Abstract

(1) Background: Myositis specific antibodies (MSA) represent important diagnostic and stratification tools in idiopathic inflammatory myositis (IIM) patients. Here we aimed to evaluate the clinical performance of MSA profiled by a novel particle based multi-analyte technology (PMAT) in IIM and subsets thereof. (2) Methods: 264 IIM patients and 200 controls were tested for MSA using PMAT (Inova Diagnostics, research use only). Diagnostic performance was analyzed and composite scores were generated. (3) Results: The sensitivity/specificity of the individual MSA were: 19.7%/100% (Jo-1), 7.2%/100.0% (Mi-2), 3.0%/99.0% (NXP2), 3.8%/100.0% (SAE), 2.7%/100.0% (PL-7), 1.9%/99.5 (PL-12), 1.1%/100.0% (EJ), 15.5%/99.5% (TIF1γ), 8.3%/98.5% (MDA5), 6.1%/99.0% (HMGCR) and 1.9%/98.5% (SRP). Of all IIM patients, 180/264 tested positive for at least one of the MSAs. In the individual control group, 12/200 (6.0%) tested positive for at least one MSA, most of which had levels close to the cut-off (except one SRP and one PL-12). Only 6/264 (2.3%) IIM patients were positive for more than one antibody (MDA5/HMGCR, EJ/PL-7, 2 x MDA5/TIF1γ, EJ/SAE, SAE/TIF1γ). The overall sensitivity was 68.2% paired with a specificity of 94.0%, leading to an odds ratio of 33.8. The composite scores showed good discrimination between subgroups (e.g., anti-synthetase syndrome). (4) Conclusion: MSA, especially when combined in composite scores (here measured by PMAT), provide value in stratification of patients with IIM.

Highlights

  • Myositis specific (MSA) and myositis associated antibodies (MAA) have been used as an aid in the diagnosis of idiopathic inflammatory myopathies (IIM) for decades [1]

  • Besides immunoprecipitation (IP), mostly line immunoassays (LIA) and dot blot (DB) assays are routinely used for the detection of Myositis specific antibodies (MSA) [6], which are convenient tools for the simultaneous detection of various antibodies, but are accompanied by some limitations [7] including the lack of true quality controls [8], lack of sensitivity [9,10] and specificity (10) for some analytes and subjectivity in interpretation [10,11,12]

  • Since publication of updated new classification criteria for IIM [13,14], a debate has been triggered about the omission of MSA, which was eventually explained by the lack of standardization of autoantibody assays and missing data derived from large multicentric studies [15,16]

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Summary

Introduction

Myositis specific (MSA) and myositis associated antibodies (MAA) have been used as an aid in the diagnosis of idiopathic inflammatory myopathies (IIM) for decades [1]. Besides immunoprecipitation (IP), mostly line immunoassays (LIA) and dot blot (DB) assays are routinely used for the detection of MSA [6], which are convenient tools for the simultaneous detection of various antibodies, but are accompanied by some limitations [7] including the lack of true quality controls [8], lack of sensitivity [9,10] and specificity (10) for some analytes and subjectivity in interpretation [10,11,12]. Since publication of updated new classification criteria for IIM [13,14], a debate has been triggered about the omission of MSA (except anti-Jo-1 antibodies), which was eventually explained by the lack of standardization of autoantibody assays and missing data derived from large multicentric studies [15,16]. The aim of the present study was to evaluate the diagnostic performance of MSA for IIM and in particular for IIM subsets as well as using composite scores derived from a novel particle-based multi-analyte technology (PMAT)

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