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[不孕症的发病机制;其免疫学方面]

[Pathogenesis on infertility; its immunological aspects].

作者信息

Yagami Y

机构信息

Department of Obstetrics and Gynecology, Nagoya City University Medical School.

出版信息

Nihon Sanka Fujinka Gakkai Zasshi. 1993 Aug;45(8):735-47.

PMID:8371005
Abstract

Infertility is defined as a reproductive disorder in which pregnancy is established, but normal fetal growth can never be achieved due to pregnancy loss. The pathogenesis of this disorder must be understood accurately to obtain optimal results in its management. Although genetic, anatomic and hormonal factors have been implicated as to its cause, a substantial proportion of cases remain unexplained. Recently, an immunologic etiology for this disorder has been proposed for many couples with infertility due to unexplained causes. Author has evaluated patients with infertility according to two immunologic aspects, namely "autoimmune" and "alloimmune", and assessed them pathophysiologically and clinically. [Autoimmune abnormality] Autoimmune diseases, especially SLE, have been associated with pregnancy loss, with autoantibody abnormalities being speculated to be causally related to this reproductive disorder. Especially among various autoantibodies, author noticed an antiphospholipid antibody (aPL) that has been associated with micro-thrombosis, and performed the enzyme-linked immunosorbent assay. Pathophysiological evaluations performed were as follows: 1. Inhibitory effect of aPL on prostacyclin production in cultured vascular endothelial cells. 2. Existence of aPL in the elute from placental tissue. Clinical evaluations were as follows: 1. Frequency of aPL positivity among patients with infertility. 2. Correlation between frequency of aPL positivity at the placental site and the outcome of pregnancy. 3. Correlation between the selected modes of medical therapy (e.g., administration of prednisolone, aspirin, etc.) in aPL-positive cases and the outcome of pregnancy. Based on the results of the above evaluations, it was suggested that IgG-aPL can be considered a useful diagnostic and prognostic variable in women with infertility. Moreover, it was considered that the inhibition of prostacyclin production due to aPL might disturb utero-placental circulation by vasoconstriction and local vascular thrombosis in the placenta and thus lead to pregnancy loss. It was confirmed that the combination of immunosuppressive and anticoagulant therapy is, to a certain extent, an effective treatment for aPL-positive pregnant women. [Alloimmune abnormality] When normal pregnancy is viewed from an immunological standpoint, there arises a basic question of how the fetus escapes immunological rejection despite being allograft. Explanations have been based on various mechanisms of maternal immunity and some experiments were therefore attempted to elucidate the immunological mechanisms. Points of evaluation were as follows: 1. Blocking activity of serum utilizing the mixed lymphocyte reaction with lymphocytes of the husband as stimulators and those of the wife as responders. 2. Detection of HLA-class II antibody, cold-B cell antibody, and anti-idiotype antibody as blocking antibodies in the serum.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

不孕症被定义为一种生殖障碍,即虽已受孕,但由于妊娠丢失而无法实现正常的胎儿生长。必须准确了解这种疾病的发病机制,以便在其治疗中获得最佳效果。尽管遗传、解剖和激素因素被认为与病因有关,但仍有相当一部分病例原因不明。最近,对于许多不明原因不孕的夫妇,有人提出这种疾病存在免疫病因。作者根据“自身免疫”和“同种免疫”这两个免疫方面对不孕症患者进行了评估,并从病理生理学和临床角度对他们进行了评估。[自身免疫异常]自身免疫性疾病,尤其是系统性红斑狼疮,与妊娠丢失有关,推测自身抗体异常与这种生殖障碍存在因果关系。在各种自身抗体中,作者特别注意到一种与微血栓形成有关的抗磷脂抗体(aPL),并进行了酶联免疫吸附测定。进行的病理生理学评估如下:1. aPL对培养的血管内皮细胞中前列环素产生的抑制作用。2. 胎盘组织洗脱液中aPL的存在情况。临床评估如下:1. 不孕症患者中aPL阳性的频率。2. 胎盘部位aPL阳性频率与妊娠结局之间的相关性。3. aPL阳性病例中所选治疗方式(如泼尼松龙、阿司匹林等的给药)与妊娠结局之间的相关性。根据上述评估结果,提示IgG-aPL可被视为不孕症女性有用的诊断和预后变量。此外,认为aPL导致的前列环素产生抑制可能通过胎盘血管收缩和局部血管血栓形成扰乱子宫胎盘循环,从而导致妊娠丢失。已证实免疫抑制和抗凝治疗的联合在一定程度上是aPL阳性孕妇的有效治疗方法。[同种免疫异常]从免疫学角度看待正常妊娠时,会出现一个基本问题,即胎儿作为同种异体移植物如何逃避免疫排斥。对此的解释基于母体免疫的各种机制,因此进行了一些实验以阐明免疫机制。评估要点如下:1. 以丈夫淋巴细胞为刺激细胞、妻子淋巴细胞为反应细胞,利用混合淋巴细胞反应检测血清的阻断活性。2. 检测血清中作为阻断抗体的HLA-II类抗体、冷B细胞抗体和抗独特型抗体。(摘要截断于400字)

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