Autoantibodies in idiopathic inflammatory myopathies: Clinical associations and laboratory evaluation by mono- and multispecific immunoassays

• Published in: Autoimmunity reviews Vol. 18; no. 3; pp. 293 - 305
• Main Authors: Damoiseaux, Jan, Vulsteke, Jean-Baptiste, Tseng, Chih-Wei, Platteel, Anouk C.M., Piette, Yves, Shovman, Ora, Bonroy, Carolien, Hamann, Dörte, De Langhe, Ellen, Musset, Lucille, Chen, Yi-Hsing, Shoenfeld, Yehuda, Allenbach, Yves, Bossuyt, Xavier
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2019; Elsevier
• Subjects: Autoantibodies; Humans; Immunoassay; Life Sciences; Myositis; Verification; Myositis; Verification; Autoantibodies
• ISSN: 1568-9972; 1568-9972; 1873-0183
• DOI: 10.1016/j.autrev.2018.10.004

Idiopathic inflammatory myopathies (IIM) are a group of diseases characterized by immune-mediated muscular lesions that may be associated with extra-muscular manifestations involving skin, lungs, heart or joints. Four main groups of IIM can be distinguished: dermatomyositis (DM), overlap myositis including mainly anti-synthetase syndrome (ASS), immune mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Myositis-specific autoantibodies (MSA) are increasingly recognized as valuable tools for diagnosis, classification and prognosis of IIM. For example, ASS is associated with anti-aminoacyl tRNA synthetase antibodies (anti-Jo-1, PL-7, PL-12, …), IMNM with anti-SRP and anti-HMGCR; IBM with anti-cytosolic 5’nucleotidase 1A (cN1A), and DM with anti-Mi-2, anti-MDA-5, anti-TIF-1γ, anti-NXP-2 and anti-SAE. Moreover, anti-MDA-5 is associated with amyopathic myositis and interstitial lung disease and anti-TIF-1γ and anti-NXP-2 with juvenile DM as well as malignancy in patients >40 years. Most MSA have initially been discovered by immunoprecipitation. In routine laboratories, however, MSA are screened for by indirect immunofluorescence and identified by (automated) monospecific immunoassays or by multispecific immunoassays (mainly line/dot immunoassays). Validation of these (multispecific) assays is a challenge as the antibodies are rare and the assays diverse. In this review, we give an overview of the (clinical) performance characteristics of monospecific assays as well as of multispecific assays for detection of MSA. Although most assays are clinically useful, there are differences between techniques and between manufacturers. We discuss that efforts are needed to harmonize and standardize detection of MSA. •Autoantibodies are recognized as important biomarkers for the distinct entities of idiopathic inflammatory myopathies.•The HEp-2 indirect immunofluorescence assay is inadequate as screening assay for myositis-specific autoantibodies.•Incorporation of immunoassays for myositis-specific antibodies in clinical practice requires appropriate clinical evaluation.