Evaluation of a novel particle-based assay for detection of autoantibodies in idiopathic inflammatory myopathies

I Cavazzana; M Richards; C Bentow; A Seaman; M Fredi; M G Giudizi; B Palterer; F Pratesi; P Migliorini; F Franceschini; M Satoh; A Ceribelli; M Mahler

doi:10.1016/j.jim.2019.112661

Evaluation of a novel particle-based assay for detection of autoantibodies in idiopathic inflammatory myopathies

J Immunol Methods. 2019 Nov:474:112661. doi: 10.1016/j.jim.2019.112661. Epub 2019 Aug 21.

Authors

I Cavazzana¹, M Richards², C Bentow³, A Seaman², M Fredi⁴, M G Giudizi⁵, B Palterer⁵, F Pratesi⁶, P Migliorini⁶, F Franceschini⁴, M Satoh⁷, A Ceribelli⁸, M Mahler²

Affiliations

¹ Rheumatology Unit, ASST Spedali Civili, Brescia, Italy.
² Inova Diagnostics, Inc., San Diego, CA, USA.
³ Inova Diagnostics, Inc., San Diego, CA, USA. Electronic address: cbentow@inovadx.com.
⁴ Rheumatology Unit, ASST Spedali Civili, Brescia, Italy; Rheumatology Unit and Chair, Department of Clinical and Experimental Science, University of Brescia, Brescia, Italy.
⁵ Department of Clinical and Experimental Medicine, Unit of Allergology and Clinical Immunology, University of Florence, Florence, Italy.
⁶ Department of Clincial and Experiment Medicine, University of Pisa, Pisa, Italy.
⁷ Department of Clinical Nursing, University of Occupational and Environmental Health, Kitakyushu, Japan.
⁸ BIOMETRA Department, Humanitas Clinical and Research Center - IRCCS, Rozzano, Italy.

PMID: 31442464
DOI: 10.1016/j.jim.2019.112661

Abstract

Background: Myositis specific antibodies (MSA) represent not only important diagnostic tools for idiopathic inflammatory myopathies (IIM), but also help to stratify patients into subsets with particular clinical features, treatment responses, and disease outcome. Consequently, standardization of MSA is of high importance. Although many laboratories rely on protein immunoprecipitation (IP) for the detection of MSA, IP standardization is challenging and therefore reliable alternatives are mandatory. Recently, we identified significant variation between IP and line immunoassay (LIA) for the detection of MSA and myositis associated antibodies. In this study we aimed to compare the results from our previous study to the results obtained with a novel fully automated particle-based technology for the detection of MSA and MAA.

Methods: A total of 54 sera from patients with idiopathic inflammatory myopathy (IIM) were tested using three methods: IP, LIA (Euroimmun, Germany) and a novel particle-based multi-analyte technology (PMAT, Inova Diagnostics, US, research use only). The analysis focused on antibodies to EJ, SRP, Jo-1, NXP-2, MDA5, TIF1-γ, and Mi-2.

Results: Significant variations were observed among all methods. Overall, the novel PMAT assays showed slightly better correlation with IP, but the kappa agreement was strongly dependent on the antibody tested. When the results obtained from IP were used as reference for receiver operating characteristic (ROC) curve analysis, good discrimination and a high area under the curve (AUC) value were found for PMAT (AUC = 0.83, 95% confidence interval, CI 0.70-0.95) which was significantly higher (p = .0332) than the LIA method (AUC = 0.70, 95% CI 0.56-0.84).

Conclusion: The novel PMAT used to detect a spectrum of MSA in IIM represents a potential alternative to IP and other diagnostic assays. Additional studies based on larger cohorts are needed to fully assess the performance of the novel PMAT system for the detection of autoantibodies in myositis.

Keywords: Idiopathic inflammatory myopathies; Immunoprecipitation; Myositis; Myositis specific antibodies; Solid phase assays; Standardization.

Publication types

Comparative Study
Evaluation Study

MeSH terms

Autoantibodies / blood*
Automation, Laboratory
Biomarkers / blood
Humans
Immunoassay*
Immunoprecipitation
Myositis / blood
Myositis / diagnosis*
Myositis / immunology
Predictive Value of Tests
Reproducibility of Results

Substances

Autoantibodies
Biomarkers