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Journal of Peking University(Health Sciences) ›› 2019, Vol. 51 ›› Issue (6): 1019-1024. doi: 10.19723/j.issn.1671-167X.2019.06.007

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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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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)

CLC Number: 

  • R593.24

Table 1

Clinical and demographic features of SLE patients"

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)

Figure 1

Prevalence of anti-CarP antibodies in patients with SLE SLE, systemic lupus erythematosus; HC, health control."

Table 2

Comparison of clinical and laboratory features between patients with anti-CarP and those without anti-CarP antibodies"

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

Table 3

Comparison of abnormal laboratory features between patients with anti-CarP and those without anti-CarP antibodies"

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

Table 4

Correlation between anti-CarP IgG and the laboratory parameters in patients with SLE"

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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