Myositis Autoantibodies: A Comparison of Results From the Oklahoma Medical Research Foundation Myositis Panel to the Euroimmun Research Line Blot

Mecoli, Christopher A.; Albayda, Jemima; Tiniakou, Eleni; Paik, Julie J; Zahid, Umar; Danoff, Sonye K.; Casciola‐Rosen, Livia; Casal-Domínguez, María; Pak, Katherine; Pinal‐Fernandez, Iago; Mammen, Andrew L.; Christopher‐Stine, Lisa

doi:10.1002/art.41088

Cited by 39 publications

(41 citation statements)

References 7 publications

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“…To increase clinical specificity and PPV, a recent study suggested excluding MSA with a low-positive signal intensity. 15,17,18 However, ROC analysis of our data revealed that higher cut-offs had a lower clinical sensitivity without increasing clinical specificity. This could be due to the low number of MSA/MAA positive IIM patients identified in our cohort.…”

Section: Discussionmentioning

confidence: 66%

The use and diagnostic value of testing myositis-specific and myositis-associated autoantibodies by line immuno-assay: a retrospective study

Lackner

Tiefenthaler

Mirzayeva

et al. 2020

Therapeutic Advances in Musculoskeletal

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Aims: Line immune-assays (LIA) for the detection of myositis-specific antibodies (MSA) are used widely for characterization of idiopathic inflammatory myopathies (IIM). Their current use and significance for the diagnosis of IIM remains unclear. Methods: In this retrospective analysis, we retrieved clinical diagnoses of patients tested for MSA and myositis-associated antibodies (MAA) Jo-1, Mi-2α, Mi-2β, TIF1γ, SRP, MDA-5, NXP-2, SAE, PL-7, PL-12, EJ, OJ, PM-Scl100, PM-Scl75 and Ku. We calculated clinical specificity, clinical sensitivity, negative- and positive predictive values (PPV) as well as positive and negative likelihood ratios. Results: In total, we analyzed 3167 samples. After exclusion of repeated measurements and patients with insufficient clinical information, data of 1118 patients were available for analysis. A total of 242 patients tested positive for at least one antibody, of which 45 patients had a diagnosis of IIM; 25 IIM patients were negative for all MSA/MAA. Clinical specificity of MSA/MAA for the diagnosis of IIM ranged between 94.2% and 99.9%. Clinical sensitivity and PPV across all antibodies tested ranged from 0.0% to 12.9% and 0.0% to 72.7%, respectively. Conclusion: In clinical practice MSA/MAA are used widely for diagnostic work-up of IIM, resulting in a low pre-test probability. Clinicians should be aware that PPVs for most MSA/MAA are low.

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Section: Discussionmentioning

confidence: 66%

The use and diagnostic value of testing myositis-specific and myositis-associated autoantibodies by line immuno-assay: a retrospective study

Lackner

Tiefenthaler

Mirzayeva

et al. 2020

Therapeutic Advances in Musculoskeletal

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“…Weak positive anti-SRP had the lowest specificity. Our results suggest that this LIA’s accuracy may be improved if the threshold for defining weak positivity was increased, although this may vary according to each antibody on the assay [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Line blot immunoassays in idiopathic inflammatory myopathies: retrospective review of diagnostic accuracy and factors predicting true positive results

Ventín-Rodríguez

Elkhalifa

et al. 2020

BMC Rheumatol

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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.

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“…Early studies also suggested that, the Euroline line blot assay, which detects anti-Mi-2α and anti-Mi-2β separately, is fraught with false positives. It has more recently been confirmed that, using the Euroline, anti-Mi-2α is sensitive and specific, but anti-Mi-2β suffers from lower sensitivity and much lower specificity (154,155). It was suggested that more stringent cutoff values would improve the performance of the line assay, but this was not helpful for the performance for anti-TIF-1γ, and obviously would not ameliorate instances where sensitivity is already a problem (156,157).…”

Section: The Critical Importance Of Autoantibody Assay Platform In Interpreting Autoantibody Significancementioning

confidence: 99%

“…In order to test and validate assays, large populations of patients likely positive for the antibody in question are needed in addition to negative controls (153). Carefully defined cutoffs for assigning positive antibody status are also needed for each assay (155,168).…”

Section: Increasing the Utility Of The Msas: Define The Patient Populationmentioning

confidence: 99%

Dermatomyositis autoantibodies: how can we maximize utility?

Hodgkinson¹,

Wu²,

Fiorentino³

2021

Ann Transl Med

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The past 15 years has seen significant advances in the characterization of myositis-specific autoantibodies (MSAs) and their associated phenotypes in patients with dermatomyositis (DM). As more careful studies are performed, it is clear that unique combinations of clinical and pathological phenotypes are associated with each MSA, despite the fact that there is considerable heterogeneity within antibody classes as well as overlap across the groups. Because risk for interstitial lung disease (ILD), internal malignancy, adverse disease trajectory, and, potentially response to therapy differ by DM MSA group, a deeper understanding of MSAs and validation and standardization of assays used for detection are critical for optimizing diagnosis and treatment. Like any test, the diagnostic sensitivity and specificity of assays for various MSAs is not perfect. Currently tests for MSAs are helpful at minimum for a clinician to assess relative risk or contribute to diagnosis and perhaps counsel the appropriate patient about what to expect.With international standardization and larger studies it is likely that more antibody tests will make their way into formal schemata for diagnosis and actionable risk assessment in DM. In this review, we summarize key considerations for interpreting the clinical and pathologic associations with MSA in DM and identify critical gaps in knowledge and practice that will maximize their clinical utility and utility for understanding disease pathogenesis.

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Myositis Autoantibodies: A Comparison of Results From the Oklahoma Medical Research Foundation Myositis Panel to the Euroimmun Research Line Blot

Cited by 39 publications

References 7 publications

The use and diagnostic value of testing myositis-specific and myositis-associated autoantibodies by line immuno-assay: a retrospective study

The use and diagnostic value of testing myositis-specific and myositis-associated autoantibodies by line immuno-assay: a retrospective study

Line blot immunoassays in idiopathic inflammatory myopathies: retrospective review of diagnostic accuracy and factors predicting true positive results

Dermatomyositis autoantibodies: how can we maximize utility?

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