抗内皮细胞抗体检测在早期流产中的预测价值

doi:10.19723/j.issn.1671-167X.2023.06.013

摘要/Abstract

摘要：

目的: 探讨抗内皮细胞抗体(anti-endothelial cell antibodies, AECA)预测早期流产的临床意义。方法: 选取2020年1月至2022年12月于北京大学人民医院进行产检并完善AECA的无自身免疫病史孕妇122例。根据早期流产史(流产时孕周＜12周)，将研究对象分为早期流产组和对照组，采用t检验、非参数Wilcoxon检验、Chi-square检验、Fisher确切概率法比较两组一般资料和实验室指标，多因素Logistic回归模型分析早期流产的相关因素。随访孕妇的自然流产情况，Kaplan-Meier生存分析比较AECA阳性和AECA阴性孕妇的自然流产率。结果: (1) 共纳入122例孕妇，其中早期流产组35例(28.7%)，平均年龄(32.1±6.1)岁；对照组87例(71.3%)，平均年龄(30.7±5.1)岁。早期流产组有更多的妊娠次数[3 (2, 4) vs. 1 (1, 2), Z=-6.402, P < 0.001]和高血压合并症(11.4% vs.1.1%, P=0.024)。早期流产组AECA的阳性率(34.3% vs. 8.0%, χ²=13.070, P < 0.001)和免疫球蛋白G升高的比例(17.1% vs. 4.6%, P=0.032)显著高于对照组。(2)多因素Logistic回归分析结果显示，妊娠次数增加(OR=4.149, 95%CI: 2.287~7.529, P < 0.001)、AECA阳性(OR=4.288, 95%CI: 1.157~15.893, P=0.029)、免疫球蛋白G升高(OR=6.177, 95%CI: 1.156~33.015, P=0.033)是早期流产的危险因素。(3)将122例孕妇分为AECA阳性组(19例)和AECA阴性组(103例)，生存分析显示，孕12周时AECA阳性组的胎儿生存率显著低于AECA阴性组(84.2% vs. 96.1%, P=0.035)。结论: 妊娠次数增加、AECA阳性及免疫球蛋白G升高是导致早期流产的显著危险因素；AECA的检测有助于预测早期流产，可以为改善妊娠结局提供依据。

关键词: 抗内皮细胞抗体, 早期流产, 危险因素

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

中图分类号:

R593.2

罗靓,李云,王红彦,相晓红,赵静,孙峰,张晓盈,贾汝琳,李春. 抗内皮细胞抗体检测在早期流产中的预测价值[J]. 北京大学学报（医学版）, 2023, 55(6): 1039-1044.

Liang LUO,Yun LI,Hong-yan WANG,Xiao-hong XIANG,Jing ZHAO,Feng SUN,Xiao-ying ZHANG,Ru-lin JIA,Chun LI. Anti-endothelial cell antibodies in predicting early miscarriage[J]. Journal of Peking University (Health Sciences), 2023, 55(6): 1039-1044.

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参考文献 26

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.

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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

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

Variables	Univariate					Multivariate
Variables	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