Abstract

Background:Adult onset Still’s disease (AOSD) is a rare systemic autoinflammatory disease and joint involvement is one of its clinical manifestations [1]. Arthritis, either oligoarthritis or bilateral symmetrical rheumatoid arthritis-like polyarthritis, is another common clinical feature of AOSD, with a migrating pattern at the beginning and becoming stable over the time [1].Objectives:The aims of the study were to assess joint involvement in AOSD by using magnetic resonance imaging (MRI), to describe main patterns of involvement, and associated clinical characteristics, and to evaluate the global transcriptomic profile of synovial tissues in AOSD to elucidate possible pathogenic pathways involved with.Methods:AOSD patients, who underwent to magnetic resonance imaging (MRI) exam on joints, were assessed to describe patterns of joint involvement and associated clinical characteristics. Some synovial tissues were collected for RNA-sequencing purposes.Results:In this study, 31 patients with AOSD (mean age 42.3 ± 15.2 years, 54.8% male gender), who underwent to at least one MRI exam on joints, were assessed. The most common MRI finding was the presence of synovitis on 60.5%, mainly in peripheral affected joints. MRI revealed a mild to moderate proliferative synovitis, as thickening of the synovial membrane, with low to intermediate signal intensity on T1-weighted images and intermediate to high signal intensity on T2-fat saturated weighted and STIR images, suggesting the presence of a hyperplastic than of a hypertrophied synovial tissue. Bone oedema and bone erosions were reported on 34.9% and 25.6% MRI exams, respectively. In all patients but one, bone erosions were synchronous with bone oedema, overlapping completely the locations. Assessing clinical characteristics in patients with MRI-erosions, a higher prevalence of splenomegaly, a more frequent chronic disease course, lower levels of erythrocyte sedimentation rate and ferritin was observed.Assessing the synovial tissues of some AOSD patients, a moderate perivascular mononuclear infiltrate in the sub-lining stroma of hip synovial tissues was observed, whereas the lining cells were relatively unremarkable. In addition, interleukin (IL)-1β, IL-6, TNF, and heavy ferritin subunit (FeH) were found on AOSD synovial tissues.An RNA-sequencing analysis assessed the global transcriptomic profile of synovial tissues on AOSD patients and matched-controls. Assessing IL-1 pathway, we found an increased expression of il1a, il1b, il1rap, il1r1, il18r1, and Il18bp on AOSD tissues when compared with controls. In IL-6 pathway, we found an increased expression of il6 and il6st/gp130 on AOSD synovial tissues whereas an increased expression of il6r was shown on the controls. Among genes involved in TNF pathway, tnf, traf1, traf2, tnfaip3 and tnfrsf1a resulted to be more expressed in AOSD synovial tissues than in controls. Finally, fth1 and ftl were more expressed in AOSD patients than controls, when we explored the iron uptake and transport pathway.Conclusion:A peculiar MRI pattern of joint involvement in AOSD was reported; the most common finding was the presence of synovitis, characterised by intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. Bone erosions and bone oedema were also observed. This MRI pattern was associated with a hyper-activation of IL-1, IL-6, and TNF pathways together with a hyper-expression of ferritin genes on AOSD synovial tissues.

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