Gene expression in multiple sclerosis during pregnancy based on integrated bioinformatics analysis.

BACKGROUND: The modulation of the activity disease in patients with Multiple Sclerosis (MS) that occurs during pregnancy is a helpful model which could provide insight into central disease mechanisms and facilitate treatment. Therefore, the aim of the study was to identify differentially expressed genes in-silico to perform biological function pathway enrichment analysis and protein-protein interaction from pregnant women with MS. METHODS: Transcriptome data were obtained from the Gene Expression Omnibus (GEO) database. We selected the microarray dataset GSE17449. The gene expression dataset contains the data of mononuclear cells from four different groups sought, including seven healthy women (H), four healthy pregnant women (HP), eight women with multiple sclerosis (WMS), and nine women nine months pregnant with multiple sclerosis (PMS). The GSEA software was employed for enrichment analysis, and the REACTOME database was used for biological pathways. The protein-protein interaction (PPI) network was plotted with STRING. The databases used to identify the connection of DEGs with different signaling pathways were KEGG and WIKIPATHWAYS. RESULTS: We identified 42 differentially expressed genes in pregnant women with MS. The significant pathways included IL-10 signaling pathway, ErbB2 activates, the hemoglobin complex (HBD, HBB, HBA1, AHSP, and HBA2), IL-17 signaling pathway (LCN2 and MMP9), antigen processing and presentation, and Th17 cell differentiation (HLA-DQA1), Rap1 signaling pathway (ID1), NOD-Like receptor signaling pathway (CAMP and DEFA4), PD-L1 Signaling, Interferon gamma signaling (MMP9 and ARG1), Neutrophil degranulation (CAMP, DEFA4, ELANE, CEACAM8, S100P, CHI3L1, AZU1, OLFM4, CRISP3, LTF, ARG1, PGLYRP1, and TCN1). In the WIKIPATHWAYS set, significance was found Vitamin B12 metabolism (TCN1, HBB, and HBA2), and IL-18 signaling pathway (S100P). CONCLUSION: This study can be used to understand several essential target genes and pathways identified in the present study, which may serve as feasible targets for MS therapies.

Genetic Variant HLA-DRB1*0403 and Therapeutic Response to Disease-Modifying Therapies in Multiple Sclerosis: A Case-Control Study.

Multiple sclerosis (MS) is a chronic and demyelinating disease with an autoimmune origin, which leads to neurodegeneration and progressive disability. Approximately 30 to 50% of patients do not respond optimally to disease-modifying therapies (DMTs), and therapeutic response may be influenced by genetic factors such as genetic variants. Therefore, our study aimed to investigate the association of the HLA-DRB1*0403 genetic variant and therapeutic response to DMTs in MS. We included 105 patients with MS diagnosis. No evidence of disease activity based on the absence of clinical relapse, disability progression or radiological activity (NEDA-3) was used to classify the therapeutic response. Patients were classified as follows: (a) controls: patients who achieved NEDA-3; (b) cases: patients who did not achieve NEDA-3. DNA was extracted from peripheral blood leukocytes. HLA-DRB1*0403 genetic variant was analyzed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. NEDA-3 was achieved in 86.7% of MS patients treated with DMTs. Genotype frequencies were GG 50.5%, GA 34.3%, and AA 15.2%. No differences were observed in the genetic variant AA between patients who achieved NEDA-3 versus patients who did not achieve NEDA-3 (48.7% vs. 43.1%, p = 0.6). We concluded that in Mexican patients with MS, HLA-DRB1*0403 was not associated with the therapeutic response to DMTs.

Genetic Basis of Inflammatory Demyelinating Diseases of the Central Nervous System: Multiple Sclerosis and Neuromyelitis Optica Spectrum.

Demyelinating diseases alter myelin or the coating surrounding most nerve fibers in the central and peripheral nervous systems. The grouping of human central nervous system demyelinating disorders today includes multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) as distinct disease categories. Each disease is caused by a complex combination of genetic and environmental variables, many involving an autoimmune response. Even though these conditions are fundamentally similar, research into genetic factors, their unique clinical manifestations, and lesion pathology has helped with differential diagnosis and disease pathogenesis knowledge. This review aims to synthesize the genetic approaches that explain the differential susceptibility between these diseases, explore the overlapping clinical features, and pathological findings, discuss existing and emerging hypotheses on the etiology of demyelination, and assess recent pathogenicity studies and their implications for human demyelination. This review presents critical information from previous studies on the disease, which asks several questions to understand the gaps in research in this field.

Effect of Rituximab Compared with Natalizumab and Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis: A Cohort Study.

The objective of this study was to evaluate the clinical files of patients with RRMS who started rituximab (RTX) compared with a second-line treatment (natalizumab (NTZ) or fingolimod (FTY)). This was a historical cohort study. We compared the effect according to the Expanded Disability Status Scale (EDSS) and the number of relapses in RRMS patients receiving these treatments after a mean period of 12 months. We found a statistically significant difference (p < 0.001) when comparing the EDSS scores and the annual relapse rates of patients receiving RTX with those receiving NTZ or FTY. This study is essential for our clinical practice, since patients with limited treatment options represent a challenge with regard to the management of their medical care. However, clinical trials and prospective studies with long follow-up periods are necessary to provide sufficient evidence on the efficacy of RTX and thus include this treatment in the therapeutic profile of patients with MS.

MicroRNA-296-5p is differentially expressed in individuals with and without HIV-1 infection.

MicroRNAs are considered as potential biomarkers, agents, or therapeutic targets; few studies have addressed the expression of miRNAs in treatment-naïve patients infected with HIV-1. The aim of this study was to assess plasma relative circulating miRNA expression profiles in treatment-naïve Mexican patients with HIV/AIDS and healthy individuals using a commercial array. A low CD4+ T cell count and high viral load were found in all patients. Decreased relative miRNA-296-5p expression was observed in patients; moreover, this was the only miRNA that showed differences between the two groups. Thus, we measured the absolute expression of miR-296-5p by qPCR, confirming the result with statistically significant differences (P < 0.05). There is evidence that miR-296-5p regulates the expression of the PIN1 gene, which encodes the peptidylprolyl Cis/Trans isomerase NIMA-Interacting-1, that is involved in different stages of the biological cycle of HIV-1, this relationship is corroborated by bioinformatics analysis and ELISA assay was used to measure plasma levels of PIN1. The decreased expression of miR-296-5p found in naïve patients with HIV infection suggests a regulatory activity of this miRNA on virus replication, making it a potential therapeutic agent against HIV. Finally, miR-296-5p could be inhibiting the virus transcription by regulating genes different than PIN1.

Plasma microRNA expression levels in HIV-1-positive patients receiving antiretroviral therapy.

MicroRNAs (miRNAs/miRs) may serve as therapeutic agents or targets in diseases in which the expression of proteins plays an important role. The aim of the present study was to compare the expression levels of specific miRNAs, as well as their correlation with markers of response to antiretroviral (ARV) therapy, in patients with human immunodeficiency virus type 1 (HIV-1) infection with and without resistance to highly active antiretroviral therapy (HAART). METHODS: miRNA assays were performed on plasma samples obtained from 20 HIV-1-positive patients. A total of ten patients were divided into two groups: HAART-responsive and HAART-resistant (n=5 per group). Commercial arrays were subsequently used to identify 84 miRNAs. A total of three differentially expressed miRNAs were selected and analyzed by quantitative PCR (qPCR). Five other patients were subsequently added to each group for a new relative expression analysis. The absolute expression level of the two miRNAs was obtained and compared using the Student's t test. Receiver operating characteristic (ROC) curves were used to identify patients with antiretroviral therapy (ART) resistance. RESULTS: The array analysis revealed that miR-15b-5p, miR-16-5p, miR-20a-5p, miR-26a-5p, miR-126-3p and miR-150-5p were down-regulated in patients with HAART-resistance comparing with HAART-responsive. The expression levels of miR-16-5p, miR-26a-5p and miR-150-5p were confirmed using qPCR. The area under the ROC curve was 1.0 for the three miRNAs. CONCLUSIONS: The lower expression levels of miR-16-5p and miR-26a-5p in patients with HAART-resistance suggested that these may serve as potential biomarkers for the identification of HAART-responsive patients.