Clinical characteristics and risk factors associated with bone erosion in patients with tophi.

INTRODUCTION: If a large amount of urate crystals is deposited in a joint cavity for an extended period of time, bone erosion will occur and gradually cause skeletal muscle necrosis and joint deformity. The aim of this study was to describe the clinical characteristics and factors associated with bone erosion in gout patients with tophi. METHODS: A total of 210 gout patients with tophi were enrolled and divided into a bone erosion group (n = 135) and a non-bone erosion group (n = 75). Digital radiography (DR) was performed to detect bone erosion in the elbow, wrist, knee, ankle joints, interphalangeal and metatarsophalangeal joints. The clinical characteristics were recorded and compared between the two groups. Multivariate logistic regression analysis was conducted to explore the factors associated with bone erosion. RESULTS: Compared with the non-bone erosion group, the bone erosion group had an older age, longer disease duration of gout and tophi, higher level of serum creatinine (sCr), higher proportion of drinking history and ulceration, and a lower glomerular filtration rate (GFR). Univariate logistic regression analysis results showed that sex, age, body mass index (BMI), gout duration, tophi duration, GFR, white blood cell (WBC) count, sCr level, smoking history, drinking history, and presence of ulceration were associated with bone destruction. Multivariable logistic regression analysis results indicated that tophi duration, drinking history, ulceration and sCr were positively and independently related to bone erosion. CONCLUSIONS: Tophi patients with bone erosion presented different clinical characteristics. Tophi duration, drinking history, ulceration and sCr were associated with bone erosion in gout patients with tophi.

LncRNA expression profiling in exosomes derived from synovial fluid of patients with rheumatoid arthritis.

OBJECTIVE: To identify the long non-coding RNA (lncRNA) expression profiling in exosomes derived from synovial fluid of rheumatoid arthritis (RA) patients, and carry out bioinformatics analysis on target genes of differentially expressed lncRNAs. METHODS: Exosomes were isolated from synovial fluid via ultracentrifugation. RNAs were extracted from exosomes by using HiPure Liquid RNA/miRNA kits, followed by lncRNA sequencing. Differentially expressed lncRNAs in RA were screened, and bioinformatics analysis of their target genes was carried out. qRT-PCR was used to verify the lncRNA expression levels. RESULTS: Compared with osteoarthritis (OA), 347 lncRNAs were found differentially expressed in RA. Compared with gout, 805 lncRNAs were found differentially expressed in RA. Compared with both OA and gout, 85 lncRNAs were found specially expressed in RA (65 were upregulated (including ENST00000433825.1)). Functional analysis of target genes of the specially expressed lncRNAs revealed significant enrichment of "autophagy" and "mTOR signaling pathway". The qRT-PCR results indicated that ENST00000433825.1 was highly expressed in RA, compared with both OA and gout (P < 0.05), which matched the lncRNA sequencing results. Correlation analysis showed that the level of ENST00000433825.1 in RA patients was significantly and positively correlated with the level of C-reactive protein (CRP) (P < 0.001). CONCLUSIONS: The lncRNA expression profiling in exosomes derived from synovial fluid of RA was significantly different from OA and gout. ENST00000433825.1 was highly and uniquely expressed in RA and significantly and positively correlated with CRP, which might provide a diagnostic and therapeutic biomarker for RA.

Proteomics profiling of CD4 + T-cell-derived exosomes from patients with rheumatoid arthritis.

OBJECTIVES: Our study profiled the CD4 + T-cell-derived exosomes from patients with rheumatoid arthritis (RA) using proteomics. METHODS: Proteomic analysis of CD4 + T-cell-derived exosomes was performed by tandem mass tags (TMT) combined with LC-MS/MS. We validated the most significantly upregulated and downregulated proteins using ELISA and WB. RESULTS: The proteomic results showed that there were 3 upregulated differentially expressed proteins and 31 downregulated differentially expressed proteins in the RA group. The results indicated that dihydropyrimidinase-related protein 3 (DPYSL3) was significantly upregulated in CD4 + T-cell-derived exosomes, whereas proteasome activator complex subunit 1 (PSME1) was significantly downregulated in the RA group. Bioinformatics analysis showed that proteins were enriched in "positive regulation of gene expression", "antigen processing and presentation", "acute-phase response" and "PI3K-AKT signaling" pathways. ELISA verified that compared to the control group, the RA group showed significant upregulation of DPYSL3, and downregulation of PSME1 in CD4 + T-cell-derived exosomes. CONCLUSIONS: The proteomic analysis results of CD4 + T-cell-derived exosomes from patients with RA suggest that these differentially expressed proteins may be involved in RA pathogenesis. DPYSL3 and PSME1 may become useful biomarkers for RA.

TMT-Based Quantitative Proteomics Analysis of Synovial Fluid-Derived Exosomes in Inflammatory Arthritis.

Objectives: To compare the proteomics of synovial fluid (SF)-derived exosomes in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), gout, and osteoarthritis (OA) patients. Methods: Exosomes were separated from SF by the Exoquick kit combined ultracentrifugation method. Tandem mass tags (TMT)-labeled liquid chromatography mass spectrometry (LC-MS/MS) technology was used to analyze the proteomics of SF-derived exosomes. Volcano plot, hierarchical cluster, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Results: A total of 1,678 credible proteins were detected. Sixty-nine differentially expressed proteins were found in gout, compared with OA, axSpA, and RA simultaneously. Twenty-five proteins were found highly expressed in gout uniquely, lysozyme C and protein S100-A9 included, whose bioinformatic analysis was significantly involved in "neutrophil degranulation" and "prion diseases". Eighty-four differentially expressed proteins were found in axSpA, compared with OA, gout, and RA simultaneously. Thirty-nine proteins were found highly expressed in axSpA uniquely, RNA-binding protein 8A and protein transport protein Sec24C included, whose bioinformatic analysis was significantly involved in "acute-phase response" and "citrate cycle". One hundred and eighty-four differentially expressed proteins were found in RA, compared with OA, gout, and axSpA simultaneously. Twenty-eight proteins were found highly expressed in RA uniquely, pregnancy zone protein (PZP) and stromelysin-1 included, whose bioinformatic analysis was significantly involved in "serine-type endopeptidase inhibitor activity" and "complement and coagulation cascades". Enzyme-linked immunosorbent assay (ELISA) result showed that the exosome-derived PZP level of SF in RA was higher than that in OA (p < 0.05). Conclusion: Our study for the first time described the protein profiles of SF-derived exosomes in RA, axSpA, gout, and OA patients. Some potential biomarkers and hypothetical molecular mechanisms were proposed, which may provide helpful diagnostic and therapeutic insights for inflammatory arthritis (IA).