Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myasthenia gravis (MG) is an antibody-mediated autoimmune disease characterized by exertional weakness. There is no biomarker to reflect disease activity and guide treatment decision. Here, we reported a pilot blood transcriptome study using RNA sequencing (RNA-seq) that identified differences of 5 samples in active status and 5 in remission from 8 different patients and 2 patients provided samples for both active and remission phase. We found a total of 28 differentially expressed genes (DEGs) possibly related to disease activity (23 up-regulated and 5 down-regulated). The DEGs were enriched for the cell motion and cell migration processes in which included were ICAM1, CCL3, S100P and GAB2. The apoptosis and cell death pathway was also significantly enriched, which includes NFKBIA, ZC3H12A, TNFAIP3, and PPP1R15A. Our result suggests that transcript abundance profiles of the genes involved in cell trafficking and apoptosis may be a molecular signature of the disease activity in MG patients.
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PMID:Blood Transcriptome Profiling in Myasthenia Gravis Patients to Assess Disease Activity: A Pilot RNA-seq Study. 2692 32

Myasthenia gravis (MG) is a T-cell dependent autoimmune disorder of the neuromuscular junction, characterised by muscle weakness and fatigability. Autoimmunity is thought to initiate in the thymus of acetylcholine receptor (AChR)-positive MG patients; however, the molecular mechanisms linking intra-thymic MG pathogenesis with autoreactivity via the circulation to the muscle target organ are poorly understood. Using whole-transcriptome sequencing, we compared the transcriptional profile of peripheral blood mononuclear cells from AChR-early onset MG (AChR-EOMG) patients with healthy controls: 178 coding transcripts and 229 long non-coding RNAs, including 11 pre-miRNAs, were differentially expressed. Among the 178 coding transcripts, 128 were annotated of which 17% were associated with the 'infectious disease' functional category and 46% with 'inflammatory disease' and 'inflammatory response-associated' categories. Validation of selected transcripts by qPCR indicated that of the infectious disease-related transcripts, ETF1, NFKB2, PLK3, and PPP1R15A were upregulated, whereas CLC and IL4 were downregulated in AChR-EOMG patients; in the 'inflammatory' categories, ABCA1, FUS, and RELB were upregulated, suggesting a contribution of these molecules to immunological dysfunctions in MG. Data selection and validation were also based on predicted microRNA-mRNA interactions. We found that miR-612, miR-3654, and miR-3651 were increased, whereas miR-612-putative AKAp12 and HRH4 targets and the miR-3651-putative CRISP3 target were downregulated in AChR-EOMG, also suggesting altered immunoregulation. Our findings reveal a novel peripheral molecular signature in AChR-EOMG, reflecting a critical involvement of inflammatory- and infectious disease-related immune responses in disease pathogenesis.
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PMID:A novel infection- and inflammation-associated molecular signature in peripheral blood of myasthenia gravis patients. 2738 91