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北京大学学报（医学版） ›› 2019, Vol. 51 ›› Issue (6): 1019-1024. doi: 10.19723/j.issn.1671-167X.2019.06.007

• 论著 • 上一篇    下一篇

抗类瓜氨酸化抗体在系统性红斑狼疮中的意义

李英妮,相晓红,赵静,李云,孙峰,王红彦,贾汝琳,胡凡磊()   

  1. 北京大学人民医院风湿免疫科,北京 100044
  • 收稿日期:2019-08-10 出版日期:2019-12-18 发布日期:2019-12-19
  • 通讯作者: 胡凡磊 E-mail:fanleihu@bjmu.edu.cn
  • 基金资助:
    国家自然科学基金(81671604);国家自然科学基金(81302554);国家自然科学基金(31530020);北京市科技新星计划(Z181100006218044);北京大学临床医学+X青年项目-中央高校基本科研业务费(PKU2019LCXQ018)

Significance of anti-carbamylated fibrinogen antibodies in systemic lupus erythematosus

Ying-ni LI,Xiao-hong XIANG,Jing ZHAO,Yun LI,Feng SUN,Hong-yan WANG,Ru-lin JIA,Fan-lei HU()   

  1. Department of Rheumatology & Immunology, Peking University People’s Hospital, Beijing 100044, China
  • Received:2019-08-10 Online:2019-12-18 Published:2019-12-19
  • Contact: Fan-lei HU E-mail:fanleihu@bjmu.edu.cn
  • Supported by:
    Supported by the National Natural Science Foundation of China (81671604, 81302554, 31530020)(81671604);Supported by the National Natural Science Foundation of China (81671604, 81302554, 31530020)(81302554);Supported by the National Natural Science Foundation of China (81671604, 81302554, 31530020)(31530020);the Beijing Nova Program(Z181100006218044);the Fundamental Research Funds for Central Universities: Peking University Clinical Medcine Plus X-Young Scholars Project(PKU2019LCXQ018)

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摘要：

目的 探讨抗类瓜氨酸化抗体(anti-carbamylated fibrinogen antibodies, 抗CarP抗体)在系统性红斑狼疮(systemic lupus erythematosus,SLE)中的意义,SLE是否与类风湿关节炎(rheumatoid arthritis, RA)一样,存在大量针对类瓜氨酸的自身抗体,抗CarP抗体与关节损伤及疾病活动度高度相关。方法 利用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测105例确诊的SLE患者和73例健康对照者血清中抗CarP抗体水平,收集其他SLE相关临床和实验室数据,采用SPSS 24.0软件进行相应统计学分析。结果 SLE中存在抗CarP抗体,且明显高于健康对照组(P<0.05)。抗CarP抗体阳性组与阴性组SLE患者相比,在以下临床及实验室指标方面差异有统计学意义:病程、血沉(erythrocyte sedimentation rate,ESR)、C-反应蛋白(C-reactive protein,CRP)、类风湿因子(rheumatoid factor,RF)、抗心磷脂抗体、抗dsDNA抗体、D-二聚体、IgA、IgG、补体C3、补体C4、外周血红细胞计数和血红蛋白水平(P<0.05)。与SLE其他自身抗体相比,抗CarP抗体的阳性率(21.9%)高于抗Sm抗体(15.24%),与抗核糖体P蛋白抗体(22.86%)阳性率相似;在SLE特异性抗体阴性的患者中可检测到抗CarP抗体,其阳性率分别为: 抗Sm(-)组20.2%(18/89),抗dsDNA(-)组9.3%(4/43),抗核小体抗体(-)组12.5%(6/48)和抗核糖体P蛋白抗体(-)组20.9%(17/81)。而且,抗CarP抗体水平与病程、补体C3、补体C4、红细胞及血红蛋白呈明显负相关(P<0.05),与ESR、CRP、IgA、IgG、RF、抗心磷脂抗体、抗dsDNA抗体及D-二聚体呈明显正相关(P<0.05)。结论 SLE患者血清中抗CarP抗体水平升高,抗CarP抗体与SLE患者临床及实验室指标具有相关性。

关键词: 系统性红斑狼疮, 自身抗体, 类瓜氨酸化抗体(抗CarP抗体)

Abstract:

Objective: Antibodies against carbamylated protein (anti-CarP) were found to be a promising marker to evaluate joint damage and disease activity in patients with rheumatoid arthritis (RA). However, whether anti-CarP antibodies were present in systemic lupus erythematosus (SLE) remained ambiguity. We have therefore undertaken this study to assess the levels of serum anti-CarP antibodies and to evaluate their clinical value in SLE.Methods: Serum levels of antibodies against carbamylated-fibrinogen (anti-CarP) were measured by enzyme-linked immunosorbent assay (ELISA) in 105 SLE patients and 73 healthy controls. Other clinical and laboratory measurements of the SLE patients were collected from medical records. Data analyses between anti-CarP antibodies and other laboratory measurements were performed using SPSS software for Windows 24.0.Results: The levels of serum anti-CarP antibodies in the patients with SLE were significantly higher than those in the healthy controls (P<0.05). There were significant differences between the anti-CarP-positive group and anti-CarP-negative group in many clinical features. The disease duration, values of ESR, CRP, RF, anti-cardiolipin, anti-dsDNA, D-dipolymer, IgA and IgG were significantly higher in the anti-CarP-positive group compared with the negative group (P<0.05). Conversely, the values of complement 3, complement 4, peripheral blood RBC, and hemoglobin were significantly lower in anti-CarP-positive group than in the negative group(P<0.05). Moreover, the incidence of increase of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), D-dipolymer, decrease of peripheral blood RBC, hemoglobin, complement 3, complement 4, and positive rate of anti-dsDNA were significant different between the two groups(P<0.05). The positive rate of anti-CarP (21.9%) was higher than that of anti-Sm (15.24%), and close to anti-ribosomal P protein (22.86%) in our SLE patients. In addition, anti-CarP antibody was present in the SLE patients lacking the disease specific antibodies, including anti-Sm (anti-CarP positive rate 20.2%, 18/89), anti-dsDNA (anti-CarP positive rate 9.3%, 4/43), anti-nucleosome (anti-CarP positive rate 12.5%, 6/48), and anti-ribosomal P protein antibody (anti-CarP positive rate 20.9%, 17/81). Moreover, the high levels of anti-CarP antibodies were correlated with short disease duration, low C3, C4, RBC, and hemoglobin (P<0.05), high ESR, CRP, IgA, IgG, RF, anti-cardiolipin, anti-dsDNA, and D-dipolymer (P<0.05).Conclusion: The level of anti-CarP antibody was increased in the serum of patients with SLE. There were correlations between anti-CarP antibodies and clinical and laboratory indicators of SLE patients.

Key words: Systemic lupus erythematosus, Antoantibodies, Anti-carbamylated fibrinogen antibodies (anti-CarP)

中图分类号: 

  • R593.24

表1

SLE患者一般临床资料"

Items Data (n=105)
Age/years, x?±s 34.12±11.76
Women, n (%) 95 (90.5)
Disease duration/years, median (range) 6 (0-27)
Fever (>38 ℃), n (%) 51 (48.6)
Rash, n (%) 39 (37.1)
Alopecia, n (%) 43 (41)
Oral ulcer, n (%) 22 (21)
Proteinuria (>0.5 g/24 h), n (%) 53 (50.5)
Arthritis, n (%) 23 (21.9)
Neuropsychiatric symptom, n (%) 7 (6.7)

图1

SLE与HC中抗CarP抗体水平的比较"

表2

抗CarP抗体阳性组与抗CarP抗体阴性组SLE患者临床及实验室指标差异"

Items Anti-CarP IgG(+), n=23 Anti-CarP IgG(-), n=82 P
Women, n (%) 21(91.3) 74(90.2) -
Age/years, x?±s 34.86±12.82 33.91±11.52 0.733
Disease duration/ years, median (range) 2(0-22) 0.08(6-27) 0.034
Fever (>38℃), n (%) 15(65.2) 36(43.9) 0.058
Rash, n (%) 8(34.8) 31(37.8) 0.496
Alopecia, n (%) 10(43.5) 33(40.2) 0.481
Oral ulcer, n (%) 2(8.7) 20(24.4) 0.084
Arthritis, n (%) 5(21.7) 17(20.7) 0.561
Serositis, n (%) 1(4.3) 4(4.9) 0.716
Neuropsychiatric symptom, n (%) 1(4.3) 6(7.3) 0.521
ESR/(mm/h), median (range) 78(11-126) 23(1-137) <0.000 1
CRP/(mg/L), median (range) 6.9(1-69) 2.9(1-89) 0.034
C3/(g/L), x?±s 0.41±0.24 0.68±0.29 <0.000 1
C4/(g/L), median (range) 0.05(0.02-0.34) 0.13(0-0.34) <0.000 1
RF/(IU/mL), median (range) 27.2(20-603) 20(18-201) <0.000 1
Anti-Sm, n (%) 4(17.4) 9(10.9) 0.671
ANA, n (%) 22(95.7) 75(91.5) 1.0
SLEDAI, median (range) 8(3-13) 8(0-50) 0.537
Anti-cardiolipin/(RU/mL), median (range) 9.6(0.1-133.6) 5.7(0.1-108.9) 0.003
Anti-dsDNA/(IU/mL), median (range) 416.6 (51.6-1 012.7) 133.8 (0.1-1 040.4) 0.002
Anti-nuclesome/(IU/mL), median (range) 41.65(5-200) 42.99(1-200) 0.287
Anti-ribosomal P protein/(IU/mL), median (range) 12.8(2-143) 8.8(0-200) 0.801
D-dipolymer/(μg/L), median (range) 779(38-6 920) 197(14-2 398) 0.001
IgA/(g/mL), x?±s 3.42±1.96 2.27±1.19 0.001
IgG/(g/mL), x?±s 24.53±10.57 12.25±5.43 <0.000 1
IgM/(g/mL), median (range) 0.74(0.08-2.39) 0.65(0.11-3.96) 0.151
PLT/(×109/L), x?±s 186.59±99.67 163.41±72.95 0.219
WBC/(×109/L), x?±s 5.63±2.75 5.83±2.78 0.770
RBC/ (×1012/L), x?±s 3.17±0.58 3.66±0.80 0.007
Hemoglobin/(g/mL), x?±s 95.60±14.17 113.99±20.82 <0.000 1
Uric acid/(μmol/L), x?±s 326.5±151.3 340.7±116.0 0.639
Blood urea/(mmol/L), median (range) 4.65(2.02-25.37) 5.35 (1.98-27.14) 0.731
Blood creatinine/(μmol/L), median (range) 59(33-260) 57(32-2 499) 0.875
Proteinuria for 24 h/(g/d), median (range) 0.72(0.04-6.87) 0.53(0-95.70) 0.433

表3

抗CarP抗体阳性组与抗CarP抗体阴性组SLE患者实验室指标异常的比较"

Items Anti-CarP IgG(+)(n=23) Anti-CarP IgG(-)(n=82) P
ESR high levels (>20 mm/h), n (%) 20 (87) 42 (54.5) 0.005
CRP high levels (>7.9 mg/L), n (%) 8 (34.8) 18 (21.9) 0.111
C3, low levels (<0.88 g/L), n (%) 21 (91.3) 58 (70.7) 0.046
C4, low levels (<0.15 g/L), n (%) 19 (82.6) 46 (56.1) 0.013
IgA, elevated levels (>3.78 g/mL), n (%) 8 (34.8) 7 (8.5) 0.002
RF, elevated levels (>30 IU/mL), n (%) 8 (34.8) 12 (14.6) 0.046
Anti-cardiolipin, elevated levels (>12 RU/mL), n (%) 7 (30.4) 11 (13.4) 0.099
IgG, elevated levels (>16.18 g/mL), n (%) 17 (73.9) 13 (15.9) <0.001
Anti-dsDNA, elevated levels (>100 IU/mL), n (%) 19 (82.6) 39 (47.6) 0.001
D-dipolymer, elevated levels (>250 μg/L), n (%) 17 (73.9) 34 (41.5) 0.001
RBC, low levels (<3.5×109/L), n (%) 15 (65.2) 28 (34.1) 0.004
Hemoglobin, low levels (<110 g/L), n (%) 17 (73.9) 33 (40.2) 0.002

表4

SLE患者血清抗CarP抗体与临床和实验室指标间的相关性"

Items Spearman rank test Spearman partial correlation
r P R P
Disease duration -0.210 0.032 -0.060 0.572
Hemoglobin -0.438 <0.001 -0.323 0.002
Anti-cardiolipin 0.349 <0.001 0.302 0.004
Anti-dsDNA 0.384 <0.001 0.256 0.015
RF 0.466 <0.001 0.475 <0.001
ESR 0.502 <0.001 0.440 <0.001
CRP 0.195 0.048 -0.004 0.970
C3 -0.351 <0.001 -0.377 <0.001
C4 -0.356 <0.001 -0.366 <0.001
IgA 0.380 <0.001 0.365 <0.001
IgG 0.601 <0.001 0.651 <0.001
RBC -0.36 <0.001 -0.263 0.012
D-dipolymer 0.357 <0.001 0.539 <0.001
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