[1]朱玉光,方丽佳,黄素玲.类风湿关节炎患者关节滑液及滑膜组织中CCP/AST表达水平及临床意义[J].现代检验医学杂志,2024,39(01):162-165+174.[doi:10.3969/j.issn.1671-7414.2024.01.030]
 ZHU Yuguang,FANG Lijia,HUANG Suling.Expression Level of CCP/AST in Synovial Fluid and Synovial Tissue of Rheumatoid Arthritis Patients and Its Clinical Significance[J].Journal of Modern Laboratory Medicine,2024,39(01):162-165+174.[doi:10.3969/j.issn.1671-7414.2024.01.030]
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类风湿关节炎患者关节滑液及滑膜组织中CCP/AST表达水平及临床意义()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年01期
页码:
162-165+174
栏目:
检验与临床
出版日期:
2024-01-15

文章信息/Info

Title:
Expression Level of CCP/AST in Synovial Fluid and Synovial Tissue of Rheumatoid Arthritis Patients and Its Clinical Significance
文章编号:
1671-7414(2024)01-162-05
作者:
朱玉光方丽佳黄素玲
(石家庄市中医院检验科,石家庄 050011)
Author(s):
ZHU Yuguang FANG Lijia HUANG Suling
(Department of Clinical Laboratory, Shijiazhuang Hospital of Traditional Chinese Medicine, Shijiazhuang 050011, China)
关键词:
类风湿关节炎关节滑液滑膜组织环瓜氨酸肽抗原特异性T 细胞
分类号:
R512.91
DOI:
10.3969/j.issn.1671-7414.2024.01.030
文献标志码:
A
摘要:
目的 探究类风湿关节炎(rheumatoid arthritis,RA)患者关节滑液及滑膜组织中环瓜氨酸肽抗原特异性T细胞(cyclic citrullinated peptide antigen-specific T cells,CCP/AST)表达水平及临床意义。方法 选取石家庄市中医院2021 年1 月~12 月128 例RA 患者为RA 组,并取同期在该院因关节疼痛需做关节镜检查者50 例为对照组。其中RA 患者轻度组46 例,中度组52 例和重度组30 例;通过蛋白印迹分析各组受试者滑膜组织类风湿因子(rheumatoidfactors, RF)和抗瓜氨酸蛋白抗体(anticitrullinated protein antibodies, ACPA)蛋白表达水平;通过流式细胞仪分析受试者关节滑液中CCP/AST 频率;双重免疫荧光染色/ 激光共聚焦扫描观察滑膜组织中CCP/AST 染色强度;Pearson 相关性分析评估关节滑液、滑膜组织中CCP/AST 表达与RF 和ACPA 的相关性;采用Logistic 回归分析RA 发生的危险因素。结果 对照组、轻度组、中度组和重度组患者滑膜组织中RF(1.01 ± 0.01,1.53 ± 0.03,2.01 ± 0.08,2.66 ± 0.12kDa)和ACPA蛋白(1.03 ± 0.01,1.61 ± 0.03,2.04 ± 0.10,2.59 ± 0.13 kDa)依次升高,差异具有统计学意义(F=14.207,12.446,均P<0.05)。对照组、轻度组、中度组和重度组患者关节滑液中CCP/AST 表达依次升高(8.26% ± 1.68%,22.46% ± 3.28%,33.58% ± 4.37%,46.15% ± 5.44%),差异具有统计学意义(F=25.306,P<0.05)。对照组、轻度组、中度组和重度组患者滑膜组织CCP/AST 染色强度依次升高(1.05 ± 0.26,1.35 ± 0.89,2.04 ± 0.56,2.78 ± 0.15分),差异具有统计学意义(F=70.67,P<0.05)。RA 患者关节滑液、滑膜组织中CCP/AST 表达与RF 呈明显正相关(r=0.861,0.934,均P<0.05),与ACPA 呈明显正相关(r=0.854,0.913,均P<0.05)。Logistic 回归分析结果显示,高血压(OR=3.241,95%CI:1.491 ~ 6.752)、糖尿病(OR=2.565,95%CI:1.126 ~ 5.813)以及关节滑液(OR=4.450,95%CI:1.652 ~ 11.622)、滑膜组织(OR=5.629,95%CI:2.474 ~ 12.390)中CCP/AST 表达均为RA 发生的独立危险因素(P<0.05)。结论 RA 患者关节滑液及滑膜组织中CCP/AST 呈现高表达,且与疾病活动度及关节破坏有关,可用于评估此类患者临床关节活动度及骨破坏程度。
Abstract:
Objective To investigate the expression level and clinical significance of cyclic citrullinated peptide antigen-specific T cells (CCP/AST) in synovial fluid and synovial tissue of rheumatoid arthritis (RA) patients. Methods A total of 128 RA patients in Shijiazhuang Hospital of Traditional Chinese Medicine from January to December 2021 were selected as the RA group, and 50 patients who needed arthroscopy for joint pain in the hospital during the same period were selected as the control group. Among the RA group, there were 46 cases in the mild group, 52 cases in the moderate group, and 30 cases in the severe group. The protein expression levels of rheumatoid factors(RF) and anticitrullinated protein antibodies(ACPA) in synovial tissues of the subjects in each group were analyzed by Western blot. The frequency of CCP/AST in the synovial fluid of the subjects was analyzed by flow cytometry. The intensity of the staining of CCP/AST in synovial tissues was observed by double immunofluorescence staining/laser confocal scanning. Pearson correlation analysis was used to assess the correlation between the CCP/AST expression of synovial fluid and synovial tissue and RF and ACPA. Logistic regression was used to analyze the risk factors for the development of rheumatoid arthritis. Results In the order of control, mild, moderate and severe groups, RF (1.01 ± 0.01, 1.53 ± 0.03, 2.01 ± 0.08, 2.66 ± 0.12 kDa) and ACPA proteins (1.03 ± 0.01, 1.61 ± 0.03, 2.04 ± 0.10, 2.59 ± 0.13 kDa) in synovial tissues of patients were sequentially elevated, and the differences were all statistically significant (F=14.207,12.446, all P<0.05). The expression of CCP/AST in synovial fluid of patients in the control, mild, moderate and severe groups was increased sequentially (8.26% ± 1.68%, 22.46% ± 3.28%, 33.58% ± 4.37%, 46.15% ± 5.44%), and the difference was statistically significant (F=25.306, P<0.05). Meanwhile, the intensity of CCP/AST staining in synovial tissues of patients in the control, mild, moderate and severe groups was also increased sequentially (1.05 ± 0.26, 1.35 ± 0.89, 2.04 ± 0.56, 2.78 ± 0.15 score), and the difference was statistically significant (F=70.67, P<0.05). The expression of CCP/AST in the synovial fluid and synovial tissues of patients with RA was positively correlated with RF (r=0.861, 0.934, all P< 0.05) and ACPA in synovial fluid and synovial tissue (r=0.854, 0.913, all P< 0.05). Logistic regression analysis showed that hypertension (OR=3.241, 95%CI: 1.491~6.752), diabetes mellitus (OR=2.565, 95%CI:1.126 ~ 5.813), synovial fluid (OR=4.450, 95%CI:1.652 ~ 11.622), and CCP/AST expression in synovial tissues (OR=5.629, 95%CI:2.474 ~ 12.390) were independent risk factors for the development of RA (P< 0.05). Conclusion CCP/AST showed high expression in synovial fluid and synovial tissue of RA patients and related to disease activity and joint destruction, which can be used to assess the clinical joint mobility and bone destruction degree in such patients.

参考文献/References:

[1] 陈建芸, 廖海平, 孙朝晖, 等.类风湿性关节炎患者血清RA-CP, 抗CCP 抗体及RF 检测对RA 的实验诊断意义[J]. 现代检验医学杂志, 2020, 35(5): 38-40, 50. CHEN Jianyun, LIAO Haiping, SUN Chaohui, et al. Significance of the detection of RA-CP, anti-CCP antibody and RF in the laboratory diagnosis of rheumatoid arthritis[J]. Journal of Modern Laboratory Medicine, 2020, 35(5): 38-40, 50.
[2] 陈龙梅, 杨振华.基于GEO 数据库对类风湿性关节炎相关基因筛选及生物信息学分析[J].现代检验医学杂志, 2021, 36(2): 49-52, 78. CHEN Longmei, YANG Zhenhua. Gene screening and bioinformatics analysis of rheumatoid arthritis based on GEO database[J]. Journal of Modern Laboratory Medicine, 2021, 36(2): 49-52, 78.
[3] 李正芳, 罗采南, 武丽君, 等.抗瓜氨酸化α 烯醇化酶多肽1 抗体在类风湿关节炎中的研究进展[J].中华医学杂志, 2020, 100(2): 158-160. LI Zhengfang, LUO Cainan, WU Lijun, et al. Research progress of anti-citcitinated α-enolase polypeptide 1 antibody in rheumatoid arthritis[J]. National Medical Journal of China, 2020, 100(2): 158-160.
[4] GERLAG D M, SAFY M, MAIJER K I, et al. Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study[J]. Annals of the Rheumatic Diseases, 2019, 78(2): 179-185.
[5] MEKIC M, HADZIGRAHIC E. Anti-cyclic citrullinated peptide antibody as a predictor of rheumathoid arthritis complications[J]. Medical Archives, 2020, 74(3): 183-186.
[6] EBRAHIMI-RAD M, KHATAMI S, AKHBARI H, et al. Evaluation of autoantibodies against vimentin and α-enolase in rheumatoid arthritis patients[J].Reumatologia, 2020, 58(6): 350-356.
[7] ZHOU Jiansuo, FENG Limei, ZHANG Hua, et al. Evaluation of the value of anti-citrullinated α-enolase peptide 1 antibody in the diagnosis of rheumatoid arthritis[J]. Annals of Clinical and Laboratory Science, 2019, 49(4): 503-506.
[8] 吴瑞荷, 丁婷婷, 薛宏伟, 等.辅助性T 细胞9/白细胞介素-9 调控类风湿关节炎中辅助性T 细胞17/调节性T 细胞免疫平衡的研究进展[J]. 中华风湿病学杂志, 2020, 24(3): 206-209. WU Ruihe, DING Tingting, XUE Hongwei, et al. Research progress of helper T cell 9/interleukin-9 regulating helper T cell 17/regulatory T cell immune balance in rheumatoid arthritis[J]. Chinese Journal of Rheumatology, 2020, 24(3): 206-209.
[9] ENGLAND B R, TIONG B K, BERGMAN M J, et al. 2019 update of the American college of rheumatology recommended rheumatoid arthritis disease activity measures[J]. Arthritis Care & Research, 2019, 71(12): 1540-1555.
[10] LIU Yudong, LIU Chenxi, LI Liubing, et al. High levels of antibodies to citrullinated α-enolase peptide-1 (CEP-1) identify erosions and interstitial lung disease (ILD) in a Chinese rheumatoid arthritis cohort[J].Clinical Immunology, 2019, 200: 10-15.
[11] YOSHIZAWA Y, NAKAO T, TSURITANI K, et al. The importance of specific citrullinated clusterin and vimentin found in a multi-coloured beadbased citrulline-peptide array system in rheumatoid arthritis[J]. Clinical and Experimental Rheumatology, 2022, 40(5): 936-944.
[12] R?NNELID J, TURESSON C,KASTBOM A. Autoantibodies in rheumatoid arthritis-laboratory and clinical perspectives[J]. Frontiers in Immunology, 2021, 14(12): 685312.
[13] PETROVSK? N, PRAJZLEROV? K, VENCOVSK? J, et al. The pre-clinical phase of rheumatoid arthritis: from risk factors to prevention of arthritis[J].Autoimmunity Reviews, 2021, 20(5): 102797.
[14] WU Chaoyi, YANG Huangyu, LUO Shuefen, et al. From rheumatoid factor to anti-citrullinated protein antibodies and anti-carbamylated protein antibodies for diagnosis and prognosis prediction in patients with rheumatoid arthritis[J]. International Journal of Molecular Sciences, 2021, 22(2): 686.
[15] KHATRI S, HANSEN J, PEDERSEN N B, et al. Cyclic citrullinated peptide aptamer treatment attenuates collagen-induced arthritis[J]. Biomacromolecules, 2022, 23(5): 2126-2137.
[16] YANG C A, LI Jupi, LAI Yihua, et al. Assessing the immune cell subset and genetic mutations in patients with palindromic rheumatism seronegative for rheumatoid factor and anti-cyclic citrullinated peptide[J]. Arthritis & Rheumatology, 2023, 75(2): 187-200.
[17] DEMORUELLE M K. Improving the prediction of rheumatoid arthritis using multiple anticyclic citrullinated peptide assays[J]. Arthritis & Rheumatology, 2020, 72(11): 1789-1790.
[18] 杨宝琦, 马丹, 武泽文, 等.T 细胞代谢在类风湿关节炎发病机制中的作用研究进展[J]. 中华风湿病学杂志, 2021, 25(10): 691-695. YANG Baoqi, MA Dan, WU Zewen, et al. Research progress on mechanism of T cell metabolism in the pathogenesis of rheumatoid arthritis[J]. Chinese Journal of Rheumatology, 2021, 25(10): 691-695.
[19] IYENGAR K P, VAISH A, NUNE A. Anti-cyclic citrullinated peptide antibody (ACPA) and rheumatoid arthritis: clinical relevance[J]. Journal of Clinical Orthopaedics and Trauma, 2022, 24: 101729.

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备注/Memo

备注/Memo:
基金项目:河北省卫生健康委2022 年度医学科学研究课题计划项目(编号:20221722):ENO1 对类风湿病小鼠免疫功能的双重作用。
作者简介:朱玉光(1980-),男,本科,主管检验师,主要从事医学检验工作,E-mail:qingchuang218@163.com。
更新日期/Last Update: 2024-01-15