Background/Purpose:  It is preferable to start therapy as early as possible in psoriatic arthritis (PsA) because of the destructive nature of the arthritis.  Starting treatment promptly is complicated because the arthritis component can occur years after the psoriatic skin disease (psoriasis vulgaris, PsV), and the arthritis may not be diagnosed until it is more established.  Many patients with PsV are seen in dermatology clinics where early arthritis symptoms may not be diagnosed. Given these issues, it would be useful to have a predictive model that would allow the identification of patients with PsV that will go on to have PsA, possibly even before clinical symptoms of arthritis are apparent.  Since the psoriasis lesions of the skin are often the first detected symptom of psoriatic disease, molecular profiles of the skin may provide prognostic value to predict the onset of joint inflammation, We conducted a comprehensive genomic and molecular comparison of lesional skin from subjects with PsA and PsV.

Methods:  Lesional psoriatic skin samples were obtained from subjects with PsA (n=6) and PsV (n=10).  PsA subjects were diagnosed by Moll and Wright criteria by a rheumatologist.  PsV samples were chosen after a retrospective chart review was done to assure subjects denied joint complaints at all visits.  Gene expression analysis was conducted using Affymetrix HGU133 2.0+ arrays. Differentially expressed genes (DEGs) were evaluated with a cut-off of fold change >2.0 and false discovery rate <0.01.  Results were validated using RT-PCR.  Ingenuity Pathway Analysis (IPA) was utilized to identify canonical pathways among DEGs.   

Results:  A comparison of PsA and PsV lesional skin revealed 1569 genes were upregulated and 1838 genes were downregulated. While there are a variety of differences in gene expression, it is notable that genes typically associated with bone formation and cartilage were in the top 50 upregulated genes.  These include cartilage oligomeric matrix protein (COMP), secreted frizzled-related protein 1 (SFRP1), and proteoglycan 4 (PRG4).  In addition, IPA showed differential expression of several pathways related to joint destruction and dysregulated bone metabolism.  These include the “Role of Macrophages, Fibroblasts, and Endothelial Cells in Rheumatoid Arthritis”, the “BMP Signaling Pathway”, the “Wnt/ β-Catenin Signaling Pathway” and “RANK Signaling in Osteoclasts”.  RT-PCR confirmed a significant difference in BMP2.

Conclusion:  In this pilot study we show differences in gene expression of lesional skin from subjects with PsA and PsV. To our knowledge, this is the first study to show that markers linked to the joint and dysregulated bone metabolism could be identified in skin biopsies.  This could be useful as both an early predictor of PsV patients who will go on to have PsA and help to guide therapies at a very early stage of disease diagnosis to prevent destructive arthritis.  In addition, this could lead to the discovery of key pathogenic molecules in skin that may affect joints and/or entheses, thus suggesting new therapeutic targets.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/joint-and-bone-related-pathways-discriminate-psoriatic-arthritis-lesional-skin-from-psoriasis-vulgaris-lesional-skin/