Assessing the sensitivity and specificity of myositis-specific and associated autoantibodies: a sub-study from the MyoCite cohort

Aravinthan Loganathan; Latika Gupta; Alex Rudge; Hui Lu; Elizabeth Bowler; Fionnuala McMorrow; R Naveen; Anamika K Anuja; Vikas Agarwal; Neil McHugh; Sarah Tansley

doi:10.1093/rheumatology/keae167

Assessing the sensitivity and specificity of myositis-specific and associated autoantibodies: a sub-study from the MyoCite cohort

Rheumatology (Oxford). 2024 Mar 13:keae167. doi: 10.1093/rheumatology/keae167. Online ahead of print.

Authors

Aravinthan Loganathan^{1

2}, Latika Gupta^{3

4

5}, Alex Rudge⁶, Hui Lu², Elizabeth Bowler², Fionnuala McMorrow², R Naveen³, Anamika K Anuja³, Vikas Agarwal³, Neil McHugh², Sarah Tansley^{1

2}

Affiliations

¹ Royal National Hospital for Rheumatic Diseases, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK.
² Department of Life Sciences, University of Bath, Bath, UK.
³ Department of Clinical Immunology and Rheumatology, SGPGIMS, Lucknow, India.
⁴ Department of Rheumatology, Royal Wolverhampton Hospital NHS Trust, Wolverhampton, UK.
⁵ Division of Musculoskeletal and Dermatological Sciences, Centre for Musculoskeletal Research, School of Biological Sciences, The University of Manchester, Manchester, UK.
⁶ Department of Mathematical Sciences, University of Bath, Bath, UK.

PMID: 38479813
DOI: 10.1093/rheumatology/keae167

Abstract

Objectives: Myositis-specific and associated autoantibodies are important biomarkers in routine clinical use. We assessed local testing performance for myositis autoantibodies by comparing line immunoassay (LIA) to protein radio-immunoprecipitation and identifying clinical characteristics associated with each myositis autoantibody in the MyoCite cohort.

Methods: Serum samples from patients within the MyoCite cohort, a well-characterised retro-prospective dataset of adult and juvenile idiopathic inflammatory myopathy (IIM) patients in Lucknow, India (2017-2020), underwent LIA at Sanjay Gandhi Postgraduate Institute of Medical Science (SGPGIMS), Lucknow. Immunoprecipitation of 147 IIM patient serum samples (125 adult-onset, 22 juvenile-onset) was conducted at the University of Bath, with researchers blind to LIA results. LIA performance was assessed against Immunoprecipitation as the reference standard, measuring sensitivity, specificity, and inter-rater agreement. Univariate and multivariate logistic regression determined clinical associations for specific MSA.

Results: Immunoprecipitation identified myositis autoantibodies in 56.5% (n = 83) of patient samples, with anti-Jo1 (n = 16; 10.9%) as the most common, followed by anti-MDA5 (n = 14, 9.5%). While LIA showed good agreement for anti-Jo1, anti-PL7 and anti-PL12 (Cohen's κ 0.79, 0.83, and 1, respectively), poor agreement was observed in other subgroups, notably anti-TIF1γ (Cohen's κ 0.21). Strongly positive samples, especially in myositis-specific autoantibodies, correlated more with immunoprecipitation results. Overall, 59 (40.1%) samples exhibited non-congruence on LIA and Immunoprecipitation, and κ values for LIA's for anti-TIF1γ, anti-Ku, anti-PmScl, anti-Mi2, and anti-SAE ranged between 0.21-0.60.

Conclusion: While LIA reliably detected anti-Jo1, anti-PL7, anti-PL12, anti-MDA5, and anti-NXP-2, it also displayed false positives and negatives. Its effectiveness in detecting other autoantibodies, such as anti-TIF1γ, was poor.

Keywords: Indian population; autoantibodies; dermatomyositis; immunoprecipitation clinical associations; inflammatory myositis; juvenile dermatomyositis; polymyositis.