Abstract
Spondyloarthritis (SpA) is characterized by chronic inflammation and structural damage involving spine and peripheral joints. Monocytes, as part of innate immune system, following migration into affected tissue, may play a role in the pathogenesis of SpA. Here, potential associations between osteogenesis-linked gene expression profile in particular monocyte subpopulations and clinical signs of SpA were investigated. The 20 patients with axial and 16 with peripheral SpA were enrolled in the study. Monocyte subpopulations (classical—CD14++CD16−, intermediate—CD14++CD16+ and non-classical—CD14+CD16++) were isolated from blood using flow cytometry and gene expression analysis was performed using real-time PCR method and TaqMan Array, Human Osteogenesis, Fast 96-well plates. Next, the characteristic clinical features shared by axial and peripheral SpA were analyzed in the context of the expression of selected genes in the three subpopulations of monocytes. We demonstrated that expression of VEGFA in classical and MSX2 in non-classical monocytes were associated with the number of swollen and painful peripheral joints of SpA patients. We conclude that monocytes may contribute to the development of peripheral arthritis in SpA patients. This might be possible through subpopulation specific effects, linking number of inflamed joints with expression of VEGFA in classical monocytes and MSX2 in non-classical monocytes.
Highlights
Spondyloarthritis (SpA) represents a group of second most prevalent inflammatory rheumatic disorders[1] characterized by chronic inflammation and structural damage involving axial and peripheral skeleton
There is a proposal to define SpA by its pathophysiology rather than by its phenotypic presentation, since the emerging data from immunopathology studies and clinical trials suggest that axial and peripheral spondyloarthritis might be driven by different mechanisms and respond differently to treatment, supporting the classification of SpA according to the presence of axial or peripheral d isease[2]
We found Vascular Endothelial Growth Factor A (VEGFA) mRNA in classical monocytes to be positively associated with measurement of joint involvement, i.e. number of swollen joints from total joint count and number of swollen and painful joints from DAS28 score, with False Discovery Rate (FDR) < 0.05 for each feature
Summary
Spondyloarthritis (SpA) represents a group of second most prevalent inflammatory rheumatic disorders (ca. 0.2–1.6% depending on geographic area)[1] characterized by chronic inflammation and structural damage involving axial and peripheral skeleton. All phenotypes share similar axial (sacroiliitis, spondylitis, back pain) or peripheral (arthritis, enthesitis, dactylitis) manifestations, and SpA might be classified as one of two subforms with different pathophysiology, with predominant involvement of axial or peripheral s keleton[1]. It is interesting to explore mechanisms leading to SpA manifestations shared by axSpA and pSpA They are likely to be most variable and at the same time most informative at an early stage of the disease. We focused on the manifestations which could be expressed both in axSpA and pSpA—i.e. arthritis, enthesitis, dactylitis and inflammatory back pain This might help to understand how monocytes and possibly derived from them macrophages and osteoclasts might drive particular pathological processes, which are interpreted as characteristic clinical signs of both axSpA and pSpA
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