Abstract
BackgroundPsoriatic arthritis (PsA) is an inflammatory arthritis whose pathogenesis is poorly understood; it is characterized by bone erosions and new bone formation. The diagnosis of PsA is mainly clinical and diagnostic biomarkers are not yet available. The aim of this work was to clarify some aspects of the disease pathogenesis and to identify specific gene signatures in paired peripheral blood cells (PBC) and synovial biopsies of patients with PsA. Moreover, we tried to identify biomarkers that can be used in clinical practice.MethodsPBC and synovial biopsies of 10 patients with PsA were used to study gene expression using Affymetrix arrays. The expression values were validated by Q-PCR, FACS analysis and by the detection of soluble mediators.ResultsSynovial biopsies of patients showed a modulation of approximately 200 genes when compared to the biopsies of healthy donors. Among the differentially expressed genes we observed the upregulation of Th17 related genes and of type I interferon (IFN) inducible genes. FACS analysis confirmed the Th17 polarization. Moreover, the synovial trascriptome shows gene clusters (bone remodeling, angiogenesis and inflammation) involved in the pathogenesis of PsA. Interestingly 90 genes are modulated in both compartments (PBC and synovium) suggesting that signature pathways in PBC mirror those of the inflamed synovium. Finally the osteoactivin gene was upregulared in both PBC and synovial biopsies and this finding was confirmed by the detection of high levels of osteoactivin in PsA sera but not in other inflammatory arthritides.ConclusionsWe describe the first analysis of the trancriptome in paired synovial tissue and PBC of patients with PsA. This study strengthens the hypothesis that PsA is of autoimmune origin since the coactivity of IFN and Th17 pathways is typical of autoimmunity. Finally these findings have allowed the identification of a possible disease biomarker, osteoactivin, easily detectable in PsA serum.
Highlights
Psoriatic arthritis (PsA) is primarily characterised by enthesitis and by synovitis, leading to bone erosions and new bone formation [1]; 10% to 30% of patients with skin psoriasis are affected by the disease, with an estimated prevalence of 1%.Genetic studies indicate that PsA has a heritable component [2] and many genes have been implicated in psoriasis and PsA [3]
The osteoactivin gene was upregulared in both peripheral blood cells (PBC) and synovial biopsies and this finding was confirmed by the detection of high levels of osteoactivin in PsA sera but not in other inflammatory arthritides
We describe the first analysis of the trancriptome in paired synovial tissue and PBC of patients with PsA
Summary
Psoriatic arthritis (PsA) is primarily characterised by enthesitis and by synovitis, leading to bone erosions and new bone formation [1]; 10% to 30% of patients with skin psoriasis are affected by the disease, with an estimated prevalence of 1%.Genetic studies indicate that PsA has a heritable component [2] and many genes have been implicated in psoriasis and PsA [3]. Psoriatic arthritis (PsA) is primarily characterised by enthesitis and by synovitis, leading to bone erosions and new bone formation [1]; 10% to 30% of patients with skin psoriasis are affected by the disease, with an estimated prevalence of 1%. Magnetic resonance imaging (MRI) is able to detect joint damage earlier and to assess the extent of joint involvement more accurately than plain radiographs. MRI and scintigraphy can be used for an early detection of sacroiliitis and axial disease In addition these imaging techniques are widely used to evaluate the efficacy of novel therapies for PsA [8,9]. The aim of this work was to clarify some aspects of the disease pathogenesis and to identify specific gene signatures in paired peripheral blood cells (PBC) and synovial biopsies of patients with PsA. We tried to identify biomarkers that can be used in clinical practice
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