Publications by authors named "Timothy Rdj Radstake"
Leflunomide/hydroxychloroquine combination therapy targets type I IFN-associated proteins in patients with Sjögren's syndrome that show potential to predict and monitor clinical response.
RMD Open
August 2023
Objectives: To assess to what extent leflunomide (LEF) and hydroxychloroquine (HCQ) therapy in patients with primary Sjögren's syndrome (RepurpSS-I) targets type I IFN-associated responses and to study the potential of several interferon associated RNA-based and protein-based biomarkers to predict and monitor treatment.
Methods: In 21 patients treated with LEF/HCQ and 8 patients treated with placebo, blood was drawn at baseline, 8, 16 and 24 weeks. IFN-signatures based on RNA expression of five IFN-associated genes were quantified in circulating mononuclear cells and in whole blood.
Objective: Type 2 conventional dendritic cells (cDC2s) are key orchestrators of inflammatory responses, linking innate and adaptative immunity. Here we explored the regulation of immunological pathways in cDC2s from patients with primary Sjögren's syndrome (pSS).
Methods: RNA sequencing of circulating cDC2s from patients with pSS, patients with non-Sjögren's sicca and healthy controls (HCs) was exploited to establish transcriptional signatures.
Objective: The greatest genetic effect reported for systemic sclerosis (SSc) lies in the major histocompatibility complex (MHC) locus. Leveraging the largest SSc genome-wide association study, we aimed to fine-map this region to identify novel human leucocyte antigen (HLA) genetic variants associated with SSc susceptibility and its main clinical and serological subtypes.
Methods: 9095 patients with SSc and 17 584 controls genome-wide genotyped were used to impute and test single-nucleotide polymorphisms (SNPs) across the MHC, classical HLA alleles and their composite amino acid residues.
Article Synopsis
- - The study investigated the effectiveness of Genomic Risk Scores (GRS) in predicting the risk of systemic sclerosis (SSc), using data from a large Genome-Wide Association Study that included over 9,000 SSc patients and 17,000 healthy controls.
- - Researchers developed a GRS that comprised 33 specific genetic variations, demonstrating a reasonable ability to distinguish SSc patients from healthy individuals and other immune-related diseases, achieving an area under the curve (AUC) of 0.673, which improved to 0.787 when combined with other health factors.
- - The findings suggest that GRS can be a valuable tool for early and accurate diagnosis of SSc, although it struggled to differentiate between specific
: Effective treatment for primary Sjögren's syndrome (pSS) is not available. pSS immunopathology involves a variety of immune-cells and dysregulated pathways; targeting several pathways instead of only one could therefore be effective. Treatment with leflunomide (LEF) and hydroxychloroquine (HCQ) might be successful given their unique immunosuppressive properties.
View Article and Find Full Text PDFNeutrophil extracellular traps and low-density granulocytes are associated with the interferon signature in systemic lupus erythematosus, but not in antiphospholipid syndrome.
Ann Rheum Dis
October 2020
Article Synopsis
- The study investigates the role of plasmacytoid dendritic cells (pDCs) in systemic sclerosis (SSc), an autoimmune disease characterized by inflammation and fibrosis, focusing on pathways affecting pDC function.
- Researchers analyzed pDCs from over 1,190 SSc patients and found that lower levels of the transcription factor RUNX3, linked to gene methylation and hypoxia, may contribute to SSc susceptibility.
- The results indicate that loss of RUNX3 in pDCs leads to increased skin fibrosis in mouse models, highlighting pDCs' significant role in the disease's progression and potential therapeutic targets.
Objectives: TYK2 is a common genetic risk factor for several autoimmune diseases. This gene encodes a protein kinase involved in interleukin 12 (IL-12) pathway, which is a well-known player in the pathogenesis of systemic sclerosis (SSc). Therefore, we aimed to assess the possible role of this locus in SSc.
View Article and Find Full Text PDFIntroduction: CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European population.
Methods: A total of seven European populations of Caucasian ancestry were included, comprising 2,131 patients with SSc and 3,966 healthy controls.