Targeting interferon responses in juvenile dermatomyositis: Siglec-1 as an in vitro biomarker for JAK inhibitor efficacy.

ABSTRACT:

Objectives

For IFN-driven diseases, such as juvenile dermatomyositis (JDM), there is a critical need for targeted therapies. We aimed to develop an in vitro model, using Siglec-1 as read-out, to evaluate inhibition of IFN-mediated responses with different JAK inhibitors (JAKi).

Methods

Healthy donor (HD) PBMCs were cultured with type I and II IFNs, TLR agonists and plasma or serum from patients (JDM, DM, JSLE, COVID-19) and HDs. Siglec-1 expression on CD14+ monocytes was analyzed using flow cytometry. Inhibitory assays involved pre-incubation with JAKi (filgotinib, tofacitinib, baricitinib, ruxolitinib, deucravacitinib) and interferon-α/β receptor (IFNAR)-blocking antibody. Correlations between plasma-induced Siglec-1 levels and clinical disease activity were analyzed in JDM

SUBMITTER: Veldkamp SR 

PROVIDER: S-EPMC12407234 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature