Distinct interferon signatures stratify inflammatory and dysimmune myopathies

Muriel Rigolet (1) , Cyrielle Hou (2) , Yasmine Baba Amer , Jessie Aouizerate (3) , Baptiste Periou , Romain K. Gherardi (4) , Peggy Lafuste (5) , François Authier (6) , Yasmine Baba Amer , François Jérôme Authier

1 UPEC Médecine - Université Paris-Est Créteil Val-de-Marne - Faculté de médecine
2 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
3 Service de néphrologie [CHU Henri Mondor]
4 IMRB - Institut Mondor de Recherche Biomédicale
5 Vesalius Research Center
6 Signalisation et physiopathologie des cellules épithéliales

What is already known about this subject? ► among inflammatory/dysimmune myopathies (iDMs), dermatomyositis (DM) is the only associated with type i-interferon signature. ► Most iDMs are associated with myofiber expression of major histocompatibility complex (MHc)-class i. MHc-i is induced by interferons suggesting a possible role for type ii-interferon in iDMs other than DM. What does this study add? ► in this study, we showed that myofiber MHc-ii expression is observed in inclusion body myositis (iBM) and antisynthetase myositis (aSM), but not in DM and necrotizing autoimmune myopathy (naM). ► in accordance with this finding, we showed that iBM and aSM are specifically associated with type-ii iFnγ signature, DM only with type-i iFn signature, and naM with neither type-i nor type-ii iFn signature. How might this impact on clinical practice? ► Distinct iFn signatures allow a more distinct segregation of iDMs and therefore a more accurate diagnosis. ► Deciphering iFn signatures in iDMs will also lead to develop new therapeutic approaches targeting iFns pathways. AbstrAct Objective the role of interferons (iFn) in the pathophysiology of primary inflammatory and dysimmune myopathies (iDM) is increasingly investigated, notably because specific neutralisation approaches may constitute promising therapeutic tracks. in present work we analysed the muscular expression of specific iFnα/β and iFnγ-stimulated genes in patients with various types of iDM. Methods 39 patients with iDM with inclusion body myositis (iBM, n=9), dermatomyositis (DM, n=10), necrotising autoimmune myopathies (naM, n=10) and antisynthetase myositis (aSM, n=10), and 10 controls were included. Quantification of expression levels of iFnγ, iSg15, an iFnα/β-inducible gene and of six iFnγ-inducible genes (gBP2, Hla-DOB, Hla-DPB, ciita, Hla-DrB and Hla-DMB) was performed on muscle biopsy samples. Results DM usually associated with strong type i iFnα/β signature, iBM and aSM with prominent type ii iFnγ signature and naM with neither type i nor type ii iFn signature. immunofluorescence study in aSM and iBM showed myofibre expression of major histocompatibility class 2 (MHc-2) and ciita, confirming the induction of the iFnγ pathway. Furthermore, MHc-2-positive myofibres were observed in close proximity to cD8+ t cells which produce high levels of iFnγ. Conclusion Distinct iFn signatures allow a more distinct segregation of iDMs and myofibre MHc-2 expression is a reliable biomarker of type ii iFn signature.

Domaines: Sciences du Vivant [q-bio]; Médecine humaine et pathologie

Muriel Rigolet, Cyrielle Hou, Yasmine Baba Amer, Jessie Aouizerate, Baptiste Periou, et al.. Distinct interferon signatures stratify inflammatory and dysimmune myopathies. RMD Open : Rheumatic & Musculoskeletal Diseases, 2019, 5 (1), pp.e000811. ⟨10.1136/rmdopen-2018-000811⟩. ⟨hal-02354248⟩