Enhanced Type 1 Interferon Signature in Axial Spondyloarthritis Patients Unresponsive to Secukinumab Treatment.
Arthritis Rheumatol
; 2024 Aug 19.
Article
en En
| MEDLINE
| ID: mdl-39160761
ABSTRACT
OBJECTIVE:
Axial spondyloarthritis (axSpA) is an inflammatory disease in which overactive IL-17A-producing cells are implicated in a central role. Therapeutically, biologics that target IL-17A, such as secukinumab, have demonstrated improved clinical outcomes. Despite this translational success, there is a gap in understanding why some axSpA patients do not respond to IL-17A blocking therapy. Our study aims to discriminate immune profiles between secukinumab responders (SEC-R) and nonresponders (SEC-NR).METHODS:
Peripheral blood mononuclear cells were collected from 30 axSpA patients before and 24-weeks after secukinumab treatment. Frequency of CD4+ subsets were compared between SEC-R and SEC-NR using flow cytometry. Mature CD45RO+CD45RA-CD4+ T cells were FACS sorted, and RNA was measured using NanoString analysis.RESULTS:
SEC-NR had an increased frequency of IL-17A-producing RORγt+CD4+ T cells compared to HCs at pre-secukinumab (p<0.01). SEC-NR had a significant increase of CXCR3+ CD4+ T cells pre-secukinumab compared to SEC-R (p<0.01). Differentially expressed gene analysis revealed upregulation of type 1 interferon-regulated genes in SEC-NR patients compared to SEC-R post-biologic. SEC-R patients had an upregulated cytotoxic CD4+ T cell gene signature pre-secukinumab compared to SEC-NR patients.CONCLUSIONS:
The increased frequency of IL-17A-producing cells in SEC-NR patients suggests a larger inflammatory burden than SEC-R patients. With treatment, SEC-NR patients have a more pronounced type 1 IFN signature than SEC-R patients, suggesting a mechanism contributing to this larger inflammatory burden. The results point toward more immune heterogeneity in axSpA than has been recognized and highlights the need for precision therapeutics in this disease.
Texto completo:
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Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Arthritis Rheumatol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Canadá