Increased Levels of Complement and Immunoglobulins in Dermatomyositis-associated Interstitial Lung Disease

<bold>Background:</bold> Dermatomyositis (DM) associated interstitial lung disease (ILD) has a poor prognosis, especially in patients with anti-melanoma differentiation associated gene 5 (MDA5) autoantibodies. However, the pathogenesis of DM-ILD remains unclear. <bold>Methods:</bold> We investigated lung samples from 18 DM patients and 19 control subjects, and skin biopsy samples from 6 DM patients and 6 control subjects. Specimens were evaluated by immunohistochemical staining with an in-house anti-human MDA5 monoclonal antibody, anti-human immunoglobulin (Ig) G, IgM, IgA, and complement component 3(C3) antibodies. We also established human MDA5 transgenic mice and treated them with rabbit anti-human MDA5 polyclonal antibodies, and evaluated lung injury and Ig and C3 expression. <bold>Results:</bold> In both lung and skin tissues, MDA5 was similarly expressed in DM and control subjects. However, in the lung tissues, DM patients showed significantly higher expression of C3, IgG, and IgM than controls. Furthermore, lung C3 expression was significantly higher in MDA5 autoantibody-positive DM-ILD (n=9) than in autoantibody-negative DM-ILD (n=9). In the skins, C3 and IgM were significantly more expressed in the superficial dermis near the dermoepidermal junction than in controls. In MDA5 transgenic mice, treatment with anti-MDA5 antibody caused lung injury, and high Ig and C3 expression was observed in the lungs of the mice. <bold>Conclusion:</bold> Strong immunoglobulin and C3 expression was expesssed in both lung injury and dermatitis in DM patients. Especially, increased levels of Ig and complement in the lungs, suggesting immune complex formation, may contribute to the poor prognosis of MDA5 autoantibody-positive DM-ILD.