Nuclear actin aggregation is a hallmark of anti-synthetase syndrome-induced dysimmune myopathy

Affiliations

¹ From the Departments of Neuropathology (W.S., C.P., D.P., F.L.H., H.H.G.) and Rheumatology (U.S.), Charité-Universitätsmedizin Berlin, Germany; the Département de Médecine Interne et Immunologie Clinique (Y.A., O.B.), Centre de Référence Maladies Neuro-Musculaires Paris Est, Assistance Public-Hôpitaux de Paris Université Pierre et Marie Curie, Hôpital Pitié-Salpêtrière, Paris, France; the Section of Neuropathology, Department of Anatomical Pathology (R.J.), Path West Laboratory Medicine, Royal Perth Hospital, Perth; School of Pathology and Laboratory Medicine (R.J.), University of Western Australia, Nedlands, Australia; the Institute of Neuropathology (K.N., K.G.C., J.W.) and the Department of Neurology (K.G.C.), RWTH Aachen, Germany; the Department of Pathology and Neuropathology (E.A.), AMC University, Amsterdam, the Netherlands; the Department of Neuropathology (V.K., E.R.), University of Zürich, Switzerland; and the Department of Neuropathology (H.H.G.), University Medicine, Johannes Gutenberg University, Mainz, Germany. werner.stenzel@charite.de.
² From the Departments of Neuropathology (W.S., C.P., D.P., F.L.H., H.H.G.) and Rheumatology (U.S.), Charité-Universitätsmedizin Berlin, Germany; the Département de Médecine Interne et Immunologie Clinique (Y.A., O.B.), Centre de Référence Maladies Neuro-Musculaires Paris Est, Assistance Public-Hôpitaux de Paris Université Pierre et Marie Curie, Hôpital Pitié-Salpêtrière, Paris, France; the Section of Neuropathology, Department of Anatomical Pathology (R.J.), Path West Laboratory Medicine, Royal Perth Hospital, Perth; School of Pathology and Laboratory Medicine (R.J.), University of Western Australia, Nedlands, Australia; the Institute of Neuropathology (K.N., K.G.C., J.W.) and the Department of Neurology (K.G.C.), RWTH Aachen, Germany; the Department of Pathology and Neuropathology (E.A.), AMC University, Amsterdam, the Netherlands; the Department of Neuropathology (V.K., E.R.), University of Zürich, Switzerland; and the Department of Neuropathology (H.H.G.), University Medicine, Johannes Gutenberg University, Mainz, Germany.

PMID: 25746564
DOI: 10.1212/WNL.0000000000001422

Free article

Nuclear actin aggregation is a hallmark of anti-synthetase syndrome-induced dysimmune myopathy

Werner Stenzel et al. Neurology. 2015.

Free article

. 2015 Mar 31;84(13):1346-54.

doi: 10.1212/WNL.0000000000001422. Epub 2015 Mar 6.

Authors

Affiliations

¹ From the Departments of Neuropathology (W.S., C.P., D.P., F.L.H., H.H.G.) and Rheumatology (U.S.), Charité-Universitätsmedizin Berlin, Germany; the Département de Médecine Interne et Immunologie Clinique (Y.A., O.B.), Centre de Référence Maladies Neuro-Musculaires Paris Est, Assistance Public-Hôpitaux de Paris Université Pierre et Marie Curie, Hôpital Pitié-Salpêtrière, Paris, France; the Section of Neuropathology, Department of Anatomical Pathology (R.J.), Path West Laboratory Medicine, Royal Perth Hospital, Perth; School of Pathology and Laboratory Medicine (R.J.), University of Western Australia, Nedlands, Australia; the Institute of Neuropathology (K.N., K.G.C., J.W.) and the Department of Neurology (K.G.C.), RWTH Aachen, Germany; the Department of Pathology and Neuropathology (E.A.), AMC University, Amsterdam, the Netherlands; the Department of Neuropathology (V.K., E.R.), University of Zürich, Switzerland; and the Department of Neuropathology (H.H.G.), University Medicine, Johannes Gutenberg University, Mainz, Germany. werner.stenzel@charite.de.
² From the Departments of Neuropathology (W.S., C.P., D.P., F.L.H., H.H.G.) and Rheumatology (U.S.), Charité-Universitätsmedizin Berlin, Germany; the Département de Médecine Interne et Immunologie Clinique (Y.A., O.B.), Centre de Référence Maladies Neuro-Musculaires Paris Est, Assistance Public-Hôpitaux de Paris Université Pierre et Marie Curie, Hôpital Pitié-Salpêtrière, Paris, France; the Section of Neuropathology, Department of Anatomical Pathology (R.J.), Path West Laboratory Medicine, Royal Perth Hospital, Perth; School of Pathology and Laboratory Medicine (R.J.), University of Western Australia, Nedlands, Australia; the Institute of Neuropathology (K.N., K.G.C., J.W.) and the Department of Neurology (K.G.C.), RWTH Aachen, Germany; the Department of Pathology and Neuropathology (E.A.), AMC University, Amsterdam, the Netherlands; the Department of Neuropathology (V.K., E.R.), University of Zürich, Switzerland; and the Department of Neuropathology (H.H.G.), University Medicine, Johannes Gutenberg University, Mainz, Germany.

PMID: 25746564
DOI: 10.1212/WNL.0000000000001422

Abstract

Objective: To analyze antisynthetase syndrome-associated myositis by modern myopathologic methods and to define its place in the spectrum of idiopathic inflammatory myopathies (IIMs).

Methods: Skeletal muscle biopsies from antisynthetase syndrome-associated myositis and other IIMs from different institutions worldwide were analyzed by histopathology, quantitative PCR, and electron microscopy.

Results: Myonuclear actin filament inclusions were identified as a unique morphologic hallmark of antisynthetase syndrome-associated myositis. Nuclear actin inclusions were never found in dermatomyositis, polymyositis, sporadic inclusion body myositis, autoimmune necrotizing myopathy associated with signal recognition particle or 3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies, or nonspecific myositis associated with other systemic diseases, harboring myositis-associated autoantibodies, and presenting myofiber necrosis. We show that molecules involved in actin filament formation and actin shuttling mechanisms are altered in antisynthetase syndrome, and may thus be involved in pathologic myonuclear actin aggregation. In addition, we have identified a typical topographic distribution of necrotic myofibers predominantly located at the periphery of muscle fascicles accompanied by inflammation and destruction of the perimysial connective tissue.

Conclusion: Antisynthetase syndrome-associated myositis is characterized by distinctive myonuclear actin filament inclusions, including rod formations and a typical necrotizing perimysial myositis. This supports the hypothesis that antisynthetase syndrome-associated myositis is unique and should not be grouped among dermatomyositis, polymyositis, sporadic inclusion body myositis, necrotizing autoimmune myositis, or nonspecific myositis.

Classification of evidence: This study provides Class II evidence that for patients with IIMs, the presence of myonuclear actin filament inclusions accurately identifies patients with antisynthetase syndrome-associated myositis (sensitivity 81%, specificity 100%).

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Comment in

Reply: Perifascicular necrosis in anti-synthetase syndrome beyond anti-Jo-1.
Allenbach Y, Hervier B, Stenzel W, Benveniste O. Allenbach Y, et al. Brain. 2016 Sep;139(Pt 9):e51. doi: 10.1093/brain/aww126. Epub 2016 Jun 5. Brain. 2016. PMID: 27267377 No abstract available.
Perifascicular necrosis in anti-synthetase syndrome beyond anti-Jo-1.
Uruha A, Suzuki S, Suzuki N, Nishino I. Uruha A, et al. Brain. 2016 Sep;139(Pt 9):e50. doi: 10.1093/brain/aww125. Epub 2016 Jun 5. Brain. 2016. PMID: 27267378 No abstract available.

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Nuclear actin aggregation is a hallmark of anti-synthetase syndrome-induced dysimmune myopathy

Affiliations

Nuclear actin aggregation is a hallmark of anti-synthetase syndrome-induced dysimmune myopathy

Authors

Affiliations

Abstract

Comment in

MeSH terms

Substances

Supplementary concepts

LinkOut - more resources

Full Text Sources

Medical

Research Materials