ratio ELISA -/28 NAS ALP Spectrophotometry…”

Section: Rt-qpcrmentioning

confidence: 99%

“…At the time of donor procurement ↑ PC Identify steatotic grafts (41) ↓ Choleretic activity Identify suboptimal grafts (10) ↓ CA/CDCA ratio Identify suboptimal grafts (34) During NMP HCO − 3 >18 mmol/L, pH >7.48, glucose <16 mmol/L, bile/perfusate glucose ratio <0.67, and LDH concentration <3689 U/L Predict low histological degree of bile duct injury (2) Bile production >10 mL and pH >7.45 Predict bile duct viability (14) pH <7.85 Predict NAS (16) pH <7.4 Predict NAS (53) After transplantation ↓ Na + and ↑ bile glucose-blood glucose Predict NAS (12) ↓↓↓ Lipids Identify PNF (24) ↑ CDmiR Predict ACR (26) ↑ miR-133a, miR-148a, and miR-194 Predict ACR (27,31,46,49,50) ↑ IL2, IL6, and IL8 Predict ACR (30)(31)(32) ↑ CXCL9/10 Predict ACR (27,33) ↓ Bile salt, phospholipids, and cholesterol during the first week after LT Predict NAS (35) ↑ Bile salt/phospholipid ratio during the first week after LT Predict histologically severe bile duct injury (37) ↑ miR-517a, miR-106a, and miR-892a…”

Section: Bile Composition Goalmentioning

confidence: 99%

“…Newer techniques, such as analysis of miRNAs or proteomics, have also been described to identify biomarkers predictive of ACR. (26)(27)(28) For example, Schmuck et al showed that increased levels of certain miRNAs in bile in the first 2 postoperative weeks were predictive of ACR within 6 months after LT. (27) Verhoeven et al found that levels of hepatocyte-derived microRNAs (HDmiRs) and cholangiocyte-derived microRNAs (CDmiRs) in bile strongly correlate with cellular excretory function. (26) During episodes of rejection, HDmiRs in bile decreased and CDmiRs increased, whereas this effect was opposite in serum.…”

Section: Bile Composition After Lt: Graft Function and Cellular Rejecmentioning

confidence: 99%

See 2 more Smart Citations

Bile Composition as a Diagnostic and Prognostic Tool in Liver Transplantation

2020

View full text Add to dashboard Cite

Bile secretion and composition reflects the functional status of hepatocytes and cholangiocytes. Bile composition can have a role in the assessment of donor grafts before implantation in the recipient. In addition, changes in bile composition after liver transplantation can serve as a diagnostic and prognostic tool to predict posttransplant complications, such as primary nonfunction, acute cellular rejection, or nonanastomotic biliary strictures. With the popularization of liver machine perfusion preservation in the clinical setting, there is a revisited interest in biliary biomarkers to assess graft viability before implantation. This review discusses current literature on biliary biomarkers that could predict or assess liver graft and bile duct viability. Bile composition offers an exciting and novel perspective in the search for reliable hepatocyte and cholangiocyte viability biomarkers.

show abstract

Section: Rt-qpcrmentioning

confidence: 99%

Section: Bile Composition Goalmentioning

confidence: 99%

Section: Bile Composition After Lt: Graft Function and Cellular Rejecmentioning

confidence: 99%

See 1 more Smart Citation

Bile Composition as a Diagnostic and Prognostic Tool in Liver Transplantation

2020

View full text Add to dashboard Cite

show abstract

“…In fact, miR-122-5p is the most abundant liver-derived miRNA, constituting 70% of the total miRNA in the liver (14), and thus, a significant increase in this miRNA could be associated with hepatocyte damage, toxicity, or viral infection (15). Schmuck et al also demonstrated that the levels of miR-122-5p, miR-133a, miR-148a-3p, and miR-194 are significantly higher in the bile of liver recipients who develop AR within the first 6 months after transplantation and during the AR episode (16). Recently, Shaked et al, by using the framework of the Immune Tolerance Network Immunosuppression Withdrawal (ITN030ST) and Clinical Trials in Organ Transplantation (CTOT-03) studies, identified in plasma two miRNAs (miR-483-3p and miR-885-5p) that, when combined together in a signature, could diagnose and predict liver rejection with high accuracy [area under the curve (AUC) = 89.5%; 95% CI = 82–96%; sensitivity = 83.8%; specificity = 87.1%; positive predictive value (PPV) = 72% and negative predictive value (NPV) = 93%] (7).…”

Section: Introductionmentioning

confidence: 99%

Monitoring of miR-181a-5p and miR-155-5p Plasmatic Expression as Prognostic Biomarkers for Acute and Subclinical Rejection in de novo Adult Liver Transplant Recipients

et al. 2019

View full text Add to dashboard Cite

Background and Aims: News strategies for the accurate assessment of the state of immunosuppression (IS) in liver transplant recipients are needed to prevent rejection and minimize drug-related side effects. miRNAs can potentially be used as diagnostic or prognostic biomarkers in transplant patients. This study evaluated the capacity of a plasmatic miRNA panel (miR-155-5p, miR-122-5p, miR-181a-5p, and miR148-3p) as an early non-invasive prognostic and diagnostic biomarker for T cell-mediated acute rejection (TCMAR) and subclinical rejection (SCR) in adult liver recipients. Methods: A total of 145 liver recipients were included. All patients received a calcineurin inhibitor with or without mycophenolate mofetil and methylprednisolone. Plasmatic miRNA expression was assessed by qPCR before and at different time-points after liver transplantation. Results: Seventeen patients experienced TCMAR, and eight were diagnosed with SCR during the protocol biopsy at the 3rd month post-transplantation. Pre-transplantation, miR-155-5p expression was significantly higher in TCMAR patients and in SCR patients than in non-rejectors, and miR-181a-5p expression was also significantly higher in SCR patients than in non-rejectors. Post-transplantation, before transaminase-level modification, significantly increased miR-181a-5p, miR-155-5p, and miR-122-5p expression was observed in TCMAR and SCR patients. Binary logistic regression analyses showed, post-transplantation, that TCMAR risk was better predicted by individual expression of miR-181a-5p (LOGIT = −6.35 + 3.87 * miR-181a-5p), and SCR risk was better predicted by the combination of miR-181a-5p and miR-155-5p expression (LOGIT = −5.18 + 2.27 * miR-181a-5p+1.74 * miR-155-5p). Conclusions: Pre-transplantation plasmatic miR-155-5p expression may be useful for stratifying low-immunologic-risk patients, and post-transplantation miR-181a-5p and miR-155-5p may be candidates for inclusion in early, non-invasive prognostic biomarker panels to prevent TCMAR or SCR and better identify patient candidates for IS minimization. Large prospective randomized multicenter trials are needed to refine the cut-off values and algorithms and validate the clinical usefulness of these biomarkers.

show abstract

“…The early diagnosis of acute renal rejection is important for effective treatment with immunosuppressants and corticosteroids. Increasing evidence has demonstrated that miRNAs are differentially expressed in acute renal rejection and serve essential roles in its progression ( 34 – 36 ). Previous studies have reported that miRNAs may be used as a liquid biopsy tool, for applications including distinguishing squamous cell carcinoma in lung cancer biopsies ( 37 ), and predicting the pathological response ( 38 ) of patients with and without acute rejection ( 39 , 40 ).…”

Section: Discussionmentioning

confidence: 99%

Essential role of microRNA-650 in the regulation of B-cell CLL/lymphoma 11B gene expression following transplantation: A novel mechanism behind the acute rejection of renal allografts

et al. 2017

View full text Add to dashboard Cite

Kidney transplantation is an effective final therapeutic procedure for patients with end-stage kidney failure. Although advanced immunosuppressive therapy is administered following transplantation, certain patients still suffer from acute allograft rejection. MicroRNAs (miRs) have a potential diagnostic and therapeutic value for acute renal allograft rejection; however, their underlying mechanism of action is largely unknown. In the present study, an increased level of miR-650 was identified to be associated with the downregulation of B-cell CLL/lymphoma 11B (BCL11B) expression in acute renal allograft rejection. Furthermore, in vitro study using human renal glomerular endothelial cells (HRGECs) transfected with a miR-650 mimic revealed that key characteristics of acute renal allograft rejection were observed, including apoptosis, the release of cytokines and the chemotaxis of macrophages, while the effects were reduced in HRGECs transfected with a miR-650 inhibitor. The existence of a conserved miR-650 binding site on the 3′-untranslated region of BCL11B mRNA was predicted by computational algorithms and confirmed by a luciferase reporter assay. Knockdown of BCL11B with small interfering RNA (siRNA) significantly increased the apoptotic rate and significantly decreased the proliferation ability of HRGECs compared with the negative control group. HRGECs transfected with a combination of BCL11B siRNA and the miR-650 mimic demonstrated a significant increase in the rate of apoptosis compared with the control. These results suggest that the upregulation of miR-650 contributes to the development of acute renal allograft rejection by suppression of BCL11B, which leads to apoptosis and inflammatory responses. Thus, miR-650 and BCL11B may represent potential therapeutic targets for the prevention of acute renal allograft rejection.

show abstract

Bile: miRNA pattern and protein-based biomarkers may predict acute cellular rejection after liver transplantation

Abstract: Analysis of secretome and miRNA in bile could improve our understanding of the local inflammatory process during rejection.

Cited by 9 publications

References 41 publications

Bile Composition as a Diagnostic and Prognostic Tool in Liver Transplantation

Bile Composition as a Diagnostic and Prognostic Tool in Liver Transplantation

Monitoring of miR-181a-5p and miR-155-5p Plasmatic Expression as Prognostic Biomarkers for Acute and Subclinical Rejection in de novo Adult Liver Transplant Recipients

Essential role of microRNA-650 in the regulation of B-cell CLL/lymphoma 11B gene expression following transplantation: A novel mechanism behind the acute rejection of renal allografts

Contact Info

Product

Resources

About