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Line blot immunoassays in idiopathic inflammatory myopathies: retrospective review of diagnostic accuracy and factors predicting true positive results To, Fergus; Ventín-Rodríguez, Clara; Elkhalifa, Shuayb; Lilleker, James B; Chinoy, Hector

Abstract

Background: Line blot immunoassays (LIA) for myositis-specific (MSA) and myositis-associated (MAA) autoantibodies have become commercially available. In the largest study of this kind, we evaluated the clinical performance of a widely used LIA for MSAs and MAAs. Methods: Adults tested for MSA/MAA by LIA at a tertiary myositis centre (January 2016–July 2018) were identified. According to expert-defined diagnoses, true and false positive rates were calculated for strongly and weakly positive autoantibody results within three cohorts: idiopathic inflammatory myopathy (IIM), connective tissue disease (CTD) without myositis, and non-CTD/IIM. Factors associated with true positivity were determined. Results: We analysed 342 cases. 67 (19.6%) had IIM, in whom 71 autoantibodies were detected (50 strong positives [70.4%], 21 weak positives [29.6%]). Of the strong positives, 48/50 (96.0%; 19 MSAs, 29 MAAs) were deemed true positives. Of the weak positives, 15/21 (71.4%; 3 MSAs, 12 MAAs) were deemed true positives. In CTD without myositis cases (n = 120), 31/61 (51.0%; 5 MSAs, 26 MAAs) autoantibodies were strongly positive, with 24/31 (77.4%; 0 MSAs, 24 MAAs) true positives. 30/61 (49.2%; 13 MSAs, 17 MAAs) were weakly positive, with 16/30 (53.3%; 0 MSAs, 16 MAAs) true positives. In non-CTD/IIM cases (n = 155), all 24 MSAs and 22 MAAs were false positives; these results included 17 (37.0%; 7 MSAs, 10 MAAs) strong positives. Individual autoantibody specificities were > 98.2 and > 97.5% for weakly and strongly positive results, respectively. True positivity was associated with high pre-test for IIM (odds ratio 50.8, 95% CI 13.7–189.2, p < 0.001) and strong positive (versus weak positive) results (4.4, 2.3–8.3, p < 0.001). Conclusions: We demonstrated the high specificity of a myositis LIA in a clinical setting. However, a significant burden of false positive results was evident in those with a low pre-test likelihood of IIM and for weakly positive autoantibodies.

Item Metadata

Title
Line blot immunoassays in idiopathic inflammatory myopathies: retrospective review of diagnostic accuracy and factors predicting true positive results
Creator
To, Fergus; Ventín-Rodríguez, Clara; Elkhalifa, Shuayb; Lilleker, James B; Chinoy, Hector
Publisher
BioMed Central
Date Issued
2020-07-20
Description
Background: Line blot immunoassays (LIA) for myositis-specific (MSA) and myositis-associated (MAA) autoantibodies have become commercially available. In the largest study of this kind, we evaluated the clinical performance of a widely used LIA for MSAs and MAAs. Methods: Adults tested for MSA/MAA by LIA at a tertiary myositis centre (January 2016–July 2018) were identified. According to expert-defined diagnoses, true and false positive rates were calculated for strongly and weakly positive autoantibody results within three cohorts: idiopathic inflammatory myopathy (IIM), connective tissue disease (CTD) without myositis, and non-CTD/IIM. Factors associated with true positivity were determined. Results: We analysed 342 cases. 67 (19.6%) had IIM, in whom 71 autoantibodies were detected (50 strong positives [70.4%], 21 weak positives [29.6%]). Of the strong positives, 48/50 (96.0%; 19 MSAs, 29 MAAs) were deemed true positives. Of the weak positives, 15/21 (71.4%; 3 MSAs, 12 MAAs) were deemed true positives. In CTD without myositis cases (n = 120), 31/61 (51.0%; 5 MSAs, 26 MAAs) autoantibodies were strongly positive, with 24/31 (77.4%; 0 MSAs, 24 MAAs) true positives. 30/61 (49.2%; 13 MSAs, 17 MAAs) were weakly positive, with 16/30 (53.3%; 0 MSAs, 16 MAAs) true positives. In non-CTD/IIM cases (n = 155), all 24 MSAs and 22 MAAs were false positives; these results included 17 (37.0%; 7 MSAs, 10 MAAs) strong positives. Individual autoantibody specificities were > 98.2 and > 97.5% for weakly and strongly positive results, respectively. True positivity was associated with high pre-test for IIM (odds ratio 50.8, 95% CI 13.7–189.2, p < 0.001) and strong positive (versus weak positive) results (4.4, 2.3–8.3, p < 0.001). Conclusions: We demonstrated the high specificity of a myositis LIA in a clinical setting. However, a significant burden of false positive results was evident in those with a low pre-test likelihood of IIM and for weakly positive autoantibodies.
Subject
Immunoblotting; myositis; autoantibodies; Inflammatory muscle disease; Idiopathic inflammatory myopathy; Line blot immunoassay
Genre
Article
Type
Text
Language
eng
Date Available
2020-07-20
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0392473
URI
http://hdl.handle.net/2429/75224
Affiliation
Medicine, Faculty of; Non UBC; Medicine, Department of; Rheumatology, Division of
Citation
BMC Rheumatology. 2020 Jul 20;4(1):28
Publisher DOI
10.1186/s41927-020-00132-9
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
The Author(s)
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)