Project description:The goal of this study was to assess whether the presence of HLA-B*35 contributes to activation of ER stress/UPR and inflammation in lcSScPAH PBMC. HLA-B*35 is associated with increased risk of developing PAH in lcSSc patietns. Also we previously reported that HLA-B*35 induces ECs dysfunction via activation of ER stress/UPR and upregulation of the inflammatory response. Our study demonstrates that HLA-B*35 contributes to the dysregulated expression of selected ER stress, inflammation and proliferation related genes in lcSSc patient PBMCs, as well as healthy individuals, thus supporting a pathogenic role of HLA-B*35 as a risk factor for developing PAH in SSc patients.
Project description:The connective tissue diseases (CTDs) are group of inflammatory disorders with overlapping clinical and serological manifestations. We have undertaken Lupus Extended Phenotype (LEAP) study in of a cohort of adult patients with CTDs, namely systemic lupus erythematosus, Sjogren's syndrome, mixed and undifferentiated CTD, limited and diffuse cutaneous systemic sclerosis and dermatomyositis. RNAseq was undertaken in 12 participants from 4 ‘cohorts’ based on interferon stimulated gene and autoantibodies analyses: 3 ISG positive and anti-Smith positive participants; 3 ISG positive and anti-Smith negative participants; 3 ISG negative and anti-Smith positive participants and 3 ISG negative and anti-Smith negative participants.
Project description:Systemic sclerosis (SSc) is an autoimmune disease characterized by inflammation and fibrosis of the skin and internal organs. We sought to assess the clinical and molecular effects associated with response to intravenous abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc).
Project description:Systemic sclerosis is associated with skin fibrosis thought mediated by TGFb. This open label clinical trial examines the effect of TGFb inhibition on skin gene expression. Patients 1-9 received two doses 1 mg/kg dose of fresolimumab at baseline and 3 weeks; patients 10-19 received a single 5 mg/kg dose Patients with diffuse cutaneous systemic sclerosis within 2 years of first raynauds had skin biopsies before treatment and the 3-4 weeks, 7 weeks and 24 weeks after treatment with fresolimumab
Project description:To assess the safety, efficacy, and molecular change associated with treatment of patients with early, diffuse cutaneous systemic sclerosis (dcSSc) with nilotinib (Tasigna™).
Project description:To clarify the characteristics of CEACAM-positive monocytes in systemic sclerosis (SSc), we performed gene expression microarrays between CEACAM-positive and CEACAM-negative classical monocytes from diffused cutaneous systemic sclerosis(dcSSc) patients. We further analyzed expression levels of each subtype of CEACAM on monocytes from dcSSc by flow cytometry and performed gene expression microarrays between CEACAM1+CEACAM6- and CEACAM1-CEACAM6+ monocytes.
Project description:To clarify the characteristics of CEACAM-positive monocytes in systemic sclerosis (SSc), we performed gene expression microarrays between CEACAM-positive and CEACAM-negative classical monocytes from diffused cutaneous systemic sclerosis(dcSSc) patients. We further analyzed expression levels of each subtype of CEACAM on monocytes from dcSSc by flow cytometry and performed gene expression microarrays between CEACAM1+CEACAM6- and CEACAM1-CEACAM6+ monocytes.
Project description:Gene expression from human keratinocytes isolated from limited systemic sclerosis (lcSSc) and diffuse systemic sclerosis (dcSSc) skin biopsy
