慶應義塾大学医学部内科学教室リウマチ・膠原病内科Lecturer, Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine― 153 ―Systemic vasculitis involves inflammatory and degenerative changes in vascular structures. Disease progression in asymptomatic patients is important, even under inhibition of interleukin (IL)-6. Here, to identify key molecules in the pathophysiology of systemic vasculitis, we performed a trans-omics analysis in patients with newly diagnosed or relapsed rheumatic and musculoskeletal diseases from June 2013 until September 2022. We screened vasculitis-specific molecules by combining findings from serum proteome analysis and whole-blood bulk RNA sequencing, then validated these molecules using immunohistochemical staining and spatial transcriptome analysis. Serum proteome and RNA sequencing identified matrix metalloproteinase (MMP) 12 as significant in systemic vasculitis: it distinguished vasculitis from other rheumatic and musculoskeletal diseases, reflected disease activity along with longitudinal change, and predicted relapse in patients with large-vessel vasculitis. MMP12 also marked insidious disease activity even under treatment with IL-6 inhibition. Immunohistochemistry demonstrated that MMP12 was specifically expressed in tissue-infiltrating CD206-positive histiocytes. Spatial transcriptome analysis revealed the characteristic phenotype of MMP12-positive histiocytes and its association with histiocyte maturation and formation of multinucleated giant cells. MMP12 is a disease-specific molecule that is associated with histiocyte maturation and formation of multinucleated giant cells, and reflects disease activity independently of the IL-6 pathway in systemic vasculitis.Abstract血管炎症定量化を指向した免疫介在性炎症性疾患横断的マルチオミックス解析Development of quantification method for vasculitis using multi-omics approach through rheumatic and musculoskeletal diseases松本 紘太郎Kotaro Matsumoto
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