Autoimmune rheumatologic diseases

Oral

Myositis From Mouse to Man: New Insight from a Unique Experimental Paradigm

Thursday, June 15
3:52 PM - 4:05 PM

Myositides are characterized by muscle weakness, leading to bedridden state and possibly death. Pathophysiological studies and therapeutic advances have been hampered by the lack of appropriate mouse models. We report the first model of spontaneous autoimmune myositis not requiring active immunization.



Disease clinical evolution in both Icos-/- and Icosl-/- NOD mice was attested by significantly decreased muscle grip strength and locomotor disability (impaired cadence and print area). Pathological analysis revealed the presence of necrotic myofibers and important inflammatory infiltrates (CD4+ T cells, macrophages). Muscle lesions were objectifiable using small animal MRI, correlated with histopathology and regressed under steroid therapy. CD4+ T cells were Th1 biased. Myositis developed in CD8- but not CD4-deficient mice. Disease was conferred to NOD.scid recipients by Icosl-/- CD4+ T cell adoptive transfer. Promoting in vivo activated CD4+ effector T cells, administration of IL-2/anti-IL2 complexes exacerbated myopathy. Serum proteomic analysis revealed five potential autoantibody targets, among two were over-expressed in diseased muscle. Searching for corresponding auto-antibodies in patients, we developed a ALBIA (Luminex™ immunoassay) using human ortholog proteins. One of them revealed positivity in a minority of individuals from a ~700 patients cohort.



These results establish the Icos-/- and Icosl-/- NOD mice as a unique paradigm of myositis, useful for pathophysiological and therapeutic research. It justifies performing MRI-guided muscle biopsy in patients. Further analyses will determine if it allowed to discover a new myositis-specific autoantibody.

Gwladys Bourdenet

Inserm U1234

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Claire Briet

Inserm U1016

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Laurent Drouot

Inserm U1234

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Fabienne Jouen

Inserm U1234

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Jérémie Martinet

Inserm U1234

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Christian Boitard

Inserm U1016

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Olivier Boyer

Inserm U1234

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Myositis From Mouse to Man: New Insight from a Unique Experimental Paradigm



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