类风湿关节炎患者趋化因子CXCL9和CXCL10在骨侵蚀中的作用

doi:10.19723/j.issn.1671-167X.2021.06.003

摘要/Abstract

摘要：

目的:检测趋化因子CXCL9和CXCL10在类风湿关节炎(rheumatoid arthritis, RA)患者外周血中的水平,分析其对RA发生骨侵蚀的作用,探讨CXCL9和CXCL10在RA中的临床意义。方法:采用酶联免疫吸附试验(enzyme linked immunosorbent assay, ELISA)检测105例RA患者、90例骨关节炎(osteoarthritis, OA)患者和25例健康对照者(healthy control, HC)血清CXCL9、CXCL10水平并比较各组间差异,分析其与RA临床特征、实验室指标、疾病活动性及骨侵蚀的相关性,采用Logistic回归分析血清CXCL9和CXCL10水平与RA患者骨侵蚀的相关性。结果:RA组患者血清CXCL9、CXCL10水平显著高于OA组和HC组(P<0.01、P<0.01),RA患者血清CXCL9水平与肿胀关节数(swollen joints, SJC)、类风湿因子(rheumatoid factor, RF)呈正相关(P<0.05),血清CXCL10水平与压痛关节数(tender joints, TJC)、SJC、C反应蛋白(C-reactive protein, CRP)、免疫球蛋白(immunoglobulin, Ig)A、IgM、RF及抗环瓜氨酸多肽抗体(anti-cyclic citrullinated peptide antibody,ACPA)呈正相关(P<0.05)。此外,血清CXCL9、CXCL10水平均与RA疾病活动度评分(disease activity score 28, DAS28)呈正相关(P=0.013、P=0.006),且高疾病活动度组(DAS28≥5.1)的血清CXCL9、CXCL10水平显著高于中低疾病活动度组(DAS28<5.1,P<0.05)。Logistic回归分析提示,病程长、高疾病活动度及血清CXCL9水平升高与RA患者发生骨侵蚀相关(P<0.05)。结论:RA患者血清趋化因子CXCL9和CXCL10的表达水平升高,与RA疾病活动性及骨侵蚀具有相关性,可能参与了RA的发病及骨破坏过程。

关键词: 类风湿关节炎, 骨侵蚀, 趋化因子CXCL9, 趋化因子CXCL10

Abstract:

Objective: To detect the serum level of soluble chemokines CXCL9 and CXCL10 in patients with rheumatoid arthritis (RA), and to analyze their correlation with bone erosion, as well as the clinical significance in RA. Methods: In the study, 105 cases of RA patients, 90 osteoarthritis (OA) patients and 25 healthy controls in Peking University People’s Hospital were included. All the clinical information of the patients was collected, and the serum CXCL9 and CXCL10 levels of both patients and healthy controls were measured by enzyme-linked immune sorbent assay (ELISA). CXCL9 and CXCL10 levels among different groups were compared. The correlation between serum levels with clinical/laboratory parameters and the occurrence of bone erosion in RA were analyzed. Independent sample t test, Chi square test, Mann-Whitney U test, Spearman’s rank correlation and Logistic regression were used for statistical analysis. Results: The levels of CXCL9 and CXCL10 were significantly higher in the RA patients [250.02 (126.98, 484.29) ng/L, 108.43 (55.16, 197.17) ng/L] than in the OA patients [165.05 (75.89, 266.37) ng/L, 69.00 (33.25, 104.74) ng/L] and the health controls [79.47 (38.22, 140.63) ng/L, 55.44 (18.76, 95.86) ng/L] (all P<0.01). Spearman’s correlation analysis showed that the level of serum CXCL9 was positively correlated with swollen joints (SJC), rheumatoid factor (RF) and disease activity score 28 (DAS28) (r=0.302, 0.285, 0.289; P=0.009, 0.015, 0.013). The level of serum CXCL10 was positively correlated with tender joints (TJC), SJC, C-reactive protein (CRP), immunoglobulin (Ig) A, IgM, RF, anti-cyclic citrullinated peptide antibody (ACPA), and DAS28 (r=0.339, 0.402, 0.269, 0.266, 0.345, 0.570, 0.540, 0.364; P=0.010, 0.002, 0.043, 0.045, 0.009, <0.001, <0.001, 0.006). Serum CXCL9 and CXCL10 levels in the RA patients with bone erosion were extremely higher than those without bone erosion [306.84 (234.02, 460.55) ng/L vs. 149.90 (75.88, 257.72) ng/L, 153.74 (89.50, 209.59) ng/L vs. 54.53 (26.30, 83.69) ng/L, respectively] (all P<0.01). Logistic regression analysis showed that disease duration, DAS28 and serum level of CXCL9 were correlated with bone erosion in the RA patients (P<0.05). Conclusion: Serum levels of CXCL9 and CXCL10 were remarkably elevated in patients with RA, and correlated with disease activities and occurrence of bone erosion. Chemokines CXCL9 and CXCL10 might be involved in the pathogenesis and bone destruction in RA.

Key words: Rheumatoid arthritis, Bone erosion, Chemokine CXCL9, Chemokine CXCL10

中图分类号:

R593.22

钟华,徐丽玲,白明欣,苏茵. 类风湿关节炎患者趋化因子CXCL9和CXCL10在骨侵蚀中的作用[J]. 北京大学学报（医学版）, 2021, 53(6): 1026-1031.

ZHONG Hua,XU Li-ling,BAI Ming-xin,SU Yin. Effect of chemokines CXCL9 and CXCL10 on bone erosion in patients with rheumatoid arthritis[J]. Journal of Peking University (Health Sciences), 2021, 53(6): 1026-1031.

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参考文献 23

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Items	All subjects	Without bone erosion	With bone erosion	P value
Patients, n	52	17	35
Gender, n
Female	38	12	26	0.778
Male	14	5	9
Age/years	56 (52, 66)	55 (51, 66)	57 (52, 70)	0.667
Disease duration/month	60 (21, 204)	36 (8, 66)	84 (24, 240)	0.010
SJC, n	4 (1, 8)	2 (0, 8)	5 (2, 8)	0.234
TJC, n	4 (1, 8)	5 (2, 8)	2 (1, 7)	0.169
ESR/(mm/h)	52 (24, 100)	33 (13, 88)	61 (36, 102)	0.077
CRP/(mg/L)	21.30 (6.42, 53.25)	11.40 (3.07, 48.95)	30.90 (9.10, 53.80)	0.084
IgA/(g/L)	2.43 (1.75, 3.59)	2.01 (1.69, 2.86)	2.59 (1.80, 3.81)	0.172
IgG/(g/L)	11.95 (10.43, 13.30)	10.70 (9.77, 12.80)	12.40 (10.70, 14.30)	0.141
IgM/(g/L)	1.29 (0.82, 1.78)	1.22 (0.73, 1.51)	1.34 (0.92, 1.93)	0.310
RF/(IU/mL)	136.50 (31.28, 340.25)	133.00 (34.15, 404.50)	138.00 (28.00, 353.00)	0.984
ACPA/(U/mL)	144.57 (23.91, 200.00)	118.02 (63.96, 200.00)	155.81 (8.36, 200.00)	0.579
DAS28	4.74±1.26	4.52±1.35	4.85±1.22	0.385
CXCL9/(ng/L)	280.27 (150.50, 439.83)	149.90 (75.88, 257.72)	306.84 (234.02, 460.55)	<0.001
CXCL10/(ng/L)	107.10 (52.62, 200.33)	54.43 (26.30, 83.69)	153.74 (89.50, 209.59)	0.001

Items	β	Wald	OR	95%CI	P value
Disease duration	0.015	6.550	1.015	1.003-1.026	0.010
ACPA	-0.005	0.834	0.995	0.985-1.006	0.361
DAS28	1.063	4.539	2.896	1.089-7.701	0.033
CXCL9	0.011	8.339	1.012	1.004-1.019	0.004
CXCL10	-0.004	3.204	0.996	0.992-1.000	0.073