Lumican蛋白在类风湿关节炎患者血清中的表达及其与疾病和免疫活动的相关性

doi:10.19723/j.issn.1671-167X.2025.05.015

摘要/Abstract

摘要： 目的: 探讨基膜聚糖(lumican, LUM)蛋白在类风湿关节炎(rheumatoid arthritis, RA)患者血清中的表达水平及其与RA疾病及免疫活动的相关性。方法: 采用酶联免疫吸附法检测RA患者和健康对照者血清LUM水平，收集患者临床及实验室资料，对比不同特征RA患者血清LUM的表达差异，分析血清LUM水平与临床及实验室指标间的相关性。数据分析分别采用独立样本t检验、Spearman相关分析、方差分析及LSD-t检验、K-W检验及Bonferroni检验、卡方检验，P＜0.05为差异有统计学意义。结果: RA患者血清LUM水平显著高于健康对照者(P＜0.000 1)。LUM与红细胞沉降率(erythrocyte sedimentation rate, ESR)、C反应蛋白(C-reactive protein, CRP)、类风湿因子(rheumatoid factor, RF)、免疫球蛋白A(immunoglobulin A, IgA)、血小板计数和28个关节的疾病活动度评分(28-joint disease activity score，DAS28)相关(P＜0.05)。不同病程及性别的RA患者血清LUM差异无统计学意义(P>0.05)，RF阳性的RA患者血清LUM显著高于RF阴性的RA患者和健康对照者(P＜0.05)，不同ESR、CRP水平的RA患者血清LUM水平均显著高于健康对照者(P＜0.05)，疾病处于缓解期的RA患者血清LUM水平显著低于疾病处于中、高度活动度的RA患者(P＜0.05)，RF阳性的RA患者血清LUM阳性率显著高于RF阴性的患者(P＜0.05)。结论: LUM蛋白有可能成为一个反映RA疾病活动度及免疫活动度的生物标记物。

关键词: 基膜聚糖, 类风湿关节炎, 类风湿因子, 抗瓜氨酸化蛋白抗体

Abstract: Objective: To investigate the serum level of lumican (LUM) and its clinical correlation with disease and immune activities in patients with rheumatoid arthritis (RA). Methods: The serum LUM levels in both RA patients and health controls (HCs) were detected by enzyme-linked immunosorbent assay (ELISA). The clinical and laboratory data of the patients were collected. The LUM levels in the patients with different clinical features were analyzed. The correlation between the clinical data, laboratory parameters, and serum LUM levels were also analyzed. Independent samples t test, Spearman correlation were used for statistical analysis. Analysis of variance and Kruskal-Wallis test, the least significant difference (LSD)-t test and Bonferroni correction were used for statistical analysis. The Pearson Chi-square test was used for comparison of the rates between the groups. Statistical significance was set at P < 0.05. Results: The levels of LUM were elevated in the RA patients than in the HCs (P < 0.000 1). Serum LUM levels were correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A (IgA), titers of platelet (PLT) and 28-joint disease activity score (DAS28, all P < 0.05). Next, we compared the serum LUM levels in the RA patients with different characteristics, and no difference was found in serum LUM levels between early-RA and RA, the same to RA with different gender (P>0.05). The levels of serum LUM were elevated in the RF positive patients (P < 0.000 1), and in the RF and anti-CCP positive patients (P < 0.05) than in the RA patients with negative RF whether the anti-CCP was positive. In addition, no differences were found between the RA patients with negative RF whether the anti-CCP was positive (P>0.05). All the levels of serum LUM were elevated in the RA patients with different CRP or ESR than in the HCs (P < 0.05), and the serum LUM levels in the RA patients with elevated ESR and CRP were significantly elevated in those with normal ESR and CRP (P < 0.05). Additionally, the results demonstrated that serum LUM levels were positively associated with RA disease activity, and they were declined in RA sustained remission than those in middle or high disease activity (P < 0.05). Furthermore, no difference was found between the RA patients in remission and HCs (P>0.05). No differences were found in the RA patients with and without complications including interstitial pneumonia disease, Sjögren's syndrome, thyroid gland diseases and osteoporosis (P>0.05). The LUM positivity rates were significantly elevated in the RF positive patients than the RF negative patients in RA (P < 0.05). Conclusion: LUM, a cyclocitrullinated protein, might be a promising biomarker which could reflect both disease activity and immune activity in RA.

Key words: Lumican, Rheumatoid arthritis, Rheumatoid factor, Anti-citrullinated protein antibodies

中图分类号:

R593.22

杨菊, 徐婧, 戴菊华, 石连杰. Lumican蛋白在类风湿关节炎患者血清中的表达及其与疾病和免疫活动的相关性[J]. 北京大学学报（医学版）, 2025, 57(5): 911-918.

Ju YANG, Jing XU, Juhua DAI, Lianjie SHI. Expression of lumican protein in serum of patients with rheumatoid arthritis and its correlation with disease and immune activities[J]. Journal of Peking University (Health Sciences), 2025, 57(5): 911-918.

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Characteristics	Data
RA (n=133)
Seropositive	115 (86.5)
Seronegative	18 (13.5)
Gender (n=133)
Male	32 (24.1)
Female	101 (75.9)
Age/years	58.26±14.31
Laboratory features
ESR/(mm/h) (n=124)	36.00 (13.25, 73.00)
CRP/(mg/L) (n=131)	12.52 (2.80, 50.29)
RF/(IU/mL) (n=133)	86.60 (23.05, 280.00)
Anti-CCP/(U/mL) (n=126)	234.95 (73.58, 444.73)
IgA/(g/L) (n=105)	2.83 (1.97, 3.90)
IgM/(g/L) (n=105)	1.26 (0.91, 1.59)
IgG/(g/L) (n=105)	13.73 (11.36, 17.00)
C3/(g/L) (n=104)	1.22±0.31
C4/(g/L) (n=104)	0.20 (0.16, 0.26)
PLT/(×10⁹/L) (n=125)	268 (203, 339)
RA activity (score according to DAS28-CRP) (n=133)^*
HDA (n=64)	23.66±5.13
MDA (n=35)	22.37±5.13
LDA (n=8)	21.92±6.15
Remission (n=20)	18.88±5.19
Complications (n=133)
ILD	16 (12.0)
SS	10 (7.5)
TGD	38 (28.6)
OP	50 (37.6)
LUM/(μg/L) (n=133)	22.17±5.47

Characteristics	Serum LUM levels
Characteristics	R	P
Age	0.132	0.130
Disease duration	0.032	0.715
ESR	0.295	0.001^**
CRP	0.229	0.008^**
RF	0.366	＜0.001^***
Anti-CCP	0.129	0.150
IgA	0.227	0.020^**
IgM	0.163	0.097
IgG	0.170	0.082
C3	0.128	0.195
C4	-0.147	0.136
PLT	0.299	0.001^**
DAS28-CRP	0.274	0.002^**

Group	RA with LUM, n (%)	RA without LUM, n (%)	χ² value	P value
RF+	63 (60.0)	42 (40.0)	8.774	0.003
RF-	8 (28.6)	20 (71.4)
Anti-CCP+	64 (59.8)	43 (40.2)	3.461	0.063
Anti-CCP-	7 (36.8)	12 (63.2)