TCRß clones in muscle tissue share structural features in patients with idiopathic inflammatory myopathy and are associated with disease activity.
Front Immunol
; 14: 1279055, 2023.
Article
en En
| MEDLINE
| ID: mdl-38268914
ABSTRACT
Objectives:
To characterize the T cell receptor (TCRß) 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 TCRß 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 TCRß clones and decreased diversity when compared to peripheral blood of IIM as well as healthy controls (both p=0.0001). Several expanded TCRß 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 TCRß 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 TCRß clones show specific structural features in their T cell receptor. Our results indicate that clonal TCRß 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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Músculos
/
Miositis
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Front Immunol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Países Bajos