Renal involvement is one of the most severe manifestations of systemic lupus erythematosus (SLE). Renal biopsy is the gold standard when it comes to knowing whether a patient has lupus nephritis, and the degree of renal disease present. However, the biopsy has various complications, bleeding being the most common. Therefore, the development of alternative, non-invasive diagnostic tests for kidney disease in patients with SLE is a priority. Micro RNAs (miRNAs) are differentially expressed in various tissues, and changes in their expression have been associated with several pathological processes. The aim of this study was to identify changes in the abundance of miRNAs in plasma samples from patients with lupus nephritis that could potentially allow the diagnosis of renal damage in SLE patients. This is an observational case-control cross-sectional study, in which we characterized the differential abundance profiles of miRNAs among patients with different degrees of lupus compared with SLE patients without renal involvement and healthy control individuals. We found 89 miRNAs with changes in their abundance between lupus nephritis patients and healthy controls, and 17 miRNAs that showed significant variations between SLE patients with or without renal involvement. Validation for qPCR of a group of miRNAs on additional samples from lupus patients with or without nephritis, and from healthy individuals, showed that five miRNAs presented an average detection sensitivity of 97%, a specificity of 70.3%, a positive predictive value of 82.5%, a negative predictive value of 96% and a diagnosis efficiency of 87.9%. These results strongly suggest that miR-221-5p, miR-380-3p, miR-556-5p, miR-758-3p and miR-3074-3p are potential diagnostic biomarkers of lupus nephritis in patients with SLE. The observed differential pattern of miRNA abundance may have functional implications in the pathophysiology of SLE renal damage.
Background: The human dopamine transporter is the main regulator of dopamine tone and an intricate network exists to regulate the expression, conformation, and kinetics of the hDAT. hDAT dysfunction is directly related to Parkinson's disease. The objective of this work is to evaluate the differential gene expression in the interactome of the Dopamine transporter in the context of Parkinson's disease. Methods:To do this, we evaluated hDAT interaction data in string-db, mint.bio, IntAct, reactome, hprd and BioGRID, subsequently, data was obtained from the differential gene expression of mRNA and miRNAs for this hDAT interactome in the context of PD. Results: The analysis of the differential expression changes of genes of the hDAT interactome in tissues of patients with PD compared with tissues of individuals without PD, allowed to identify an expression pattern of 32 components of the hDAT interactome, of which 31 presented a negative change proportion in PD. Conclusions: We found a total of 90 miRNAs that could regulate the expression of 27 components of the hDAT interactome, at the same time, 39 components of the hDAT interactome may participate in 40 metabolic pathways. Together, these findings show a systematic effect on the hDAT-mediated dopamine internalization process in patients with Parkinson's, which would contribute to a greater susceptibility to neuronal oxidative stress in PD patients.
Background and aims Prolactin has been found to be associated with immune regulation in SLE. The aim of this study is to determine the correlation between high prolactin level in comparison with IL -6 with lupus nephritis disease activity in UKMMC. Methods In this cross-sectional study, the analysis was conducted in SLE patients who attended Nephrology clinic in UKMMC from August 2015 till February 2016 Results Out of 43 patients with lupus nephritis, 27.9% of the patients had raised serum prolactin. The median of serum prolactin level at 0 min was 19.91 ng/ml (IQR: 15.95-22.65 ) for active lupus nephritis that was significantly higher as compared to the median of serum prolactin level 14.34 ng/ml (IQR: 11.09-18.70 ) for patients in remission (p=0.014). The serum prolactin level was positively correlated to SLEDAI (rho s : 0.449, p=0.003 ) and UPCI level in lupus nephritis patients (rho s : 0.241, p=0.032). Assessment of serum IL-6 levels found that the active lupus nephritis patients were having a higher median level of 65.91 pg/ml (21.96-146.14) compared to in remission level of 15.84 pg/ml (IQR: 8.38-92.84), (p=0.039). ROC curve analysis of serum prolactin 0 min and serum prolactin 30 min and IL-6 level for prediction of SLE diseases activity provide the cutoff value of serum prolactin 0 min was 14.63 ng/ml with sensitivity 91.7% and specificity 58.1% and AUC of 0.74 (p=0.015). Conclusions Baseline fasting serum prolactin level was found to be a sensitive biomarker for evaluation of lupus nephritis disease activity. Background and aims Plasmacytoid dendritic cells (pDC) are potent producers of IFNa, we investigated what additional soluble factors are produced by pDCs and the effect of pDC depletion with JNJ-56022473 (JNJ-473), a novel antibody against CD123. We then investigated which of these factors are elevated in SLE patient sera to determine potential biomarkers. Methods pDCs were isolated from healthy donor (HD) PBMC (n=6) which were stimulated with CpGc (TLR9) and imiquimod (TLR7) then analysed by RNAseq. PBMC from SLE and HD were also treated with isotype or JNJ-473 before stimulation with CpGc for 24 hour. Culture supernatant, SLE (n=33) and HD sera (n=34) was analysed by bead-based multiplex assay (Myriad U.S.A).Results TLR9 and TLR7-agonism induced the regulation of thousands of genes, many of which were different IFNa-subtypes. Transcripts of many other secreted proteins such as MCP-2/CCL8, IP-10/CXCL10, ITAC/CXCL11 and MIP-3b/ CCL19 were also upregulated. Proteins of these were also found to be significantly increased in SLE sera compared to HD.Depleting pDCs with JNJ-473 in SLE and HD PBMC cultures reduced production of many CpGc-induced proteins including IFNa, MCP-2/CCL8, IP-10/CXCL10, ITAC/CXCL11 and MIP-3b/CCL19. RNAseq of SLE PBMC treated with JNJ-473 before CpGc stimulation, confirmed significantly decreased expression of MCP-2/CCL8, IP-10/CXCL10 and ITAC/CXCL11. Conclusions We found that pDC depletion with JNJ-473 was able to prevent TLR9-induced production of IFNa and various other solub...
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