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.G., 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.
|Citazione:||Barzago C., Lum J., Cavalcante P., Srinivasan K.G., 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.|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||Si|
|Titolo:||A novel infection- and inflammation-associated molecular signature in peripheral blood of myasthenia gravis patients|
|Autori:||Barzago C.; Lum J.; Cavalcante P.; Srinivasan K.G.; Faggiani E.; Camera G.; Bonanno S.; Andreetta F.; Antozzi C.; Baggi F.; Calogero R.A.; Bernasconi P.; Mantegazza R.; Mori L.; Zolezzi F.|
|Data di pubblicazione:||2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.imbio.2016.06.012|
|Appare nelle tipologie:||01 - Articolo su rivista|