Project description:High expression alleles of the innate cytokine, macrophage migration inhibitory factor (MIF), are associated with the development or the severity of autoimmune inflammatory diseases, including rheumatoid arthritis. Numerous studies support MIF’s role in activating inflammatory pathways and MIF inhibition reduces joint pathology in different experimental models of arthritis. We examined the impact of gene deletion of MIF or its cognate receptor CD74 in the T cell-dependent model of collagen-induced arthritis (CIA) and observed the complete absence of arthritis development, suggesting an unforeseen role for MIF/CD74 signaling in the development of arthritogenic T cells. While MIF has been shown in model systems to contribute to T cell activation by augmenting innate responses, fewer than 1% of T lineage cells express CD74 in naïve spleens and lymph nodes, and its functional consequences in pathogenic T cell subpopulations have not been studied. We found CD74+ T cells to expand during CIA and to increase in number within joint synovium, where they express an effector memory phenotype and recapitulate CIA development upon transfer into naïve mice. We further found evidence for the presence of CD74+ T cells in the circulation and joint synovium of patients with rheumatoid arthritis. MIF-dependent, CD74+ T cells may contribute to the chronicity of rheumatoid synovitis and to disease relapse in previously inflamed joints.
Project description:Pain in rheumatoid arthritis is highly debilitating, impacts quality of life and lacks adequate treatment options. Although the presence of pathogenic autoantibodies and systemic and joint inflammation are distinctive features of the disease, the molecular and neuronal basis of pain remains unclear. Here, we identify the molecular mechanism and causative neurons for autoantibody-induced pain in mice. Single-cell RNA sequencing analysis during arthritis pain revealed interferon-stimulated genes, with a persistent nociceptor neuron sensitization, local inflammation and a causative role of interferons acting on polymodal GFRa3-positive C-fiber-nociceptors, as the origin of pain. Consistently, interferon inhibition blocked gene expression alterations and prevented onset as well as reversed established and residual arthritis pain. The discovered pain-causative mechanism may represent a novel therapeutic approach for treatment of pain in rheumatoid arthritis.
Project description:Genome-wide DNA methylation level was studied to determine whether Rheumatoid arthritis patients (cases) has methylation differences comparing to normal controls in PBLs. We used Illumina HumanMethylation450 BeadChip array to determine the genome-wide DNA methylation difference in PBLs from Rheumatoid arthritis patients (cases) and normal controls Bisulphite converted DNA from the Rheumatoid arthritis patients (cases) and normal controls were hybridized to the Illumina Illumina HumanMethylation450 BeadChip arrays
Project description:Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of unknown etiology and pronounced inter-patient heterogeneity. To characterize RA at the molecular level and to uncover key pathomechanisms, we performed whole-genome gene expression analyses. Synovial tissues from rheumatoid arthritis patients were compared to those from osteoarthritis patients and to normal donors. Keywords: disease state analysis Two disease conditions (rheumatoid arthritis and osteoarthritis) in comparison to normal donors were investigated. For the two disease groups samples derived from three individual patients and two pools of patients were hybridised.
Project description:Intent of this experiment is to define the baseline transcriptome of the synovium obtained from rheumatoid arthritis patients prior to initiation of DMARD (Disease-modifying antirheumatic drug) therapy and compare it with the synovial transcriptome of rheumatoid arthritis patients with an established disease profile.
Project description:Objective: We performed whole-blood transcriptomic profiling for patients with rheumatoid arthritis (RA) who received rituximab (RTX). We aimed to identify a molecular signature that could predict the clinical response to RTX and transcriptomic changes after RTX therapy.
Project description:Rheumatoid arthritis (RA) is a complex and clinically heterogeneous autoimmune disease. Microarray analysis of 83 synovial samples provides insight into the expression-level differences between patients at the site of disease activity. Synovial samples from Rheumatoid Arthritis patients were obtained during joint resection and profiled using microarrays.
