Detection of Myositis Autoantibodies by Multi-Analytic Immunoassays in a Large Multicenter Cohort of Patients with Definite Idiopathic Inflammatory Myopathies

Background: The usefulness of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) for the assessment of idiopathic inflammatory myopathies (IIMs) is acknowledged, but laboratory standardization remains a challenge. We detected MSAs/MAAs by multi-analytic line immuno...

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Main Authors: Anna Ghirardello, Mariele Gatto, Chiara Franco, Elisabetta Zanatta, Roberto Padoan, Luana Ienna, Nicoletta Gallo, Margherita Zen, Ingrid E. Lundberg, Michael Mahler, Andrea Doria, Luca Iaccarino
Format: Article
Language:English
Published: MDPI AG 2023-09-01
Series:Diagnostics
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Online Access:https://www.mdpi.com/2075-4418/13/19/3080
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author Anna Ghirardello
Mariele Gatto
Chiara Franco
Elisabetta Zanatta
Roberto Padoan
Luana Ienna
Nicoletta Gallo
Margherita Zen
Ingrid E. Lundberg
Michael Mahler
Andrea Doria
Luca Iaccarino
author_facet Anna Ghirardello
Mariele Gatto
Chiara Franco
Elisabetta Zanatta
Roberto Padoan
Luana Ienna
Nicoletta Gallo
Margherita Zen
Ingrid E. Lundberg
Michael Mahler
Andrea Doria
Luca Iaccarino
author_sort Anna Ghirardello
collection DOAJ
description Background: The usefulness of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) for the assessment of idiopathic inflammatory myopathies (IIMs) is acknowledged, but laboratory standardization remains a challenge. We detected MSAs/MAAs by multi-analytic line immunoassay (LIA) and particle-based multi-analyte technology (PMAT) in a multicenter cohort of patients with IIMs. Methods: We tested the sera from 411 patients affected with definite IIM, including 142 polymyositis (PM), 147 dermatomyositis (DM), 19 cancer-associated myositis, and 103 overlap myositis syndrome (OM), and from 269 controls. MSAs/MAAs were determined by 16Ags LIA in all sera, and anti-HMGCR by ELISA in 157/411 IIM sera and 91/269 control sera. The analytical specificity of LIA/HMGCR ELISA was compared with that of PMAT in 89 MSA+ IIM sera. Results: MSAs/MAAs were positive in 307/411 (75%) IIM patients and 65/269 (24%) controls by LIA (Odds Ratio 9.26, 95% CI 6.43–13.13, <i>p</i> < 0.0001). The sensitivity/specificity of individual MSAs/MAAs were: 20%/100% (Jo-1), 3%/99.3% (PL-7), 4%/98.8% (PL-12), 1%/100% (EJ), 0.7%/100% (OJ), 9%/98% (SRP), 5.6%/99.6% (TIF1γ), 4.6%/99.6% (MDA5), 8%/96% (Mi-2), 1.5%/98% (NXP2), 1.7%/100% (SAE1), 4%/92% (Ku), 8.5%/99% (PM/Scl-100), 8%/96% (PM/Scl-75), and 25.5%/79% (Ro52). Anti-HMGCR was found in 8/157 (5%) IIM patients and 0/176 (0%) controls by ELISA (<i>p</i> = 0.007). Concordance between LIA/HMGCR ELISA and PMAT was found in 78/89 (88%) samples. Individual MSAs detected by LIA were associated with IIM subsets: Jo-1 with PM and OM, PL-12 with OM, Mi-2, TIF1γ, and MDA5 with DM, SRP with PM, and PM/Scl-75/100 with OM (<i>p</i> < 0.001 for all). Conclusions: Since MSAs are mostly mutually exclusive, multi-specific antibody profiling seems effective for a targeted clinical-serologic approach to the diagnosis of IIMs.
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spelling doaj.art-7a4e3f00c310422186ca07e10c3b64382023-11-19T14:14:28ZengMDPI AGDiagnostics2075-44182023-09-011319308010.3390/diagnostics13193080Detection of Myositis Autoantibodies by Multi-Analytic Immunoassays in a Large Multicenter Cohort of Patients with Definite Idiopathic Inflammatory MyopathiesAnna Ghirardello0Mariele Gatto1Chiara Franco2Elisabetta Zanatta3Roberto Padoan4Luana Ienna5Nicoletta Gallo6Margherita Zen7Ingrid E. Lundberg8Michael Mahler9Andrea Doria10Luca Iaccarino11Rheumatology Unit, Department of Medicine-DIMED, University Hospital of Padova, 35128 Padova, ItalyRheumatology Unit, Department of Medicine-DIMED, University Hospital of Padova, 35128 Padova, ItalyRheumatology Unit, Department of Medicine-DIMED, University Hospital of Padova, 35128 Padova, ItalyRheumatology Unit, Department of Medicine-DIMED, University Hospital of Padova, 35128 Padova, ItalyRheumatology Unit, Department of Medicine-DIMED, University Hospital of Padova, 35128 Padova, ItalyRheumatology Unit, Department of Medicine-DIMED, University Hospital of Padova, 35128 Padova, ItalyUnit of Laboratory Medicine, Department of Medicine-DIMED, University Hospital of Padova, 35128 Padova, ItalyRheumatology Unit, Department of Medicine-DIMED, University Hospital of Padova, 35128 Padova, ItalyRheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna, Karolinska Institutet, 171 77 Stockholm, SwedenWerfen Autoimmunity, San Diego, CA 92131, USARheumatology Unit, Department of Medicine-DIMED, University Hospital of Padova, 35128 Padova, ItalyRheumatology Unit, Department of Medicine-DIMED, University Hospital of Padova, 35128 Padova, ItalyBackground: The usefulness of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) for the assessment of idiopathic inflammatory myopathies (IIMs) is acknowledged, but laboratory standardization remains a challenge. We detected MSAs/MAAs by multi-analytic line immunoassay (LIA) and particle-based multi-analyte technology (PMAT) in a multicenter cohort of patients with IIMs. Methods: We tested the sera from 411 patients affected with definite IIM, including 142 polymyositis (PM), 147 dermatomyositis (DM), 19 cancer-associated myositis, and 103 overlap myositis syndrome (OM), and from 269 controls. MSAs/MAAs were determined by 16Ags LIA in all sera, and anti-HMGCR by ELISA in 157/411 IIM sera and 91/269 control sera. The analytical specificity of LIA/HMGCR ELISA was compared with that of PMAT in 89 MSA+ IIM sera. Results: MSAs/MAAs were positive in 307/411 (75%) IIM patients and 65/269 (24%) controls by LIA (Odds Ratio 9.26, 95% CI 6.43–13.13, <i>p</i> < 0.0001). The sensitivity/specificity of individual MSAs/MAAs were: 20%/100% (Jo-1), 3%/99.3% (PL-7), 4%/98.8% (PL-12), 1%/100% (EJ), 0.7%/100% (OJ), 9%/98% (SRP), 5.6%/99.6% (TIF1γ), 4.6%/99.6% (MDA5), 8%/96% (Mi-2), 1.5%/98% (NXP2), 1.7%/100% (SAE1), 4%/92% (Ku), 8.5%/99% (PM/Scl-100), 8%/96% (PM/Scl-75), and 25.5%/79% (Ro52). Anti-HMGCR was found in 8/157 (5%) IIM patients and 0/176 (0%) controls by ELISA (<i>p</i> = 0.007). Concordance between LIA/HMGCR ELISA and PMAT was found in 78/89 (88%) samples. Individual MSAs detected by LIA were associated with IIM subsets: Jo-1 with PM and OM, PL-12 with OM, Mi-2, TIF1γ, and MDA5 with DM, SRP with PM, and PM/Scl-75/100 with OM (<i>p</i> < 0.001 for all). Conclusions: Since MSAs are mostly mutually exclusive, multi-specific antibody profiling seems effective for a targeted clinical-serologic approach to the diagnosis of IIMs.https://www.mdpi.com/2075-4418/13/19/3080myositis-specific antibodiesmyositislaboratory testsline blotmulti-analytic technology
spellingShingle Anna Ghirardello
Mariele Gatto
Chiara Franco
Elisabetta Zanatta
Roberto Padoan
Luana Ienna
Nicoletta Gallo
Margherita Zen
Ingrid E. Lundberg
Michael Mahler
Andrea Doria
Luca Iaccarino
Detection of Myositis Autoantibodies by Multi-Analytic Immunoassays in a Large Multicenter Cohort of Patients with Definite Idiopathic Inflammatory Myopathies
Diagnostics
myositis-specific antibodies
myositis
laboratory tests
line blot
multi-analytic technology
title Detection of Myositis Autoantibodies by Multi-Analytic Immunoassays in a Large Multicenter Cohort of Patients with Definite Idiopathic Inflammatory Myopathies
title_full Detection of Myositis Autoantibodies by Multi-Analytic Immunoassays in a Large Multicenter Cohort of Patients with Definite Idiopathic Inflammatory Myopathies
title_fullStr Detection of Myositis Autoantibodies by Multi-Analytic Immunoassays in a Large Multicenter Cohort of Patients with Definite Idiopathic Inflammatory Myopathies
title_full_unstemmed Detection of Myositis Autoantibodies by Multi-Analytic Immunoassays in a Large Multicenter Cohort of Patients with Definite Idiopathic Inflammatory Myopathies
title_short Detection of Myositis Autoantibodies by Multi-Analytic Immunoassays in a Large Multicenter Cohort of Patients with Definite Idiopathic Inflammatory Myopathies
title_sort detection of myositis autoantibodies by multi analytic immunoassays in a large multicenter cohort of patients with definite idiopathic inflammatory myopathies
topic myositis-specific antibodies
myositis
laboratory tests
line blot
multi-analytic technology
url https://www.mdpi.com/2075-4418/13/19/3080
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