Subrt Ivan, Ulcova-Gallova Zdenka, Bibkova Katarina, Micanova Zdenka, Hejnalova Marketa, Cerna Monika, Hradecky Libor, Novotny Zdenek
Institute of Medical Genetics, Department of Obstetrics and Gynecology, Charles University and Faculty Hospital, Pilsen, Czech Republic.
Am J Reprod Immunol. 2008 Mar;59(3):193-200. doi: 10.1111/j.1600-0897.2007.00554.x.
The aim of this study was to investigate frequencies of eight antiphospholipid antibodies (aPLs) in serum, four genetic thrombophilic factors and their mutual relation in 206 patients with repeated pregnancy loss (RPL).
Enzyme-linked immunosorbent assay was used for detection of aPLs against ph-serine, ph-ethanolamine, ph-inositol, DL-glycerol, phosphatidic acid, anti-annexin V, cardiolipin, and beta2-GPI. FV 1691G>A (Leiden mutation), FII 20210G>A mutation, MTHFR 677C>T and MTHFR 1298A>C variant genotypes were determined using a melting curve analysis of the PCR amplification product detected by the fluorescence resonance energy transfer. Genotypic distribution and allelic frequencies were calculated. Correlation between aPLs and thrombophilic factors was tested by chi-square and Fisher exact test.
Our results show significantly increased prevalence of aPLs against ph-inositol (17-19.6% dependent on number of spontaneous miscarriages) and against ph-serine (18-25%). aPLs in IgG prevail. In 96% of the studied group, at least one risk factor was found (either aPLs positivity or thrombophilic factor). Both aPLs and thrombophilic factors were present in 43%. In the group of women with three or more RPLs, strong positive correlation of aPLs positivity and thrombophilic risk factors was observed.
Antiphospholipide antibodies and genetic thrombophilic factors are important risk factors in the pathogenesis of RPL. Both autoantibodies against various kinds of phospholipides and genetic thrombophilic factors must be studied together in diagnosis of RPL for appropriate treatment.
本研究旨在调查206例复发性流产(RPL)患者血清中8种抗磷脂抗体(aPLs)、4种遗传性血栓形成因素的频率及其相互关系。
采用酶联免疫吸附测定法检测抗磷脂酰丝氨酸、磷脂酰乙醇胺、磷脂酰肌醇、DL-甘油、磷脂酸、抗膜联蛋白V、心磷脂和β2-糖蛋白I的aPLs。使用荧光共振能量转移检测的PCR扩增产物的熔解曲线分析来确定FV 1691G>A(莱顿突变)、FII 20210G>A突变、MTHFR 677C>T和MTHFR 1298A>C变异基因型。计算基因型分布和等位基因频率。通过卡方检验和Fisher精确检验测试aPLs与血栓形成因素之间的相关性。
我们的结果显示,抗磷脂酰肌醇的aPLs(根据自然流产次数,患病率为17%-19.6%)和抗磷脂酰丝氨酸的aPLs(患病率为18%-25%)的患病率显著增加。IgG中的aPLs占主导。在96%的研究组中,发现至少一种危险因素(aPLs阳性或血栓形成因素)。aPLs和血栓形成因素均存在的情况占43%。在有三次或更多次RPL的女性组中,观察到aPLs阳性与血栓形成危险因素之间存在强正相关。
抗磷脂抗体和遗传性血栓形成因素是RPL发病机制中的重要危险因素。在RPL的诊断中,必须同时研究针对各种磷脂的自身抗体和遗传性血栓形成因素,以便进行适当治疗。