抗氨基甲酰化蛋白抗体在诊断类风湿关节炎中的应用价值

doi:10.19723/j.issn.1671-167X.2024.04.029

摘要/Abstract

摘要：

目的: 探讨抗氨基甲酰化蛋白(carbamylated protein，CarP)抗体在类风湿关节炎(rheumatoid arthritis，RA)中的表达水平及应用价值。方法: 回顾2018年12月至2019年6月就诊于新疆维吾尔自治区人民医院风湿免疫科的RA患者、非RA患者以及体检中心健康对照人群的人口学资料、实验室检查结果及肌肉骨骼超声结果，采用间接酶联免疫吸附试验测定各研究对象血清中抗CarP抗体的浓度并进行统计学分析。结果: 共纳入259例研究对象，其中RA组158例(包括血清阴性RA 45例)，非RA组59例，健康对照组42例。RA组患者抗CarP抗体浓度[8.31(5.22，15.26) U/mL]高于非RA组[4.50(3.35，5.89) U/mL]及健康对照组[3.46(2.76，4.92) U/mL]；非RA组抗CarP抗体浓度与健康对照组相比，差异无统计学意义(P=0.10)。受试者工作特征(receiver operating characteristic，ROC)曲线分析抗CarP抗体诊断RA的灵敏度58.2%、特异度93.1%，抗CarP抗体、抗环瓜氨酸多肽(cyclic peptide containing citrulline，CCP)抗体及类风湿因子(rheumatoid factor，RF)三者联合检测时灵敏度82.3%、特异度96.5%。抗CarP抗体在血清阴性RA患者中的阳性率为44.4%(20/45)。单因素Logistic回归分析显示，年龄、C反应蛋白(C-reactive protein，CRP)、红细胞沉降率(erythrocyte sedimentation rate，ESR)、RF、葡萄糖-6-磷酸异构酶(glucose-6-phosphate isomerase，GPI)、抗CCP抗体、抗CarP抗体是RA发生的危险因素；多因素Logistic回归分析发现，抗CCP抗体、抗CarP抗体是RA发生的独立危险因素。Spearman相关性分析发现，抗CarP抗体与肿胀关节数、压痛关节数、ESR、28个关节的疾病活动度评分(disease activity score for 28 joints，DAS28)、临床疾病活动指数(clinical disease activity index，CDAI)、简化疾病活动指数(simplified disease activity index，SDAI)无明显相关性(P>0.05)。有骨侵蚀RA组患者(88例)抗CarP抗体浓度高于无骨侵蚀RA组(70例)，差异有统计学意义(P < 0.05)。结论: 抗CarP抗体对RA的诊断有一定的价值。RF、抗CCP抗体、抗CarP抗体三者联合检测可提高其诊断价值，抗CarP抗体可能是血清阴性RA的有效辅助诊断工具。RA患者血清中高水平的抗CarP抗体浓度可能提示骨侵蚀风险增加，应早期干预治疗，但仍需进一步队列研究随访观察。

关键词: 关节炎, 类风湿, 自身抗体, 诊断, 抗氨基甲酰化蛋白抗体

Abstract:

Objective: To investigate the expression level and application value of anti-carbamylated protein (CarP) antibody in rheumatoid arthritis (RA). Methods: Demographic data and laboratory test results of RA patients, non-RA patients and healthy controls in the physical examination center were reviewed from December 2018 to June 2019 in the Rheumatology and Immunology Department of the People' s Hospital of Xinjiang Uygur Autonomous Region. The serum concentrations of anti-CarP antibodies in all the subjects were measured by ELISA and statistically analyzed. Results: A total of 259 subjects were included in this study, including 158 in the RA group (45 serum-negative RA patients), 59 in the non-RA group and 42 in the healthy control group. The concentration of anti-CarP antibody in RA group [8.31 (5.22, 15.26) U/mL] was higher than that in non-RA group [4.50 (3.35, 5.89) U/mL] and healthy control group [3.46 (2.76, 4.92) U/mL]. The concentration of anti-CarP antibody in non-RA group was not significantly different from that in healthy control group (P=0.10). Receiver operating characteristic (ROC) curve analysis showed that the sensitivity of anti-CarP antibody in the diagnosis of RA was 58.2%, and the specificity was 93.1%. The sensitivity of the combined detection of anti-CarP antibody, anti-cyclic peptide containing citrulline (CCP) antibody and rheumatoid factor (RF) was 82.3%, and the specificity was 96.5%. The positive rate of anti-CarP antibody in serum-negative RA patients was 44.4% (20/45). Univariate Logisitic regression analysis showed that age, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), RF, glucose-6-phosphate isomerase (GPI), anti-CCP antibody and anti-CarP antibody were risk factors for RA. Multivariate Logisitic regression analysis showed that anti-CCP antibody and anti-CarP antibody were independent risk factors for RA. Spearman correlation analysis showed that there was no significant correlation between anti-CarP antibody and swollen joint count (SJC), tenderness joints count (TJC), ESR, disease activity score for 28 joints (DAS28), clinical disease activity index (CDAI), simplified disease activity index (SDAI). The concentration of anti-CarP antibody in RA with bone erosion (n=88) was higher than that in RA without bone erosion (n=70), and there was significant difference between the two groups (P < 0.05). Conclusions: Anti-CarP antibody is an effective serological marker for the diagnosis of RA. The combined detection of RF, anti-CCP antibody and anti-CarP antibody can improve its diagnostic value, and anti-CarP antibody may be an effective assistant diagnostic tool for serum negative RA. The high serum concentration of anti-CarP antibody in patients with RA may indicate an increased risk of bone erosion and should be treated early, but further cohort studies are needed for follow-up observation.

Key words: Arthritis, rheumatoid, Autoantibodies, Diagnosis, Anti-carbamylated protein antibody

中图分类号:

R593.22

李正芳,罗采南,武丽君,吴雪,孟新艳,陈晓梅,石亚妹,钟岩. 抗氨基甲酰化蛋白抗体在诊断类风湿关节炎中的应用价值[J]. 北京大学学报（医学版）, 2024, 56(4): 729-734.

Zhengfang LI,Cainan LUO,Lijun WU,Xue WU,Xinyan MENG,Xiaomei CHEN,Yamei SHI,Yan ZHONG. Application value of anti-carbamylated protein antibody in the diagnosis of rheumatoid arthritis[J]. Journal of Peking University (Health Sciences), 2024, 56(4): 729-734.

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Items	AUC	95%CI	Sensitivity/%	Specificity/%	P
Anti-CarP	0.81	0.76-0.86	58.2	93.1	<0.001
Anti-CCP	0.84	0.79-0.89	71.5	96.0	< 0.001
RF	0.74	0.68-0.79	63.9	85.1	< 0.001
RF+Anti-CCP	0.81	0.76-0.86	71.5	96.0	< 0.01
Anti-CarP+RF	0.86	0.81-0.90	81.0	73.3	< 0.01
Anti-CarP+Anti-CCP	0.91	0.87-0.94	82.3	94.1	< 0.01
Anti-CarP+Anti-CCP+RF	0.92	0.88-0.95	82.3	96.5	< 0.01

Items	OR (95%CI)	P
Age	1.020 (1.001-1.039)	0.043
CRP	1.055 (1.028-1.082)	< 0.001
ESR	1.059 (1.040-1.078)	< 0.001
RF	1.014 (1.007-1.020)	< 0.001
GPI	2.776 (1.444-5.336)	0.002
Anti-CarP	1.022 (1.011-1.033)	< 0.001
Anti-CCP	1.489 (1.308-1.696)	< 0.001

Disease activity indicators	r	P
SJC	0.06	0.45
TJC	0.06	0.49
CRP	0.24	0.00
ESR	0.09	0.24
DAS28-ESR	0.08	0.33
DAS28-CRP	0.13	0.12
CDAI	0.06	0.45
SDAI	0.09	0.28

Items	Without bone erosion (n=70)	With bone erosion (n=88)	Statistics	P
Female, n(%)	51 (72.80)	74 (84.10)	2.98	0.08
Age/years, $\bar x \pm s$	45.63±12.36	55.64±11.47	-5.26	< 0.01
Course of the disease/months, M(P₂₅, P₇₅)	7.0 (3.0, 16.5)	36.0 (8.0, 120.0)	-5.67	< 0.01
BMI/(kg/m²), $\bar x \pm s$	23.28±3.11	24.02±4.22	-1.17	0.24
ESR/(mm/h), $\bar x \pm s$	37.00 ±21.47	41.66±21.29	-1.36	0.17
CRP/(mg/L), M(P₂₅, P₇₅)	6.45 (2.50, 26.70)	9.05 (3.20, 31.07)	-1.28	0.19
DAS28-ESR, $\bar x \pm s$	4.54±1.30	4.71±1.26	-0.85	0.39
DAS28-CRP, $\bar x \pm s$	3.95±1.29	4.08±1.24	-0.64	0.52
Anti-CarP/(U/mL), M(P₂₅, P₇₅)	7.66 (4.95, 12.75)	9.39 (5.65, 17.35)	-2.06	0.03