Development and validation of a nomogram to predict allograft survival after pediatric liver transplantation.

BACKGROUND: Liver transplantation is the main treatment for cholestatic liver disease and some metabolic liver diseases in children. However, no accurate prediction model to determine the survival probability of grafts prior to surgery exists. This study aimed to develop an effective prognostic model for allograft survival after pediatric liver transplantation. METHODS: This retrospective cohort study included 2032 patients who underwent pediatric liver transplantation between January 1, 2006, and January 1, 2020. A nomogram was developed using Cox regression and validated based on bootstrap sampling. Predictive and discriminatory accuracies were determined using the concordance index and visualized using calibration curves; net benefits were calculated for model comparison. An online Shiny application was developed for easy access to the model. RESULTS: Multivariable analysis demonstrated that preoperative diagnosis, recipient age, body weight, graft type, preoperative total bilirubin, interleukin-1ß, portal venous blood flow direction, spleen thickness, and the presence of heart disease and cholangitis were independent factors for survival, all of which were selected in the nomogram. Calibration of the nomogram indicated that the 1-, 3-, and 5-year predicted survival rates agreed with the actual survival rate. The concordance indices for graft survival at 1, 3, and 5 years were 0.776, 0.757, and 0.753, respectively, which were significantly higher than those of the Pediatric End-Stage Liver Disease and Child-Pugh scoring systems. The allograft dysfunction risk of a recipient could be easily predicted using the following URL: https://aspelt.shinyapps.io/ASPELT/ / CONCLUSION: The allograft survival after pediatric liver transplantation (ASPELT) score model can effectively predict the graft survival rate after liver transplantation in children, providing a simple and convenient evaluation method for clinicians and patients.

Conventional and pulsed hybrid triboelectric nanogenerator with tunable output time and wider impedance matching range.

Sliding grating-structured triboelectric nanogenerators (SG-TENGs) can multiply transferred charge, reduce open-circuit voltage, and increase short-circuit current, which have wide application prospects in self-powered systems. However, conventional SG-TENGs have an ultrahigh internal equivalent impedance, which reduces the output voltage and energy under low load resistances (<10 MΩ). The Pulsed SG-TENGs can reduce the equivalent impedance to near zero by introducing a synchronously triggered mechanical switch (STMS), but its limited output time causes the incomplete charge transfer under high load resistances (>1 GΩ). In this paper, a conventional and pulsed hybrid SG-TENG (CPH-SG-TENG) is developed through rational designing STMS with tunable width and output time. The matching relationship among grid electrode width, contactor width of STMS, sliding speed, and load resistance has been studied, which provides a feasible solution for simultaneous realization of high output energy under small load resistances and high output voltage under high load resistances. The impedance matching range is extended from zero to at least 10 GΩ. The output performance of CPH-SG-TENG under low and high load resistances are demonstrated by passive power management circuit and arc discharge, respectively. The general strategy using tunable STMS combines the advantages of conventional and pulsed TENGs, which has broad application prospects in the fields of TENGs and self-powered systems.

Development of a predictive nomogram for switching immunosuppressive drugs in pediatric liver transplant recipients.

Background: Tacrolimus (TAC) is the preferred calcineurin inhibitor (CNI) for pediatric liver transplant recipients. However, some recipients may not achieve the desired therapeutic window concentration of TAC, leading to poor prognosis. This study aimed to develop a clinical model that can predict the effectiveness of TAC in pediatric liver transplant recipients and help clinicians quickly identify cyclosporin as an alternative. Methods: We retrospectively analyzed data from 2,032 pediatric liver transplant recipients who underwent surgery at Renji Hospital, Shanghai Jiaotong University School of Medicine between 2006 and 2019. Demographic, comorbidity and pre-operative laboratory data were collected, and a nomogram was constructed using multivariate logistic regression analysis to estimate the risk of poor therapeutic outcomes for TAC-based immunosuppression. Results: The constructed nomogram included seven parameters, namely recipient CYP3A4 genotype, pre-transplant cholangitis, GRWR, spleen long diameter, serum albumin, graft volume reduction, and donor CYP genotype. The nomogram showed good discriminative ability with an area under the receiver operating characteristic curve (AUC) of 74.5% and good calibration. Decision curve analysis indicated a high potential clinical application of the model. Conclusion: This simple clinical model effectively predicts the risk of poor therapeutic outcomes in pediatric liver transplant recipients who receive TAC-based immunosuppression. Clinicians can use the model to identify cyclosporin as an alternative quickly, potentially improving patient prognosis.

Mental health in children with living donor liver transplantation: a propensity score-matched analysis.

BACKGROUND: This study explored mental health of pediatric patients with living donor liver transplantation. METHODS: A total of 741 children who successfully underwent living donor liver transplantation from 2009 to 2019 enrolled in this study. Participants were aged between 3 and 12 years (mean age = 5.28; SD = 2.01). The Strengths and Difficulties Questionnaire was used to evaluate emotional and behavioral problems. Parents completed the 5-item World Health Organization Well-Being Index and reported their child's height, weight, sleep duration, parent-child interactions, home environment, physical activities, and time spent on screen exposure. Propensity score matching method was used to generate a control group from 20,934 healthy children. Univariate analysis and multiple logistic regression analyses were used to identify the correlational factors in children's mental health following a liver transplantation. RESULTS: Compared to healthy children, patients after liver transplantation were prone to emotional problems, hyperactivity, and peer problems. Moreover, parental mental health, physical activity, and family environment were identified as factors associated with mental health of pediatric liver transplant patients. CONCLUSION: The findings highlight the need to focus on mental health of pediatric transplant patients, increase support for parents, and strengthen positive parent-child interactions.

Power management strategy for unidirectional current pulsed triboelectric nanogenerator.

Power management circuit (PMC) can efficiently store the output energy of pulsed triboelectric nanogenerator (Pulsed-TENG). Unidirectional current Pulsed-TENG (UP-TENG) has the advantage of without using rectifier bridge. However, the energy storage efficiency is limited for large capacitors at low capacitor voltage (<10 V). To solve this problem, PMC is optimized here. Firstly, rectifier diode is used to reduce the energy loss. Energy storage efficiency of PMC using rectifier diode (D-PMC) is higher than that of conventional PMC. Then, appropriate inductor is used to further form the optimized PMC (O-PMC), which reduces the energy loss of inductor. Results show that O-PMC using 100µH inductor has the highest energy storage efficiency. The actual test energy storage efficiency of O-PMC is 30.6%, which 3.4 times higher than that of D-PMC. Finally, an external capacitor is connected to electrodes of UP-TENG to form the EUP-TENG, which improves charging speed and output voltage of O-PMC. O-PMC using EUP-TENG can stably power calculator at low motion frequencies. O-PMC can be widely used in self-powered systems.

Pediatric living-donor liver transplantation using right posterior segment grafts.

BACKGROUND: The right posterior segment (RPS) graft was introduced to overcome graft size discrepancy in living donor liver transplantation (LDLT). However, it was very rarely used in pediatric patients. Here we presented 4 pediatric LDLT cases receiving RPS graft between January 2015 and April 2020 in our center. A total of 1868 LDLT procedures were performed in this period. METHODS: Recipients included 1 boy and 3 girls with a median age of 45 months (range from 40 to 93 months). They were diagnosed with progressive familial intrahepatic cholestasis, propionic academia, ornithine transcarbamylase and biliary atresia, respectively. Four donors were all mothers with a median age of 32.5 years (31-38 years). Computer tomography angiography indicated posterior right branches branched off separately from main portal veins (type III variation). Three of these donor livers had 1 orifice of right hepatic veins (RHV). In the remaining 1 donor liver, the RHV showed 3 orifices and an outflow patch plastic was performed. Inferior right hepatic veins weren't found in four donor grafts. The median graft weight was 397.5 g (352-461 g) and the median graft-to-recipient weight ratio was 2.38% (1.44-2.80%). RESULTS: Postoperative complications occurred in neither donors nor recipients. Within the median follow-up duration of 29 months (14-64 months), four children are all alive with normal liver function. CONCLUSION: In summary, for older children weighed more than 15 kg with donors' variation of type III portal veins, the use of RPS grafts could be a feasible and favorable option.

Tim-3 adaptor protein Bat3 is a molecular checkpoint of T cell terminal differentiation and exhaustion.

T cell exhaustion has been associated with poor prognosis in persistent viral infection and cancer. Conversely, in the context of autoimmunity, T cell exhaustion has been favorably correlated with long-term clinical outcome. Understanding the development of exhaustion in autoimmune settings may provide underlying principles that can be exploited to quell autoreactive T cells. Here, we demonstrate that the adaptor molecule Bat3 acts as a molecular checkpoint of T cell exhaustion, with deficiency of Bat3 promoting a profound exhaustion phenotype, suppressing autoreactive T cell-mediated neuroinflammation. Mechanistically, Bat3 acts as a critical mTORC2 inhibitor to suppress Akt function. As a result, Bat3 deficiency leads to increased Akt activity and FoxO1 phosphorylation, indirectly promoting Prdm1 expression. Transcriptional analysis of Bat3 -/- T cells revealed up-regulation of dysfunction-associated genes, concomitant with down-regulation of genes associated with T cell effector function, suggesting that absence of Bat3 can trigger T cell dysfunction even under highly proinflammatory autoimmune conditions.

Living donor liver transplantation for pediatric patients with metabolic disease vs. deceased donation.

BACKGROUND: There are conflicting reports on the outcomes of patients with metabolic liver disease after liver transplantation. We aimed to compare the outcomes of living donor liver transplantation (LDLT) for metabolic disease vs orthotopic liver transplantation (OLT) from deceased donation. METHODS: Clinical data of 89 patients undergoing liver transplantation for the treatment of metabolic disorders were reviewed. Pre- and peri-transplant demographics, survival rate, complications and laboratory test data were collected and analyzed. RESULTS: For the 89 patients, only 2 died by the end of the last follow-up. The post-transplant EAD rate and severe complications were higher for OLT than LDLT. No significant difference was found between LDLT and OLT for the incidence of EBV and CMV infections. In terms of laboratory indexes, the recovery time of PLT, AKP and AST levels were significantly longer for OLT than LDLT. Among different types of metabolic disease, no significant difference was found in viral infection, EAD, laboratory indexes, severe complications or duration of hospital stay. CONCLUSIONS: LDLT shows a lower incidence rate of EAD and complications, while it also shows a 1-year survival rate and incidence of viral infections compared similar to that of OLT. LDLT is the better treatment option of pediatric liver transplantation for metabolic liver disease compared with OLT.

The utility of two-dimensional shear wave elastography and texture analysis for monitoring liver fibrosis in rat model.

BACKGROUND: Liver fibrosis is a common pathological change caused by a variety of etiologies. Early diagnosis and timely treatment can reverse or delay disease progression and improve the prognosis. This study aimed to assess the potential utility of two-dimensional shear wave elastography and texture analysis in dynamic monitoring of the progression of liver fibrosis in rat model. METHODS: Twenty rats were divided into control group (n = 4) and experimental groups (n = 4 per group) with carbon tetrachloride administration for 2, 3, 4, and 6 weeks. The liver stiffness measurement was performed by two-dimensional shear wave elastography, while the optimal texture analysis subsets to distinguish fibrosis stage were generated by MaZda. The results of elastography and texture analysis were validated through comparing with histopathology. RESULTS: Liver stiffness measurement was 6.09 ± 0.31 kPa in the control group and 7.10 ± 0.41 kPa, 7.80 ± 0.93 kPa, 8.64 ± 0.93 kPa, 9.91 ± 1.13 kPa in the carbon tetrachloride induced groups for 2, 3, 4, 6 weeks, respectively (P < 0.05). By texture analysis, histogram and co-occurrence matrix had the most frequency texture parameters in staging liver fibrosis. Receiver operating characteristic curve of liver elasticity showed that the sensitivity and specificity were 95.0% and 92.5% to discriminate liver fibrosis and non-fibrosis, respectively. In texture analysis, five optimal parameters were selected to classify liver fibrosis and non-fibrosis. CONCLUSIONS: Two-dimensional shear wave elastography showed potential applications for noninvasive monitoring of the progression of hepatic fibrosis, even in mild fibrosis. Texture analysis can further extract and quantify the texture features in ultrasonic image, which was a supplementary to further visual information and acquired high diagnostic accuracy for severe fibrosis.

Role of Innate Immunity in Pediatric Post-transplant Idiopathic Liver Fibrosis.

Pediatric post-transplant idiopathic liver fibrosis is an unexplained graft fibrosis that occurs in symptom-free children without acute rejection and surgical complications. Despite a lack of consensus on the subject, the development of pediatric post-transplant idiopathic liver fibrosis is believed to be the result of multiple potential factors, including ischemia-reperfusion injury, allogeneic acute and chronic rejection, viral hepatitis recurrence, opportunistic infection, and drug-induced liver damage. Among them, there is growing evidence that innate immunity may also have a unique role in this progression. This study reviews the features of pediatric post-transplant idiopathic liver fibrosis and discusses current studies illustrating the potential mechanisms of liver allograft tolerance induced by intrahepatic innate immunity, the role of components including Toll-like receptors (TLRs), interferons (IFN), dendritic cells (DC), natural killer cells (NK cells), NKT cells, neutrophils, and Kupffer cells, as well as their possibly relevant role in the development of pediatric post-transplant idiopathic liver fibrosis.

Combination of Neoadjuvant Therapy and Liver Transplantation in Pediatric Multisystem Langerhans Cell Histiocytosis With Liver Involvement.

Background: Langerhans cell histiocytosis (LCH) is characterized by misguided myeloid differentiation, whose prognosis was poor with involvement of risk organs. Remaining issues include how to improve the outcomes of patients with risk-organ involvement. Methods: A retrospective study was conducted in Renji Hospital exploring the effects of neoadjuvant therapy in combination with pediatric liver transplantation (LT) for LCH patients based on data collected between October 2006 and October 2019. Results: We presented here five cases of multisystem LCH patients underwent systemic chemotherapy to control active lesions, followed by LT to treat end-stage liver diseases. Manifestations before LT included elevated transaminase levels (n = 5, 100%), jaundice (n = 4, 80%), ascites (n = 3, 60%), and variceal hemorrhage (n = 1, 20%). Three patients underwent orthotopic liver transplantation (OLT) and two underwent living donor liver transplantation (LDLT). Until December 2019, median follow-up time was 32 months (range, 2-67 months). Liver functions significantly improved compared with pre-operative conditions. One patient had perioperative hepatic artery complications and one patient had a recurrence in the lung. EBV infection occurred in four (80%) patients and CMV infection occurred in one (20%). There was one case of drug-induced liver injury diagnosed on biopsy 13 months after LT. None underwent re-transplantation and there were no rejection or portal vein and biliary complications. Conclusion: Combination of neoadjuvant therapy and LT is an effective paradigm in treatment of multisystem LCH with severe liver dysfunction. With advances in chemotherapy regimen for multisystem LCH and LT surgery, perspectives on prognosis for LCH children are promising.

Shear wave elastography for evaluation of the urgency of liver transplantation in pediatric patients with biliary atresia.

BACKGROUND: To investigate the role of two-dimensional shear wave elastography (2D-SWE) in the preoperative evaluation of pediatric patients with biliary atresia awaiting liver transplantation. METHODS: Among a total of 152 pediatric patients enrolled in this single-institution prospective study between March 2018 and August 2019, 143 patients (age range, 4-97 months; median age, 7 months; 84 males, 59 females) who underwent successful routine ultrasound examination, SWE examination, and blood test before liver transplantation were included in the final analysis. The values of liver stiffness measured by SWE were compared with ultrasound and blood test parameters by Spearman's correlation analysis. RESULTS: The overall median liver stiffness with 2D-SWE was 29.0 ± 10.9 kPa, with a range of 9.0-53.3 kPa. The success rate of 2D-SWE measurements was 98.0% (149/152). Liver stiffness measurement (LSMs) had no significant correlation with gender, age, weight, and height of the pediatric recipients. LSMs were correlated with ultrasound parameters including portal vein (PV) maximum velocity, PV direction, hepatic artery resistance index (HARI), spleen diameter, ascites, and blood test parameters (albumin level, platelet count level, and international normalized ratio). In the pediatric recipients with hepatofugal PV flow, high HARI (HARI â‰§ 0.90), and ascites, or without Kasai operation, LSMs were significantly higher (P < .05). CONCLUSIONS: SWE is feasible and valuable for assessing liver damage in children with biliary atresia awaiting liver transplantation and might be used as selection criteria for children in need of priority access to liver transplantation.

Prevention of cytomegalovirus infection after solid organ transplantation: a Bayesian network analysis.

BACKGROUND: Cytomegalovirus infection is one of the most common complications after solid organ transplantation. There have been several classes of antiviral drugs for the prevention of cytomegalovirus infection, such as acyclovir, valacyclovir, ganciclovir and valganciclovir. METHODS: We searched relevant prospective and multi-armed studies on PubMed from Jan. 1984 up to Mar. 2018. RESULTS: Seventeen prospective studies involving 2062 patients were included in the analysis. In the case of cytomegalovirus infection, the ganciclovir group (OR = 0.24, 95% CI 0.09-0.57) and the valacyclovir group (OR = 0.20, 95% CI 0.04-0.69) provided significantly better outcomes than the control group. The ganciclovir (OR = 0.37, 95% CI 0.13-0.86) and valacyclovir groups (OR = 0.31, 95% CI 0.07-0.98) showed moderate superiority compared to the acyclovir group. As for cytomegalovirus disease, the ganciclovir, valacyclovir and valganciclovir groups showed significant advantages compared with the control group (ganciclovir group: OR = 0.17, 95% CI 0.07-0.31, valacyclovir group: OR = 0.08, 95% CI 0.01-0.33, valganciclovir group: OR = 0.14, 95% CI 0.02-0.45). Similarly, the ganciclovir group (OR = 0.38, 95% CI 0.12-0.71) and the valacyclovir group (OR = 0.17, 95% CI 0.03-0.72) showed better results than the acyclovir group. CONCLUSION: Valacyclovir showed to be the most efficient antiviral for the prevention of cytomegalovirus infection and disease. Additional studies are required to evaluate putative side effects associated with valacyclovir administration.

CXCL8high inflammatory B cells in the peripheral blood of patients with biliary atresia are involved in disease progression.

Biliary atresia (BA), the most common cause of pediatric end-stage liver disease, results from fibroinflammatory obstruction of the intrahepatic and extrahepatic bile ducts. The etiology of BA has been extensively studied, and inflammation and imbalanced immune system have been identified as the main pathogenesis of BA. B cells play roles in innate and adaptive immunity, but few studies have investigated the role of B cells in BA. This study aimed to elucidate the role of B cells in the development of BA. The percentage and numbers of total B cells (23.81 ± 11.14%，P < 0.0001, 1.22 ± 0.67 × 109 L-1 , P = 0.0014) and immature B cells (25.33 ± 14.32%, P = 0.0013, 0.19 ± 0.20 × 109 L-1 , P < 0.0001) were significantly increased in the peripheral blood of patients with BA and the number of total B cells was positively correlated with gamma-glutamyl-transpeptidase in the serum of BA. High C-X-C motif chemokine ligand 8 (CXCL8) levels were detected in the serum of patients with BA. As an important source of CXCL8, B cells from patients with BA secreted more CXCL8 into peripheral blood than those from control patients. Moreover, immature B cells can secrete more CXCL8 than mature B cells, and B cells secreted CXCL8 upon activation of the nuclear factor-κB pathway. Taken together, the results revealed that B cells have a strong ability to secrete CXCL8, which is associated with the pathogenesis of BA, and exert a proinflammatory effect on the development of BA.

Innate Immune Cells in Immune Tolerance After Liver Transplantation.

Currently, liver transplantation is the most effective treatment for end-stage liver disease. Immunosuppressive agents are required to be taken after the operations, which have significantly reduced rejection rates and improved the short-term (<1 year) survival rates. However, post-transplant complications related to the immunosuppressive therapy have led to the development of new protocols aimed at protecting renal function and preventing de novo cancer and dysmetabolic syndrome. Donor specific immune tolerance, which means the mature immune systems of recipients will not attack the grafts under the conditions without any immunosuppression therapies, is considered the optimal state after liver transplantation. There have been studies that have shown that some patients can reach this immune tolerance state after liver transplantation. The intrahepatic immune system is quite different from that in other solid organs, especially the innate immune system. It contains a variety of liver specific cells, such as liver-derived dendritic cells, Kupffer cells, liver sinusoidal endothelial cells, liver-derived natural killer (NK) cells, natural killer T (NKT) cells, and so on. Depending on their specific structures and functions, these intrahepatic innate immune cells play important roles in the development of intrahepatic immune tolerance. In this article, in order to have a deeper understanding of the tolerogenic functions of liver, we summarized the molecular mechanisms of immune tolerance induced by intrahepatic innate immune cells after liver transplantation.

Partial Hepatectomy-Induced Upregulation of miR-1907 Accelerates Liver Regeneration by Activation Autophagy.

Liver regeneration after partial hepatectomy (PH) is a highly orchestrated biological process in which synchronized hepatocyte proliferation is induced after massive liver mass loss. Hepatocyte proliferation could be regulated by multiple signals, such as miRNAs and autophagy, but underlying mechanism remains unclear. Here a functional miRNA during liver regeneration was identified and its underlying mechanism was delineated in vitro and in vivo. We found that miR-1907 was highly upregulated during liver regeneration after 2/3 PH at various timepoints. The level of miR-1907 was also increased in normal liver cell line treated with HGF at different concentrations. Functionally, miR-1907 enhanced hepatocyte proliferation in vitro and in vivo, and the liver/body weight ratio in miR-1907-overexpressed mice was significantly higher in comparison to the control mice after 2/3 PH. Forced expression of miR-1907 promoted autophagy activation of hepatocyte. Importantly, autophagy inhibition significantly attenuated miR-1907-induced hepatocyte proliferation and the liver/body weight ratio. Finally, GSK3ß, a suppressor of autophagy signaling, was identified as the direct target gene of miR-1907. Taken together, miR-1907 accelerates hepatocyte proliferation during liver regeneration by activating autophagy; thus pharmacological intervention regulating miR-1907/autophagy axis may be therapeutically beneficial in liver transplantation and liver failure by inducing liver regeneration.

Dual Effect of Hepatic Macrophages on Liver Ischemia and Reperfusion Injury during Liver Transplantation.

Ischemia-reperfusion injury (IRI) is a major complication in liver transplantation (LT) and it is closely related to the recovery of grafts' function. Researches has verified that both innate and adaptive immune system are involved in the development of IRI and Kupffer cell (KC), the resident macrophages in the liver, play a pivotal role both in triggering and sustaining the sterile inflammation. Damage-associated molecular patterns (DAMPs), released by the initial dead cell because of the ischemia insult, firstly activate the KC through pattern recognition receptors (PRRs) such as toll-like receptors. Activated KCs is the dominant players in the IRI as it can secret various pro-inflammatory cytokines to exacerbate the injury and recruit other types of immune cells from the circulation. On the other hand, KCs can also serve in a contrary way to ameliorate IRI by upregulating the anti-inflammatory factors. Moreover, new standpoint has been put forward that KCs and macrophages from the circulation may function in different way to influence the inflammation. Managements towards KCs are expected to be the effective way to improve the IRI.

Differential Expression of Long Noncoding RNAs During Cardiac Allograft Rejection.

BACKGROUND: Organ transplantation is the most effective treatment for end-stage diseases. Although transplant rejection is the major restriction in successful long-lasting graft survival, induction of sustainable immune tolerance against transplant is one of the major goals in transplantation to enable long-term graft survival. Although various mechanisms have been suggested that induce immune tolerance during transplantation, the roles of long noncoding RNAs (lncRNAs), which modulate gene expression and regulate innate and adaptive immune responses, are not clearly understood in transplantation. Here, we described the role of 2 essential lncRNAs, lncRNA-A930015D03Rik and mouselincRNA1055, in regulating T helper 1 (Th1) response in graft rejection. METHODS: To understand the gene expression and lncRNA profile during transplantation, we performed microarray to profile lncRNA and messenger (m)RNA of the heart graft and graft-infiltrating lymphocytes (GILs) in allogeneic and syngeneic mouse heart transplantation model. We screened the differentially expressed lncRNAs and mRNAs, and generated the network of lncRNA-mRNA coexpression and computationally predicted their association in transplantation. We further validated the selected T cell related lncRNAs by qPCR, which we identified in gene set enrichment analysis. The functional validation of these lncRNAs in the regulation of Th1 response in transplantation was performed by short hairpin RNA-mediated inhibition. RESULTS: We established a profile of lncRNA and mRNA, which are differentially expressed during transplant rejection in mouse model of heart transplant. Consistent with the microarray results, we have confirmed and validated the expression of 7 lncRNA by qPCR. The lncRNA-A930015D03Rik and mouselincRNA1055 were highly expressed in allogeneic heart graft and GILs. We further identified that expression of IL-12Rß1 is strongly correlated with lncRNA-A930015D03Rik and mouselincRNA1055 in GILs. Further analysis revealed the association of lncRNA-A930015D03Rik and mouselincRNA1055 with Th1 cells in graft rejection. The functions of lncRNA-A930015D03Rik and mouselincRNA1055 were validated in differentiation of Th1 cells by knocking down their expression. Inhibition of lncRNA-A930015D03Rik and mouselincRNA1055 substantially suppressed the expression of IL-12Rß1 and IFN-γ induction in Th1 cells. CONCLUSIONS: Our results provide a detailed profile of lncRNAs that may regulate immune response and graft outcomes. Our data not only suggest the involvement of lncRNA-A930015D03Rik and mouselincRNA1055 in the regulation of Th1 cells response during graft rejection but also identify them as novel biomarkers for subclinical graft rejection.