Myositis‐specific autoantibodies: an important tool to support diagnosis of myositis

Abstract

The idiopathic inflammatory myopathies are characterized by muscle weakness, skin disease and internal organ involvement. Autoimmunity is known to have a role in myositis pathogenesis, and myositis‐specific autoantibodies, targeting important intracellular proteins, are regarded as key biomarkers aiding in the diagnosis of patients. In recent years, a number of novel myositis autoantibodies including anti‐TIF1, anti‐NXP2, anti‐MDA5, anti‐SAE, anti‐HMGCR and anti‐cN1A have been identified in both adult and juvenile patients. These autoantibodies correlate with distinct clinical manifestations and importantly are found in inclusion body, statin‐induced, clinically amyopathic and juvenile groups of myositis patients, previously believed to be mainly autoantibody negative. In this review, we will describe the main myositis‐specific and myositis‐associated autoantibodies and their frequencies and clinical associations across different ages and ethnic groups. We will also discuss preliminary studies investigating correlations between specific myositis autoantibody titres and clinical markers of disease course, collectively demonstrating the utility of myositis autoantibodies as both diagnostic and prognostic markers of disease.

Recent Approaches To Optimize Laboratory Assessment of Antinuclear Antibodies

“…In recent years, testing for specific ANAs has become useful in the evaluation of IIMs (12,13). While the patterns and specificities of ANAs in IIMs are quite diverse (1,3,15), identification of certain autoantibodies is useful both for diagnosing and distinguishing between subtypes of myositis and for predicting or monitoring the development of additional clinical manifestations, including organ involvement, and risks for cancers (12,13). In general, these autoantibodies are categorized as myositisspecific antibodies (MSAs) or myositis-associated antibodies (MAAs).…”

“…This is particularly important in SARDs such as SSc and IIMs (3,13,21,46,47). For example, patients with myositis have been reported to test positive for a variety of antibodies that target complex autoantigens (for example, tRNA synthetases, signal recognition particle [SRP], or Mi-2) associated with specific ANA IFA patterns (15), which currently require more specialized forms of testing, such as protein immunoprecipitation or RNA immunoprecipitation techniques, that are not readily available in clinical diagnostic laboratories.…”

“…Automation of both ends of ANA testing (front-end processing and digital reading) significantly minimizes the manual and analytical challenges of ANA IFA testing. There are a number of commercially available systems for automated reading of ANA IFA results (Table 2) based on the principles outlined above, with some variations (13,(49)(50)(51)(52)(53)(54)(55)(56)(57)(58). These systems differ from each other with respect to the use of DNA-binding counterstains (4=,6-diamidino-2-phenylindole [DAPI], propidium iodide, or none), the cell substrate used (HEp-2 versus HEp-2000, with restriction to the manufacturer's slides), throughput (samples per hour), the number of patterns that can be identified, titer prediction, front-end automation (slide processors), and other software features (49,50).…”

“…The use of HEp-2 cells, of human larynx epithelioma origin, provided increased sensitivities for detecting ANAs, probably due to their ability to divide rapidly in vitro as well as the presence of large nuclei, which allowed optimal detection of patterns associated with specific autoantibodies in SARDs (4,9,10). Although the ANA IFA method continued to be plagued by a number of analytical and diagnostic challenges, increasing recognition of the use of autoantibodies to diagnose and to further stratify SARDs, as well as efforts to harmonize the nomenclatures for testing and reporting, makes this a powerful screening tool (1,(11)(12)(13)(14)(15)(16)(17). Thus, testing for ANAs or ANA-specific autoantibodies has been incorporated in a few guidelines on diagnostic criteria.…”

Autoimmun myopati ved statinbruk

“…De har ikke anti-HMGCRantistoffer, men opptil 50 % har klassiske myosittspesifikke antistoffer (13,14).…”