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.

Barzago, C., Lum, J., Cavalcante, P., Srinivasan, K., Faggiani, E., Camera, G., et al. (2016). A novel infection- and inflammation-associated molecular signature in peripheral blood of myasthenia gravis patients. IMMUNOBIOLOGY, 221(11), 1227-1236 [10.1016/j.imbio.2016.06.012].

A novel infection- and inflammation-associated molecular signature in peripheral blood of myasthenia gravis patients

BONANNO, SILVIA;
2016

Abstract

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.
Articolo in rivista - Articolo scientifico
Inflammation; microRNAs; Myasthenia gravis; Peripheral blood mononuclear cells; Viral infection; Whole-transcriptome sequencing;
Inflammation; MicroRNAs; Myasthenia gravis; Peripheral blood mononuclear cells; Viral infection; Whole-transcriptome sequencing; Immunology; Immunology and Allergy; Hematology
English
1227
1236
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Barzago, C., Lum, J., Cavalcante, P., Srinivasan, K., Faggiani, E., Camera, G., et al. (2016). A novel infection- and inflammation-associated molecular signature in peripheral blood of myasthenia gravis patients. IMMUNOBIOLOGY, 221(11), 1227-1236 [10.1016/j.imbio.2016.06.012].
Barzago, C; Lum, J; Cavalcante, P; Srinivasan, K; Faggiani, E; Camera, G; Bonanno, S; Andreetta, F; Antozzi, C; Baggi, F; Calogero, R; Bernasconi, P; Mantegazza, R; Mori, L; Zolezzi, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/132168
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