Background/Purpose:

Myositis specific antibodies (MSA) represent important diagnostic tools and also help stratify idiopathic inflammatory myositis (IIM) patients with particular clinical features, treatment responses, and disease outcomes. Standardization of MSA is of high importance because these antibodies also have the potential to be used in classification criteria. Many laboratories rely on immunoprecipitation (IP) for the detection of MSA but this approach is compromised by logistic, standardization, and regulatory challenges. Therefore, reliable alternatives to IP are mandatory. The objective of this study was to compare the results obtained from different assays for the detection of MSA.

Methods:

The study included 82 patients (68 females/14 males), most of whom had dermatomyositis (DM, n=57), followed by polymyositis (PM, n=16) and juvenile DM (n=9). All samples were tested using a novel particle-based multi-analyte technology (PMAT, Inova Diagnostics, research use only; Mi-2b, OJ, TIF1y, PL-12, SAE, EJ, MDA5, HMGCR, PL-7, SRP, NXP2) in parallel with a line immunoassay (LIA: Euroimmun, not FDA approved; OJ, EJ, PL-12, PL-7, SRP, Jo-1, Ro52, PM-75, PM-100, KU, SAE1, NXP2, MDA5, TIF1y, Mi-2b, Mi-2a). Principle component analysis (PCA) was carried out to analyze the relationship between the individual markers.

Results:

In our cohort of Mexico, Central, and South American myositis patients, anti-Mi-2 antibodies were the most common autoantibody detected with an overall prevalence of 28%. The prevalence of the individual MSA antibodies in the sera of IIM clinical subsets is detailed in Table 1. PCA analyses (based on PMAT results) displayed clusters of autoantibodies which are consistent with previously reported IIM clinical associations (see Figure 1). Close proximity was observed for the antibodies to synthetases (PL-7, PL-12, EJ, OJ), for HMGCR and SRP, as well as for NXP2 and TIF1y.

Figure 1:  Principle component analysis (PCA) of the different autoantibodies in myositis. DM=Dermatomyositis; CADM=clinically amyopathic DM; IMNM=immune mediated necrotizing myopathies; PM=polymyositis; ASS=anti-synthetase syndrome

Conclusion:

The novel PMAT used to detect a spectrum of MSA in IIM represents a potential alternative to IP and other diagnostic assays. Our data was consistent with previously published associations of MSA with IIM clinical phenotypes and provides further evidence that autoantibodies are useful biomarkers for accurate diagnosis, patient stratification, as well as future classification criteria.