Trans-omics landscape of systemic vasculitis identified matrix metalloproteinase 12 as a novel signature molecule
Rheumatology, 2025
Matsumoto K., Suzuki K., Magi M., Onishi S., Yoshida H., Takeshita M., Kuramoto J., Yazawa M., Kato T., Shimizu H., Ito T., Yamada S., Sasaki E., Hanaoka K., Noguchi-Sasaki M., Matsumoto Y., Takeuchi T., Kaneko Y.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases | Pathophysiology | Serum |  Olink Target 96 |
Abstract
Objectives
To identify key molecules involved in the disease pathophysiology of systemic vasculitis through trans-omics analysis, with a specific focus on demonstrating matrix metalloproteinase (MMP) 12 as a potential biomarker in rheumatic entities.
Methods
Patients with newly diagnosed or relapsed rheumatic and musculoskeletal diseases from June 2013 until September 2022 were enrolled. We screened vasculitis-specific molecules by combining findings from serum proteome analysis and whole-blood RNA sequencing. We further validated the identified molecules using immunohistochemical staining and spatial transcriptome analysis.
Results
Serum proteome and RNA sequencing identified MMP12 as a significant molecule for 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 could also be used to detect insidious disease activity even under treatment with IL-6 inhibition. Immunohistochemical staining of the affected tissues demonstrated that MMP12 was specifically expressed in tissue-infiltrating CD206-positive macrophages. Spatial transcriptome analysis revealed the characteristic phenotype of MMP12-positive macrophages and its association with macrophage maturation and formation of multinucleated giant cells.
Conclusion
MMP12 is a disease-specific molecule that is associated with macrophage maturation and the formation of multinucleated giant cells and reflects disease activity independently of the IL-6 pathway in systemic vasculitis.