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Detection of myositis-specific antibodies
  1. Jean-Baptiste Vulsteke1,
  2. Ellen De Langhe2,3,
  3. Kristl G Claeys4,5,6,
  4. Doreen Dillaerts7,
  5. Koen Poesen8,9,
  6. Jan Lenaerts2,
  7. René Westhovens2,3,
  8. Philip Van Damme4,10,
  9. Daniel Blockmans1,
  10. Petra De Haes11,
  11. Xavier Bossuyt7,9
  1. 1 Department of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium
  2. 2 Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium
  3. 3 Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven, Belgium
  4. 4 Department of Neurology, University Hospitals Leuven, Leuven, Belgium
  5. 5 Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, Leuven, Belgium
  6. 6 Department of Neurology and Institute of Neuropathology, University Hospital RWTH Aachen, Aachen, Germany
  7. 7 Department of Microbiology and Immunology, Experimental Laboratory Immunology, KU Leuven, Leuven, Belgium
  8. 8 Laboratory for Molecular Neurobiomarker Research, KU Leuven, Leuven, Belgium
  9. 9 Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium
  10. 10 Department of Neurosciences, Experimental Neurology, VIB Center for Brain & Disease Research, Laboratory of Neurobiology, KU Leuven, Leuven, Belgium
  11. 11 Department of Dermatology, University Hospitals Leuven, Leuven, Belgium
  1. Correspondence to Dr Xavier Bossuyt, Laboratory Medicine, University Hospitals Gasthuisberg, Leuven 3000, Belgium; xavier.bossuyt{at}uzleuven.be

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It was with much interest that we read the recent European League Against Rheumatism/American College of Rheumatology classification criteria for idiopathic inflammatory myopathies.1 These criteria include Jo-1 autoantibodies, and the authors discussed that future updates of the criteria should also include the more recently identified myositis-specific autoantibodies.1 2 The interest in autoantibodies for classification is also illustrated by a recent proposal for a new clinicoserological classification of adult autoimmune myositis, which is based on the association of autoantibodies with distinct clinical phenotypes.3 4 For example, antibodies to synthetases (eg, Jo-1, PL-7 and PL-12) define the antisynthetase syndrome, anti-MDA-5 antibodies are associated with myositis with overlap features such as interstitial lung disease, anti-TIF-1γ and anti-NXP-2 define a subgroup of dermatomyositis and anti-SRP and anti-HMGCR are associated with necrotising autoimmune myositis.2

As autoantibodies play a role in the newly proposed classifications,1 2 it is expected that measurement of myositis-specific autoantibodies will be increasingly introduced in clinical practice. Most of the myositis-specific autoantibodies have been identified by immunoprecipitation. Alternative, easy-to-use commercial line/dot immunoassays are available. However, such assays are not standardised and may suffer from low specificity.2 Therefore, these assays need to be further validated.

We evaluated a cohort of 144 patients with inflammatory myopathy (IIM) and 240 controls (blood donors, chronic inflammatory demyelinating polyneuropathy, rheumatoid arthritis, systemic sclerosis, Sjögren’s syndrome and systemic lupus erythematosus; 40 of each) for myositis-specific autoantibodies using assays from Alphadia (myositis 12 IgG dot for Bluediver) (Mons, Belgium), Euroimmun (Euroline Autoimmune Inflammatory Myopathies) (Lübeck, Germany) and Trinity Biotech (ImmcoStripe Myositis Advanced LIA) (Buffalo, New York, USA).

The results are shown in table 1. We observed differences in specificity (reactivity in controls) between the manufacturers and between individual antibodies. For example, 2.9% and 2.4% of controls tested positive for anti-Jo-1 by Euroimmun and Trinity, respectively, compared with 0.4% by Alphadia. Overall, Euroimmun and Trinity showed more reactivity in controls than Alphadia, except for anti-SAE for which Euroimmun showed less reactivity in controls. Differences in reactivities between manufacturers were also observed in myositis patients, with the most pronounced difference for anti-TIF-1γ (2.1% with Alphadia versus 12.4% with Euroimmun and 11% with Trinity). It should be noted that even for an established marker such as anti-Jo-1 antibodies, differences between manufacturers were observed in patients with IIM. The likelihood ratio (LR) (prevalence of antibodies in patients divided by prevalence of antibodies in controls) gives a good estimate of how the test result affects the post-test probability (an LR >10 indicates a clinical significant difference in pretest to post-test probability). The LRs are shown in table 1 and further illustrate differences between individual antibodies and between manufacturers.

Table 1

Myositis-specific and myositis-associated antibodies in 144 patients with myositis and in 240 controls

Table 2 shows the corresponding phenotype of myositis-specific antibodies in patients with IIM. The association between antisynthetase antibodies and interstitial lung disease, arthritis and Raynaud’s phenomenon was highly significant for all assays. The association of TIF-1γ antibodies and dermatomyositis was high for two of the three assays tested. The association of other antibodies with certain phenotypes (eg, association of TIF-1γ and NXP-2 with malignancy, of Mi-2 with dermatomyositis, NXP-2 with calcinosis and MDA-5 with amyopathic IIM) were weaker and differed between the assays (table 2), indicating that the assays did not perform similarly.

Table 2

Association of myositis-specific antibodies with clinical phenotype in patients with IIM

Taken together, as myositis-specific autoantibodies are included in classification criteria, it is important that clinicians and laboratory professionals are aware of the performance characteristics of the assays used to detect such antibodies. Initiatives to harmonise assays across manufacturers are needed.

Acknowledgments

We would like to thank Alphadia, Euroimmun and Trinity for providing the reagents to perform this study. PVD holds a senior clinical investigatorship of FWO-Vlaanderen.

References

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Footnotes

  • J-BV and EDL contributed equally.

  • Contributors EDL, J-BV, KGC, KP and XB designed the study. J-BV, DD, EDL and XB analysed the data. DD performed the autoantibody assays. EDL, KGC, PDH, JL, PVD, RW and DB take care of the patients included in the study and revised the manuscript. J-BV, EDL and XB drafted the manuscript.

  • Funding This study was funded by Alphadia, D-tek, Trinity – Immco and Euroimmun.

  • Competing interests None declared.

  • Patient consent Retrospective study using leftover samples.

  • Ethics approval Local Ethics Committee.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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