SLAMF8 as a potential biomarker for rheumatoid arthritis identified by comparing peripheral blood mononuclear cells,fibroblast-like synoviocytes,and synovial tissue using bioinformatics analysis

Background::Rheumatoid arthritis(RA)is a chronic autoimmune inflammatory disease.Its pathogenesis is not fully understood,and early diagnosis is challenging owing to the lack of effective biomarkers.This study aimed to analyze different samples to identify potential biomarkers and therapeutic targets.Methods::Microarray datasets of RA,osteoarthritis(OA),and healthy control(HC)were downloaded from the Gene Expression Omnibus database.R software was used to identify differentially expressed genes(DEGs),which were visualized using volcano and heat maps.Venn diagrams,principal component analysis,gene set enrichment analysis,gene ontology,and Kyoto Encyclopedia of genes and genomes were used to analyze the data.A protein–protein interaction network was constructed,and synovial tissues from patients with RA and OA were collected for verification using the collagen-induced arthritis mouse model.Results::More DEGs were found in synovial tissues than in peripheral blood mononuclear cells or fibroblast-like synoviocytes.Principal component analysis revealed significant differences between the RA and OA samples,highlighting the unique advantages of synovial tissue.Enrichment analysis revealed that metabolic and cytokine signaling pathways play crucial roles in the development of RA.Further analysis of the four synovial datasets identified 54 DEGs,of which signaling lymphocytic activation molecule family(SLAMF)8 was identified as the key molecule.SLAMF8 levels were increased in the synovial tissue of patients with RA compared to those of patients with OA(0.38±0.19 vs.12.40±1.66),and SLAMF8 levels were similarly elevated in collagen-induced arthritis model mice compared with those in the healthy mice(1.13±0.47 vs.9.05±2.52).Conclusions::This study established the unique advantages of synovial tissue for RA research and identified metabolic and cytokine signaling pathways as important for RA development.Thus,SLAMF8 may be a potential therapeutic target for RA.

REGULAR EXPRESSION OF DISCOIDIN DOMAIN RECEPTOR 2 IN THE IMPROVED ADJUVANT-INDUCED ANIMAL MODEL FOR RHEUMATOID ARTHRITIS

Objective To investigate the expression of discoidin domain receptor 2 (DDR2) of fibroblast-like synovial cells in im- proved adjuvant-induced animal (AIA) model for rheumatoid arthritis (RA) and to provide evidence for DDR2’s antagonist use clinically. Methods AIA was modified by administrating 0.1 mL of complete Freund’s adjuvant (CFA, mixed with 5 mg Bacillus Calmette-Guerin vaccine/mL) into rats’ right hind paws and 0.125 mL tumor necrosis factor-α (2 U/mL) into right ankles and subpatellar fatty tissue. The expression of DDR2 in fibroblast-like synovial cells was assessed using immunohistochemistry, immunofluorescence histochemistry, and in situ hybridization methods. Levels of anti-collagen II antibody were measured using enzyme-linked immunosorbent assay. Results Given the terms mentioned above, we found a more practical rat model, apparently decreasing immunization time (average 3-5 days). DDR2 can be detected upon the 15th day of immunization; expression gradually increased with time going on, and reaching a peak 35 days after immunization before gradually decreasing. Serum anti-collagen II antibody showed similar expression patterns as DDR2, but reached peak later than DDR2, about 40 days after immunization. Conclusion Regular expression of DDR2 in animal models infers its important role in the pathological process of RA.