Identification of citrullinated α1-antitrypsin (A1AT) in saliva in a mouse model of rheumatoid arthritis

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Journal of Oral Biosciences Pub Date : 2024-06-01 DOI:10.1016/j.job.2024.03.007
Wakako Sakaguchi , Juri Saruta , Yuko Yamamoto , Tomoko Shimizu , Shinya Fuchida , Keiichi Tsukinoki
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Abstract

Objectives

Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive joint destruction. Early diagnosis and treatment, before joint deformation or destruction occurs, are crucial. Identifying novel biomarkers for RA in saliva could potentially enable early detection of the disease, prior to its onset.

Methods

We conducted a comprehensive proteomic analysis of salivary proteins in a mouse model of RA. Proteins were identified using western blotting and enzyme-linked immunosorbent assay in the serum, saliva, and ankle joints of DBA/1JJmsSlc mice, a model of RA. Ankle joints and submandibular glands were stained with hematoxylin and eosin and immunostained, and the results were compared with those of control mice.

Results

Citrullinated alpha-1 antitrypsin (A1AT, 46 kDa) was commonly detected in the saliva, serum, and ankle joints of mice with severe RA and was confirmed through proteomic analysis. Western blotting showed a band corresponding to 46 kDa in the serum, saliva, and ankle joints. Immunostaining of the ankle joints with the A1AT antibody showed a strong positive signal in the synovium.

Conclusions

In DBA/1JJmsSlc mice, cyclic citrullinated peptide antibodies and A1AT may be involved in citrullination and contribute to the development and severity of RA, making them valuable treatment targets requiring further study.

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鉴定类风湿性关节炎小鼠模型唾液中的瓜氨酸化α1-抗胰蛋白酶(A1AT)。
目的:类风湿性关节炎(RA)是一种以进行性关节破坏为特征的自身免疫性疾病。在关节变形或破坏发生之前进行早期诊断和治疗至关重要。鉴定唾液中的新型类风湿性关节炎生物标志物有可能在疾病发作前对其进行早期检测:我们对RA小鼠模型的唾液蛋白质进行了全面的蛋白质组学分析。我们使用 Western 印迹法和酶联免疫吸附法鉴定了 DBA/1JJmsSlc 小鼠(一种 RA 模型)血清、唾液和踝关节中的蛋白质。对踝关节和颌下腺进行苏木精和伊红染色及免疫染色,并将结果与对照组小鼠进行比较:结果:在严重RA小鼠的唾液、血清和踝关节中普遍检测到瓜氨酸化α-1抗胰蛋白酶(A1AT,46 kDa),并通过蛋白质组分析得到证实。Western 印迹显示,在血清、唾液和踝关节中都有一条与 46 kDa 相对应的条带。用 A1AT 抗体对踝关节进行免疫染色显示,滑膜中出现了强烈的阳性信号:结论:在DBA/1JJmsSlc小鼠中,环瓜氨酸肽抗体和A1AT可能参与瓜氨酸化,并导致RA的发生和严重程度,因此是有价值的治疗靶点,需要进一步研究。
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来源期刊
Journal of Oral Biosciences
Journal of Oral Biosciences DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
4.40
自引率
12.50%
发文量
57
审稿时长
37 days
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