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

Claudia Barzago, Josephine Lum, Paola Cavalcante, Kandhadayar Gopalan Srinivasan, Elisa Faggiani, Giorgia Camera, Silvia Bonanno, Francesca Andreetta, Carlo Antozzi, Fulvio Baggi, Raffaele Adolfo Calogero, Pia Bernasconi, Renato Mantegazza, Lucia Mori, Francesca Zolezzi

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalImmunobiology
DOIs
Publication statusPublished - 2016

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Keywords

  • Inflammation
  • MicroRNAs
  • Myasthenia gravis
  • Peripheral blood mononuclear cells
  • Viral infection
  • Whole-transcriptome sequencing

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology

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