Email Alert | RSS

Journal of Peking University (Health Sciences) ›› 2023, Vol. 55 ›› Issue (6): 1039-1044. doi: 10.19723/j.issn.1671-167X.2023.06.013

Previous Articles     Next Articles

Anti-endothelial cell antibodies in predicting early miscarriage

Liang LUO1,2,Yun LI1,Hong-yan WANG1,Xiao-hong XIANG1,Jing ZHAO1,Feng SUN1,Xiao-ying ZHANG1,*(),Ru-lin JIA1,*(),Chun LI1   

  1. 1. Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing 100044, China
    2. Department of Chinese Medicine, the People's Hospital of Yubei District of Chongqing City, Chongqing 401120, China
  • Received:2023-08-20 Online:2023-12-18 Published:2023-12-11
  • Contact: Xiao-ying ZHANG,Ru-lin JIA E-mail:zhangxiaoying@pkuph.edu.cn;1036013457@qq.com
  • Supported by:
    the China International Medical Foundation(Z-2018-40-2101);Peking University People' s Hospital Scientific Research Development Funds(RD 2022-66)

RICH HTML

   

PDF (PC)

Abstract:

Objective: To explore the clinical significance of anti-endothelial cell antibodies (AECA) in predicting early miscarriage. Methods: A total of 122 pregnant women with no history of autoimmune diseases who underwent prenatal examination at Peking University People's Hospital from January 2020 to December 2022 were selected, and they were tested for AECA. Based on the history of early miscarriage (gestational age at miscarriage < 12 weeks), the participants were divided into an early miscarriage group and a control group. t-tests, non-parametric Wilcoxon tests, Chi-square tests, and Fisher's exact probability method were used to compare general information and laboratory indicators between the two groups. A multivariate Logistic regression model was used to analyze the factors associated with early miscarriage. The natural miscarriage rates were assessed through follow-up with pregnant women, and Kaplan-Meier survival analysis was employed to compare the natural miscarriage rates between AECA-positive and AECA-negative pregnant women. Results: (1) A total of 122 pregnant women were enrolled, comprising 35 cases (28.7%) in the early miscarriage group, with an average age of (32.1±6.1) years, and 87 cases (71.3%) in the control group, with an average age of (30.7±5.1) years. The early miscarriage group had higher gravidity [3 (2, 4) vs. 1 (1, 2), Z=-6.402, P < 0.001] and a higher prevalence of hypertension (11.4% vs.1.1%, P=0.024). The positive rate of AECA in the early miscarriage group (34.3% vs. 8.0%, χ2=13.070, P < 0.001) and the proportion of elevated immunoglobulin G (17.1% vs. 4.6%, P=0.032) were significantly higher than that in the control group. (2) Multivariate logistic regression analysis showed that higher gravidity (OR=4.149, 95%CI: 2.287-7.529, P < 0.001), AECA positivity (OR= 4.288, 95% CI: 1.157-15.893, P=0.029), and elevated immunoglobulin G levels (OR =6.177, 95%CI: 1.156-33.015, P=0.033) were risk factors for early miscarriage. (3) The 122 pregnant women were categorized into two groups: the AECA-positive group (19 cases) and the AECA-negative group (103 cases). Survival analysis demonstrated that at the end of 12 weeks of gestation, the fetal survival rate in the AECA-positive group was significantly lower than that in the AECA-negative group (84.2% vs. 96.1%, P= 0.035). Conclusion: Higher gravidity, AECA positivity, and elevated immunoglobulin G levels are significant risk factors for early miscarriage. The results demonstrate that AECA is a novel predicting test in early miscarriage.

Key words: Anti-endothelial cell antibodies, Early miscarriage, Risk factors

CLC Number: 

  • R593.2

Table 1

Comparisons of demographic characteristics between the early miscarriage group and control group"

Variables Early miscarriage group (n=35) Control group (n=87) Z/t/χ2 P
Age/years, ${\bar x}$±s 32.1±6.1 30.7±5.1 -1.129 0.264
Age at first conception/years, ${\bar x}$±s 26.9±5.1 28.0±4.6 1.125 0.265
Number of pregnancies, M (P25，P75) 3 (2, 4) 1 (1, 2) -6.402 < 0.001
Artificial insemination, n (%) 8 (22.9) 12 (13.8) 1.496 0.221
Hyperthyroidism, n (%) 0 (0) 1 (1.1) N/A >0.999
Hypothyroidism, n (%) 6 (17.1) 7 (8.0) 1.319 0.251
Hypertension, n (%) 4 (11.4) 1 (1.1) N/A 0.024
Diabetes, n (%) 2 (5.7) 1 (1.1) N/A 0.198
Hyperlipidemia, n (%) 0 (0) 2 (2.3) N/A >0.999
Uterine fibroids, n (%) 2 (5.7) 12 (13.8) N/A 0.346
Malignant tumor, n (%) 4 (11.4) 2 (2.3) N/A 0.056

Table 2

Comparison of laboratory indexes between the early miscarriage group and control group"

Variables Early miscarriage group (n=35) Control group (n=87) Z/t/χ2 P
WBC/(×109/L), ${\bar x}$±s 8.3 ± 4.5 8.9 ± 4.2 0.663 0.510
HGB/(g/L), ${\bar x}$±s 108.7 ± 24.2 110.3± 23.1 0.339 0.736
PLT/ (×109/L), ${\bar x}$±s 136.6 ± 89.3 171.3 ± 95.5 1.898 0.062
TG/(mmol/L)，${\bar x}$±s 2.7 ± 1.2 2.8 ± 1.9 0.384 0.702
HDL-C/(mmol/L), ${\bar x}$±s 1.6 ± 0.4 1.7 ± 0.5 1.383 0.171
LDL-C/(mmol/L), ${\bar x}$±s 3.1 ± 1.3 3.2 ± 1.0 0.211 0.834
T3/(μg/dL), ${\bar x}$±s 96.6 ± 48.4 121.0 ± 38.2 1.351 0.196
T4/(μg/dL), ${\bar x}$±s 8.6 ± 3.1 10.7 ± 3.7 1.582 0.128
ANA positive, n (%) 2 (5.7) 3 (3.4) N/A 0.624
AECA positive, n (%) 12 (34.3) 7 (8.0) 13.070 < 0.001
Anti-SSA antibody positive, n (%) 3 (8.6) 2 (2.3) N/A 0.142
Anti-SSB antibody positive, n (%) 2 (5.7) 0 (0) N/A 0.081
Anti-dsDNA antibody positive, n (%) 0 (0) 1 (1.1) N/A >0.999
Anti-U1-RNP antibody positive, n (%) 1 (2.9) 0 (0) N/A 0.287
Low C3, n (%) 4 (11.4) 8 (9.2) N/A 0.741
Low C4, n (%) 7 (20.0) 17 (19.5) 0.003 0.954
Elevated IgA, n (%) 0 (0) 2 (2.3) N/A >0.999
Elevated IgG, n (%) 6 (17.1) 4 (4.6) N/A 0.032
Elevated IgM, n (%) 1 (2.9) 3 (3.4) N/A >0.999
D-dimer/(μg/L), M (P25，P75) 412.5 (207.5, 791.0) 588.0 (346.0, 1138.8) -0.726 0.468

Table 3

Results of binary logistic regression analysis for early miscarriage"

Variables Univariate Multivariate
B Wald P OR 95%CI B Wald P OR 95%CI
Number of pregnancies 1.432 25.573 < 0.001 4.188 2.404-7.295 1.423 21.906 < 0.001 4.149 2.287-7.529
Hypertension 2.407 4.476 0.034 11.097 1.194-103.141
PLT/(×109/L) -0.004 3.288 0.070 0.996 0.992-1.000
AECA positive 1.786 11.292 0.001 5.963 2.105-16.889 1.456 4.743 0.029 4.288 1.157-15.893
Elevated IgG 1.457 4.583 0.032 4.293 1.131-16.296 1.821 4.534 0.033 6.177 1.156-33.015

Figure 1

Comparison of fetal survival rates between AECA-positive pregnant women and AECA-negative pregnant women ACEA, anti-endothelial cell antibodies."

1 Madendag IC , Sahin ME , Madendag Y , et al. Evaluation of the levels of secretory leukocyte protease inhibitor in the cervical mucus of women with unexplained infertility[J]. J Obstet Gynaecol Res, 2020, 46 (7): 1128- 1132.
doi: 10.1111/jog.14299
2 Yang XL , Chen F , Yang XY , et al. Efficacy of low-molecular-weight heparin on the outcomes of in vitro fertilization/intracytoplasmic sperm injection pregnancy in non-thrombophilic women: A meta-analysis[J]. Acta Obstet Gynecol Scand, 2018, 97 (9): 1061- 1072.
doi: 10.1111/aogs.13359
3 Quenby S , Gallos ID , Dhillon-Smith RK , et al. Miscarriage matters: The epidemiological, physical, psychological, and economic costs of early pregnancy loss[J]. Lancet, 2021, 397 (10285): 1658- 1667.
doi: 10.1016/S0140-6736(21)00682-6
4 Jiang L , Xu X , Cao Z , et al. Comparison of frozen embryo transfer outcomes between uterine infusion of granulocyte colony-stimulating factor and growth hormone application in patients with thin endometrium: A retrospective study[J]. Front Endocrinol (Lausanne), 2021, 12, 725202.
doi: 10.3389/fendo.2021.725202
5 Qu P , Yan M , Zhao D , et al. Association between pre-pregnancy body mass index and miscarriage in an assisted reproductive technology population: A 10-year cohort study[J]. Front Endocrinol (Lausanne), 2021, 12, 646162.
doi: 10.3389/fendo.2021.646162
6 Shankarkumar U , Pradhan VD , Patwardhan MM , et al. Autoantibody profile and other immunological parameters in recurrent spontaneous abortion patients[J]. Niger Med J, 2011, 52 (3): 163- 166.
doi: 10.4103/0300-1652.86126
7 Lindqvist KJ , Osterland CK . Human antibodies to vascular endothelium[J]. Clin Exp Immunol, 1971, 9 (6): 753- 760.
8 Alessandri C , Bombardieri M , Valesini G . Pathogenic mechanisms of anti-endothelial cell antibodies (AECA): Their prevalence and clinical relevance[J]. Adv Clin Chem, 2006, 42, 297- 326.
9 杜欣莹, 管立学, 王美, 等. 血清抗内皮细胞抗体定量分析与复发性自然流产相关性研究[J]. 中国优生与遗传杂志, 2009, 17 (6): 23- 25.
10 Cacciola R , Gentilini Cacciola E , Vecchio V , et al. Impact of anti-endothelial cell antibodies (AECAs) in patients with polycythemia vera and thrombosis[J]. Diagnostics (Basel), 2022, 12 (5): 1077.
doi: 10.3390/diagnostics12051077
11 Roussev RG , Stern JJ , Kaider BD . Anti-endothelial cell antibo-dies: Another cause for pregnancy loss?[J]. Am J Reprod Immunol, 1998, 39 (2): 89- 95.
doi: 10.1111/j.1600-0897.1998.tb00340.x
12 蒋莎, 李娜, 张杨, 等. Toll样受体4通过调节性T细胞引起不明原因复发性流产的机制研究进展[J]. 中华生殖与避孕杂志, 2018, 38 (10): 6.
13 Zilla P , von Oppell U , Deutsch M . The endothelium: A key to the future[J]. J Card Surg, 1993, 8 (1): 32- 60.
doi: 10.1111/j.1540-8191.1993.tb00574.x
14 Youinou P , Le Dantec C , Bendaoud B , et al. Endothelium, a target for immune-mediated assault in connective tissue disease[J]. Autoimmun Rev, 2006, 5 (3): 222- 228.
doi: 10.1016/j.autrev.2005.06.012
15 张梦莹, 李志, 吕坤, 等. 系统性红斑狼疮患者血清抗内皮细胞抗体和抗β2糖蛋白Ⅰ抗体水平及其对人脐静脉内皮细胞增殖的影响[J]. 中国临床药理学与治疗学, 2013, 18 (2): 142- 146.
16 Hussain M , Chen P , Zhang Y , et al. Moesin expression is correlated with its involvement in patients with Behcet' s disease[J]. Arch Med Sci, 2020, 16 (4): 924- 930.
17 Mutoh T , Shirai T , Ishii T , et al. Identification of two major autoantigens negatively regulating endothelial activation in Takayasu arteritis[J]. Nat Commun, 2020, 11 (1): 1253.
18 Meyer O , Kaiser P , Haim T , et al. Anti-vascular endothelial cell antibodies (AECA): Comparison of two assay methods and clinical applications[J]. Rev Rhum Engl Ed, 1995, 62 (11): 737- 747.
19 Blank M , Krause I , Goldkorn T , et al. Monoclonal anti-endothe-lial cell antibodies from a patient with Takayasu arteritis activate endothelial cells from large vessels[J]. Arthritis Rheum, 1999, 42 (7): 1421- 1432.
20 Thomas AM , Gerogianni A , McAdam MB , et al. Complement component C5 and TLR molecule CD14 mediate heme-induced thromboinflammation in human blood[J]. J Immunol, 2019, 203 (6): 1571- 1578.
21 Belizna C , Duijvestijn A , Hamidou M , et al. Antiendothelial cell antibodies in vasculitis and connective tissue disease[J]. Ann Rheum Dis, 2006, 65 (12): 1545- 1550.
22 母洪洪, 张湘燕, 张程. 抗内皮细胞抗体检测临床应用研究进展[J]. 现代医药卫生, 2020, 36 (30): 374- 376.
23 Akhtar MA , Agrawal R , Brown J , et al. Thyroxine replacement for subfertile women with euthyroid autoimmune thyroid disease or subclinical hypothyroidism[J]. Cochrane Database Syst Rev, 2019, 6 (6): CD011009.
24 Arachchillage D , Pericleous C . Evolution of antiphospholipid syndrome[J]. Semin Thromb Hemost, 2023, 49 (3): 295- 304.
25 Poorolajal J , Cheraghi P , Cheraghi Z , et al. Predictors of miscarriage: A matched case-control study[J]. Epidemiol Health, 2014, 36, e2014031.
26 Walter K . Early pregnancy loss[J]. JAMA, 2023, 329 (16): 1426.
[1] Hui WEI, Jingfeng ZHANG, Zhongqiang YAO, Jinxia ZHAO. Clinical characteristics and relevant factors of rheumatoid arthritis patients with anemia of chronic disease [J]. Journal of Peking University (Health Sciences), 2026, 58(2): 307-312.
[2] Jie ZHAO, Chun FU, Xiujuan ZHAO, Haiyan XUE, Shu LI, Zhenzhou WANG, Fengxue ZHU. Risk factors for ventilator-associated pneumonia in patients with chest trauma in intensive care unit [J]. Journal of Peking University (Health Sciences), 2026, 58(2): 351-358.
[3] Bowen LI, Qiang ZHANG, Yixin SUN. Establishment and validation of a risk prediction model for scoliosis after Nuss procedure in children and young adults with pectus excavatum [J]. Journal of Peking University (Health Sciences), 2025, 57(5): 941-946.
[4] Xiaoyong YANG, Fan ZHANG, Lulin MA, Cheng LIU. Clinical characteristics and influencing factors of extraglandular invasion of prostatic ductal adenocarcinoma [J]. Journal of Peking University (Health Sciences), 2025, 57(5): 956-960.
[5] Wei LIU, Wen GUO, Zhe GUO, Chunyan LI, Yunlong LI, Siqi LIU, Liang ZHANG, Hui SONG. Risk factors associated with non-radiographic bone erosion in patients with gout [J]. Journal of Peking University (Health Sciences), 2025, 57(4): 735-739.
[6] Mengxi LU, Qiuping LIU, Tianjing ZHOU, Xiaofei LIU, Yexiang SUN, Peng SHEN, Hongbo LIN, Xun TANG, Pei GAO. Association of triglyceride-glucose index and cardiovascular disease in a community-based Chinese cohort [J]. Journal of Peking University (Health Sciences), 2025, 57(3): 430-435.
[7] Huaqiu GUO, Zhe WANG, Xue YANG, Jie BAI. Clinical features and risk factors of patients with oral bleeding in dental emergency [J]. Journal of Peking University (Health Sciences), 2025, 57(1): 142-147.
[8] Minting DENG, Nan WANG, Bin XIA, Yuming ZHAO, Junxia ZHU. Factors associated with spontaneous re-eruption of traumatically intruded permanent anterior teeth in children and adolescents [J]. Journal of Peking University (Health Sciences), 2025, 57(1): 148-153.
[9] Yukai LI, Hongyan WANG, Liang LUO, Yun LI, Chun LI. Clinical significance of antiphospholipid antibodies in Behcet disease with thrombosis [J]. Journal of Peking University (Health Sciences), 2024, 56(6): 1036-1040.
[10] Yang TIAN, Yongzheng HAN, Jiao LI, Mingya WANG, Yinyin QU, Jingchao FANG, Hui JIN, Min LI, Jun WANG, Mao XU, Shenglin WANG, Xiangyang GUO. Incidence and risk factors of postoperative epidural hematoma following anterior cervical spine surgery [J]. Journal of Peking University (Health Sciences), 2024, 56(6): 1058-1064.
[11] Mingrui WANG, Jinhui LAI, Jiaxiang JI, Xinwei TANG, Haopu HU, Qi WANG, Kexin XU, Tao XU, Hao HU. Risk factors for decreased quality of life in patients with kidney stones predicted by the Chinese version of Wisconsin stone quality of life questionnaire [J]. Journal of Peking University (Health Sciences), 2024, 56(6): 1069-1074.
[12] Zhicun LI, Tianyu WU, Lei LIANG, Yu FAN, Yisen MENG, Qian ZHANG. Risk factors analysis and nomogram model construction of postoperative pathological upgrade of prostate cancer patients with single core positive biopsy [J]. Journal of Peking University (Health Sciences), 2024, 56(5): 896-901.
[13] Ye YAN,Xiaolong LI,Haizhui XIA,Xuehua ZHU,Yuting ZHANG,Fan ZHANG,Ke LIU,Cheng LIU,Lulin MA. Analysis of risk factors for long-term overactive bladder after radical prostatectomy [J]. Journal of Peking University (Health Sciences), 2024, 56(4): 589-593.
[14] Yan CHEN,Kuangmeng LI,Kai HONG,Shudong ZHANG,Jianxing CHENG,Zhongjie ZHENG,Wenhao TANG,Lianming ZHAO,Haitao ZHANG,Hui JIANG,Haocheng LIN. Retrospective study on the impact of penile corpus cavernosum injection test on penile vascular function [J]. Journal of Peking University (Health Sciences), 2024, 56(4): 680-686.
[15] Bo PANG,Tongjun GUO,Xi CHEN,Huaqi GUO,Jiazhang SHI,Juan CHEN,Xinmei WANG,Yaoyan LI,Anqi SHAN,Hengyi YU,Jing HUANG,Naijun TANG,Yan WANG,Xinbiao GUO,Guoxing LI,Shaowei WU. Personal nitrogen oxides exposure levels and related influencing factors in adults over 35 years old in Tianjin and Shanghai [J]. Journal of Peking University (Health Sciences), 2024, 56(4): 700-707.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright © Journal of Peking University (Health Sciences), All Rights Reserved.
Powered by Beijing Magtech Co. Ltd