Chinese Journal of Tissue Engineering Research ›› 2024, Vol. 28 ›› Issue (35): 5606-5611.doi: 10.12307/2024.574

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Osteoclast differentiation induced by total immune complex in serum of patients with rheumatoid arthritis leads to osteoporosis and its factors analysis

Zhou Erye, Zeng Keqin, Wu Jian, Ren Tian, He Michun   

  1. Department of Rheumatology, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
  • Received:2023-09-21 Accepted:2023-12-02 Online:2024-12-18 Published:2024-03-15
  • Contact: Zeng Keqin, MD, Chief physician, Department of Rheumatology, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
  • About author:Zhou Erye, Master, Associate chief physician, Department of Rheumatology, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
  • Supported by:
    the National Natural Science Foundation of China, No. 81771782 (to WJ); Suzhou Minsheng Science and Technology Project, No. SYSD2020103 (to ZKQ)

Abstract: BACKGROUND: The incidence of osteoporosis significantly increases in the patients with rheumatoid arthritis, and it remains unclear whether the presence of a large number of immune complexes in serum promotes the onset and development of osteoporosis. 
OBJECTIVE: To investigate the correlation between serum immune complexes and osteoporosis in patients with rheumatoid arthritis. 
METHODS: (1) Clinical trial: Serum and clinical data of 50 healthy controls and 50 patients with untreated rheumatoid arthritis were collected and retrospectively analyzed. Total immune complex level in serum was compared between two groups. Correlation of serum total immune complexes with bone mineral density, bone turnover markers and other clinical indicators in patients with rheumatoid arthritis was analyzed. (2) Cell experiment: Peripheral blood mononuclear cells from healthy volunteers were isolated and cultured, and divided into four groups: rheumatoid arthritis group was added with total immune complex suspension from rheumatoid arthritis patients; normal control group was added with total immune complex suspension from healthy medical checkups; positive control group was added with α-MEM medium containing macrophage colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand, and negative control group was added with α-MEM medium. Tartrate-resistant acid phosphatase staining was performed to observe the formation of osteoclasts after 7 days of treatment, 
RESULTS AND CONCLUSION: (1) Clinical trial: The total immune complex and serum alkaline phosphatase levels in patients with rheumatoid arthritis were significantly higher than those in health controls (P < 0.01, P < 0.05). Pearson correlation analysis showed that serum total immune complex level was positively correlated with erythrocyte sedimentation rate (r=0.330, P=0.019), serum alkaline phosphatase (r=0.545, P=0.001), anti-cyclic citrullinate peptide (r=0.377, P=0.007) and c-terminal telopeptide of type I collagen (r=0.738, P=0.001), and negatively correlated with lumbar bone mineral density (r=-0.595, P=0.001) in patients with rheumatoid arthritis. Binary Logistic regression analysis showed that age [odds ratio (OR)=1.086, 95% confidence interval (CI) (1.022,1.154), P=0.008], anti-cyclic citrullinate peptide [OR=1.002, 95% CI (0.999,1.005), P=0.035], c-terminal telopeptide of type I collagen [OR=0.141, 95% CI (0.015, 8.900), P=0.008] and serum total immune complexes [OR=2.895, 95% CI (1.228, 6.827), P=0.001] were the influencing factors for abnormal bone mass (reduced bone mass or osteoporosis) in patients with rheumatoid arthritis. (2) Cell experiment: Tartrate-resistant acid phosphatase positive osteoclasts were observed in the positive control group, normal control group and rheumatoid arthritis group, and there were more osteoclasts in the rheumatoid arthritis group than in the normal control group (P < 0.01). To conclude, serum total immune complexes can be used as a potential serologic predictor of rheumatoid arthritis complicated with osteoporosis, and removing immune complexes in serum or interfering with the binding of immune complexes to their receptors may be an effective means for the prevention and treatment of rheumatoid arthritis complicated with osteoporosis.

Key words: rheumatoid arthritis, immune complex, bone turnover marker, osteoporosis, osteoimmunology

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