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- Title
TCRβ clones in muscle tissue share structural features in patients with idiopathic inflammatory myopathy and are associated with disease activity.
- Authors
Anang, Dornatien C.; Walter, Hannah A. W.; Lim, Johan; Niewold, Ilse T. G.; van der Weele, Linda; Aronica, Eleonora; Eftimov, Filip; Raaphorst, Joost; van Schaik, Barbera D. C.; van Kampen, Antoine H. C.; van der Kooi, Anneke J.; de Vries, Niek
- Abstract
Objectives: To characterize the T cell receptor (TCRβ) repertoire in peripheral blood and muscle tissues of treatment naïve patients with newly diagnosed idiopathic inflammatory myopathies (IIMs). Methods: High throughput RNA sequencing of the TCRβ chain was performed in peripheral blood and muscle tissue in twenty newly-diagnosed treatment-naïve IIM patients (9 DM, 5 NM/OM, 5 IMNM and 1 ASyS) and healthy controls. Results thereof were correlated with markers of disease activity. Results: Muscle tissue of IIM patients shows more expansion of TCRb clones and decreased diversity when compared to peripheral blood of IIM as well as healthy controls (both p=0.0001). Several expanded TCRb clones in muscle are tissue restricted and cannot be retrieved in peripheral blood. These clones have significantly longer CDR3 regions when compared to clones (also) found in circulation (p=0.0002), while their CDR3 region is more hydrophobic (p<0.01). Network analysis shows that clonal TCRβ signatures are shared between patients. Increased clonal expansion in muscle tissue is significantly correlated with increased CK levels (p=0.03), while it tends to correlate with decreased muscle strength (p=0.08). Conclusion: Network analysis of clones in muscle of IIM patients shows shared clusters of sequences across patients. Muscle-restricted CDR3 TCRβ clones show specific structural features in their T cell receptor. Our results indicate that clonal TCRβ expansion in muscle tissue might be associated with disease activity. Collectively, these findings support a role for specific clonal T cell responses in muscle tissue in the pathogenesis of the IIM subtypes studied.
- Subjects
T cell receptors; TISSUE expansion; MYOSITIS; MUSCLE diseases; MUSCLE strength; T cells; DERMATOMYOSITIS
- Publication
Frontiers in Immunology, 2024, p01
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2023.1279055