JDM and juvenile overlap myositis represent heterogeneous subtypes of juvenile idiopathic inflammatory myopathy (JIIM). Chronic evolution can occur in up to 60% of cases, and morbidity/mortality is substantial. We aimed to describe the clinical, biological, histological and type I IFN status in JIIM associated with anti-melanoma differentiation-associated protein 5 (anti-MDA5) autoantibodies at presentation (group 1) in comparison with other JIIM (group 2).
This was a retrospective and prospective study of patients with JIIM ascertained from three French paediatric rheumatology reference centres between 2013 and 2019. Muscle biopsies were reviewed. Type I interferon pathway activity was assessed by dosage of IFNα serum protein and the expression of IFN-stimulated genes.
Sixty-four patients were included, 13 in group 1 (54% JDM and 46% juvenile overlap myositis) and 51 in group 2 (76% JDM and 24% juvenile overlap myositis). Group 1 patients demonstrated more arthritis, skin ulcerations, lupus features and interstitial lung disease, and a milder muscular involvement. Serum IFNα levels were higher in group 1 than 2, and decreased after treatment or improvement in both groups. Outcome was similar in both groups. Unconventional treatment (more than two lines) was required in order to achieve remission, especially when skin ulceration was reported.
This study indicates a higher frequency of arthritis, skin ulcerations and interstitial lung disease, but milder muscular involvement, in JIIM with positive anti-MDA5 autoantibodies compared with other JIIM. Our data support an important role of systemic IFNα in disease pathology, particularly in the anti-MDA5 auto-antibody-positive subgroup. In severe and refractory forms of JIIM, IFNα may represent a therapeutic target.
MDA5 autoantibody assessment
Dot or line immunoassays [Euroline autoimmune inflammatory myopathies 16 antigens (Euroimmun, Lübeck, Germany) and Myositis profile 12 (D-TEK, Mons, Belgium)] were used to qualitatively detect the presence of anti-MDA5 autoantibodies in all the patients at the onset of the disease. The MDA5 Photonic Immunoassay (PRI, Genalyte Inc.) enables the detection of Ig autoantibodies recognizing MDA5 antigen using whole blood or serum. The MDA5 PRI assay is based on the Maverick™ Detection System (Genalyte, Inc., USA), which performs multiplexed detection of autoantibody binding events by measuring the shift in wavelength of ring resonance as the antibodies bind to the antigens on the surface above the rings. For each sample, an aliquot of whole blood (10 µl) or serum (5 µl) is mixed with 250 µl of diluent in the sample well of the consumable array, which is then placed in the Maverick instrument. The change in the resonant wavelength, expressed in Genalyte Response Units (GRU), is proportional to the mass bound above the ring resonators. This technique was used to assess MDA5 autoantibodies longitudinally in our cohort. A specific cut-off in GRU has been determined with <10 GRU negative, 10–20 GRU indeterminate and >20 GRU positive [32, 33].