抗磷脂抗体在白塞病合并血栓中的临床意义

doi:10.19723/j.issn.1671-167X.2024.06.014

摘要/Abstract

摘要：

目的: 探讨抗磷脂抗体(antiphospholipid antibody, aPL)在白塞病(Behcet disease, BD)合并血栓中的分布及其临床意义。方法: 回顾性选取2008年2月至2024年7月于北京大学人民医院风湿免疫科住院的222例BD患者作为研究对象，收集患者的一般资料(包括年龄、性别等)、临床表现(包括口腔溃疡、生殖器溃疡和血栓等)、实验室指标[包括aPL、人类白细胞抗原(human leukocyte antigen, HLA)-B51、抗内皮细胞抗体等]，随访合并血栓的BD患者血栓复发情况。使用卡方检验比较aPL阳性组和aPL阴性组患者的临床症状及实验室指标上的差异。使用Log-rank检验对aPL阳性组和aPL阴性组的血栓复发率进行比较，并用Two-stage方法进行P矫正，最后使用Graphpad prism进行绘图。结果: BD患者中，aPL单阳性、双阳性及三阳性患者的比例分别为22.1%、0.5% 和1.4%。抗心磷脂抗体、抗β2糖蛋白Ⅰ抗体和狼疮抗凝物(lupus anticoagulant, LAC)的阳性率分别为10.4%、1.8%和13.1%。aPL阳性组血栓的发生率显著高于aPL阴性组(44.9% vs. 16.9%, P < 0.001)。aPL阳性组的血红细胞沉降率[(20.78±4.91) mm/h vs. (15.85±4.29) mm/h, P=0.005]、C反应蛋白[(12.97±5.17) mg/L vs. (7.49±4.22) mg/L, P=0.010]和免疫球蛋白M [(1.55±0.95) g/L vs. (1.12±0.72) g/L, P < 0.001]显著高于aPL阴性组。LAC阳性是BD患者血栓发生的独立危险因素(OR=8.51, 95%CI: 2.71~26.72, P < 0.001)。aPL阳性组的血栓复发率高于aPL阴性组，但两组差异无统计学意义(69.23% vs. 52.17%, P=0.932)。结论: LAC阳性和动脉瘤是BD患者血栓形成的独立危险因素，aPL阳性也会显著增加BD患者血栓发生风险，对指导BD的治疗具有重要意义。

关键词: 抗磷脂抗体, 白塞病, 血栓, 复发, 危险因素

Abstract:

Objective: To investigate the distribution and clinical significance of antiphospholipid antibody (aPL) in patients with Behcet disease (BD). Methods: A total of 222 BD patients admitted to the Department of Rheumatology and Immunology in Peking University People' s Hospital from February 2008 to July 2024 were selected retrospectively. General data of the patients including age and gender were collec-ted. Clinical manifestations (including oral ulcers, genital ulcers, and thrombosis) and laboratory indexes (including aPL, human leukocyte antigen-B51, and anti-endothelial cell antibody) were collec-ted. The recurrence of thrombosis in the BD patients with thrombosis was followed up. Chi-square test was used to compare the clinical symptoms and laboratory indicators between aPL positive group and aPL negative group. Log-rank test was used to compare the recurrence rates of the aPL positive group and the aPL negative group, and P correction was performed by Two-stage method. Finally, Graphpad prism was used for plotting. Results: The prevalence of single aPL, double aPL and triple aPL positivity in the BD patients were 22.1%, 0.5% and 1.4%, respectively. The positive rates of anti-cardiolipin antibody, anti-β2 glycoprotein Ⅰ antibody and lupus anticoagulant (LAC) were 10.4%, 1.8% and 13.1%, respectively. The incidence of thrombosis in the aPL positive group was significantly higher than that in the aPL negative group (44.9% vs. 16.9%, P < 0.001). The erythrocyte sedimentation rate [(20.78±4.91) mm/h vs. (15.85±4.29) mm/h, P=0.005], C-reactive protein [(12.97±5.17) mg/L vs. (7.49± 4.22) mg/L, P=0.010] and IgM [(1.55±0.95) g/L vs. (1.12±0.72) g/L, P < 0.001] in the aPL positive group were significantly higher than those in the aPL negative group. LAC positivity was an independent risk factor for thrombosis in the BD patients (OR=8.51, 95%CI: 2.71-26.72, P < 0.001). The recurrence rate of the aPL positive group was higher than that of the aPL negative group, but there was no statistical difference (69.23% vs. 52.17%, P=0.932). Conclusion: Positive LAC and aneurysm are independent risk factors for thrombosis in BD patients. At the same time, positive antiphospholipid antibody can also significantly increase the risk of thrombosis in BD patients, which has important significance for guiding the treatment of BD.

Key words: Antiphospholipid antibody, Behcet disease, Thrombosis, Recurrence, Risk factors

中图分类号:

R593.2

李钰锴, 王红彦, 罗靓, 李云, 李春. 抗磷脂抗体在白塞病合并血栓中的临床意义[J]. 北京大学学报（医学版）, 2024, 56(6): 1036-1040.

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.

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参考文献 15

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Items	BD patients (n=222)
Age/years	41.5±13.1
Gender (female)	112 (50.5)
Thrombosis
Venous thrombosis	36 (16.2)
Arterial thrombosis	27 (12.2)
Both venous and arterial thrombosis	11 (5.0)
aCL (+)	23 (10.4)
aβ2GPI (+)	4 (1.8)
LAC (+)	29 (13.1)
Single aPL positivity	49 (22.1)
Double aPL positivity	1 (0.5)
Triple aPL positivity	3 (1.4)

Items	aPL (+) (n=49), n (%)	aPL (-) (n=173), n (%)	P value
Oral ulcers	46 (93.9)	167 (97.1)	0.288
Vulvar ulcers	21 (42.9)	106 (61.6)	0.019
Articular involvement	5 (10.2)	45 (26.0)	0.019
Neurologic involvement	6 (12.2)	24 (13.9)	0.769
Skin manifestations	13 (26.5)	62 (35.8)	0.224
Ocular involvement	9 (18.4)	47 (27.2)	0.211
Positive pathergy test	5 (16.1)	32 (30.8)	0.109
Thrombosis	22 (44.9)	29 (16.9)	< 0.001
Aneurysms	7 (14.3)	23 (13.4)	0.869
Gastrointestinal involvement	3 (6.1)	37 (21.4)	0.014

Items	aPL (+)(n=49), ${\bar x}$±s	aPL (-)(n=173), ${\bar x}$±s	P value
IgA/(g/L)	3.11±1.30	2.79±1.25	0.335
IgG/(g/L)	13.66±1.96	11.84±1.82	0.140
IgM/(g/L)	1.55±0.95	1.12±0.72	< 0.001
CRP/(mg/L)	12.97±5.17	7.49±4.22	0.010
ESR/(mm/h)	20.78±4.91	15.85±4.29	0.005
PT/s	13.75±1.89	13.01±3.24	0.931
Fib/(mg/dL)	308.26±9.76	328.72±13.99	0.538
APTT/s	33.65±2.26	32.65±5.10	0.653
FDP/(mg/L)	1.72±1.16	2.13±1.63	0.085
D-dimer/(μg/L)	182.91±14.64	256.19±21.36	0.082

Items	Univariate					Multivariate
Items	B	SE	Z	P	OR (95%CI)	B	SE	Z	P	OR (95%CI)
Age/years	0.00	0.01	-0.29	0.770	1.00 (0.97-1.02)
ESR/(mm/h)	0.00	0.01	-0.17	0.868	1.00 (0.98-1.02)
PT/s	0.20	0.08	2.45	0.014	1.22 (1.04-1.43)	0.08	0.09	0.90	0.368	1.09 (0.90-1.31)
Fib/(mg/dL)	0.00	0.00	1.34	0.182	1.00 (1.00-1.00)
APTT/s	0.00	0.01	-0.17	0.868	1.00 (0.98-1.02)
IgA/(g/L)	0.01	0.12	-0.12	0.906	0.99 (0.78-1.25)
IgG/(g/L)	0.05	0.05	0.96	0.337	1.05 (0.95-1.17)
IgM/(g/L)	0.11	0.29	0.39	0.698	1.12 (0.63-1.99)
aβ2GPI (+)	0.25	0.65	-0.39	0.700	0.78 (0.22-2.79)
aCL (+)	2.31	1.24	1.86	0.062	10.06 (0.89-114.09)
LAC (+)	2.20	0.49	4.48	< 0.001	9.06 (3.45-23.76)	2.14	0.58	3.67	< 0.001	8.51 (2.71-26.72)
HLA-B51 (+)	0.59	0.46	1.29	0.196	1.81 (0.74-4.45)
AECA (+)	0.14	0.45	-0.31	0.760	0.87 (0.36-2.11)
Aneurysm	1.05	0.46	2.29	0.022	2.85 (1.16-7.00)	0.99	0.50	1.97	0.049	2.70 (1.01-7.24)