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. 2019 Aug 23:2:100013.
doi: 10.1016/j.jtauto.2019.100013. eCollection 2019 Dec.

Frequencies and clinical associations of myositis-related antibodies in The Netherlands: A one-year survey of all Dutch patients

Anouk C M Platteel  1 , Brigitte A Wevers  2   3   4 , Johan Lim  5 , Jaap A Bakker  6 , Hetty J Bontkes  7 , Joyce Curvers  8 , Jan Damoiseaux  9 , Michiel Heron  10 , Gijs de Kort  11 , Maarten Limper  12 , Ellen G van Lochem  13 , A H Leontine Mulder  14 , Christiaan G J Saris  15 , Hester van der Valk  16 , Anneke J van der Kooi  5 , Ester M M van Leeuwen  4 , Marcel Veltkamp  17   18 , Marco W J Schreurs  19 , Bob Meek  1 , Dörte Hamann  2
Affiliations

Frequencies and clinical associations of myositis-related antibodies in The Netherlands: A one-year survey of all Dutch patients

Anouk C M Platteel et al. J Transl Autoimmun. .

Abstract

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of connective tissue diseases, collectively known as myositis. Diagnosis of IIM is challenging while timely recognition of an IIM is of utter importance considering treatment options and otherwise irreversible (severe) long-term clinical complications. With the EULAR/ACR classification criteria (2017) considerable advancement has been made in the diagnostic workup of IIM. While these criteria take into account clinical parameters as well as presence of one autoantibody, anti-Jo-1, several autoantibodies are associated with IIM and are currently evaluated to be incorporated into classification criteria. As individual antibodies occur at low frequency, the development of line blots allowing multiplex antibody analysis has improved laboratory diagnostics for IIM. The Euroline myositis line-blot assay (Euroimmun) allows screening and semi-quantitative measurement for 15 autoantibodies, i.e. myositis specific antibodies (MSA) to SRP, EJ, OJ, Mi-2α, Mi-2β, TIF1-γ, MDA5, NXP2, SAE1, PL-12, PL-7, Jo-1 and myositis associated antibodies (MAA) to Ku, PM/Scl-75 and PM/Scl-100. To evaluate the clinical significance of detection and levels of these autoantibodies in the Netherlands, a retrospective analysis of all Dutch requests for extended myositis screening within a 1 year period was performed. A total of 187 IIM patients and 632 non-IIM patients were included. We conclude that frequencies of MSA and MAA observed in IIM patients in a routine diagnostic setting are comparable to cohort-based studies. Weak positive antibody levels show less diagnostic accuracy compared to positive antibody levels, except for anti-NXP2. Known associations between antibodies and skin involvement (anti-MDA5, anti-TIF1-γ), lung involvement (anti-Jo-1), and malignancy (anti-TIF1-γ) were confirmed in our IIM study population. The availability of multiplex antibody analyses will facilitate inclusion of additional autoantibodies in clinical myositis guidelines and help to accelerate diagnosing IMM with rare but specific antibodies.

Keywords: Diagnostic parameters; Idiopathic inflammatory myopathies; Multiplex assay; Myositis; Validation.

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Figures

Fig. 1
Fig. 1
Individual frequency per intensity level for IIM and non-IIM for different antibodies as measured with the Euroline myositis line-blot assay (Euroimmun). IIM; idiopathic inflammatory myopathy, MSA; myositis specific antibodies, MAA; myositis associated antibodies. Data is not corrected for multiple antibodies per patient.
Fig. 2
Fig. 2
Heatmap of individual frequency per intensity level for IIM and non-IIM for different antibodies as measured with the Euroline myositis line-blot assay (Euroimmun). IIM; idiopathic inflammatory myopathy, MSA; myositis specific antibodies, MAA; myositis associated antibodies. Data is not corrected for multiple antibodies per patient.
Supplementary Fig. 1
Supplementary Fig. 1
Heatmap of multi-reactive sera within IIM (A) and non-IIM (B) patients. Shown are all sera with two or more specificities. MSA; myositis specific antibodies, MAA; myositis associated antibodies.
See this image and copyright information in PMC

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