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Clinical reserch for diagnosis of immunological habitual abortion

免疫性习惯性流产诊断的临床研究

基本信息

批准号：
06454478
负责人：
YAGAMI Yoshiaki
金额：
$ 2.82万
依托单位：
Nagoya City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

[Introduction] Spontaneous abortion is the most complication of pregnancy. Estimates show that 2% to 5% couple me childless because of repeated spontaneous abortion. (1) Although genetic, anatomic, hormonal factors, and autoimmune disorders have been impticated, a substatial proportion of cases remain unexplained. An immunological cause has been suggested for many such affeted couples. Because manmmailan pregnancy is associated with the induction and adaptation of maternal allogeneic reactions, inappropriate allogenic responses have been suggested as a cause of tecurrent pregnancy loss in many coupies. The sharing of HLA antlgens between husband and wife has thus fur been considered as an immunological indicator of habltual abortion due to inappropriate allogenic response. However, recently, the rellability of this indicator has been thrown into doubt. (2) Therefore, immunological parameter that could be used to diagnose immunological abortion and seiect the most sultable form of immun … More otherapy must be estabilshed as soon as possible During the past two years, concentrating attentions on the immunological status of patients who had histories of two consecutive first-trimester abortions due to euexpiained cause and no live births (study group), We have investigated which immunological tests were useful predictive parameter for prognosis of subsequent pregnancy in women who had had recelved no tratment.[Resuits] (1) NK (natual killer) -cell activity (mensured by a chromium-51 release cytotoxic assay, with K562 human myeloid leukemia cells as targets) in 68 patients of the study group was 39.4(]SY.+-。[)12.7%, significant higher than that of 47 non-pregnant healthy females with no history (29.0=12.8%) With a high level of NK activity (42.0%) defined as the mean pius 1 SD of NK activity in 47 non-pregnant healthy females, the 24 patients with raised preconceptional levels of NK activity had a much higher abortion rate (71%) in the subsequent pregnancy than the 44 patlents with normal NK activity, who experlenced pregnancy loss in only 20% of pregnancles. (relative risk 3.5 ; 95% C11.8-6.5)(2) NK subsets in pripheral blood lymphpcytes were identifled by two-color flow cytometry using two monoclonal antibody ; CD 16 and CD56 in 42 patients of the study group. The 24 patients of 42 maintained the next pregnancy normally (NP : notnal prenant women ) The 18 patients of 42 aborted in the first trimester (SA : spontaneous aborters) The percentage of CD56 (+) 16 (+) in NP ; 6.1(]SY.+-。[)4.1% was significant lower compared with that in SA ; 10.2%(]SY.+-[)4.2%. (p<0.05) In other subsets ; CD56 (+) 16 (-) and CD56 (-) 16 (+), there were significant differenes between the two groups. The percentage of CD56-positive cells in NP was 8.7(]SY.+-[)4.3%, significant lower than 13.7%(]SY.+-[)5.3% in SA.Frequency of CD56-positive cells >=12.5% between viableand and nonviable pregnacy was checked out. The results were sensitivity : 72.4%, spedificity ; 76.9% positive predictive value ; 87.5%.[Discussion] The associations between pregnancy outcome of the recurrent spontaneous aborters and NK cells : activity and subsets were revealed clearly. Human decidual tissue appears to play an important role in nurturing the implanted emgryo, but also in preventing its rejection by the maternal lmmune system. Compared with the uterine endometrium, eariy decidual tissue has been shown to contain a markedly increased number of various kinds of lymphocytes and macrophages, which afect local lmmunlty. Among these decldual cells, the large granular lymphocytes (LGL) are especially abundant in the first trimester of pregnancy. Decidual LGL contain many cells expressing CD56, a surface marker of NK cells. (3) Moreover, decldual LGL have been revealed NK activity. (4) Since additionally decidual LGL could kill human trophoblasts cells after prior stimulation with interleukin-2, it is considered that decidual LGL play a pivotal role in the immunological maintenance of pregnancy. (5) Considering the above results, it is considered as possible that the analysis of NK cells in the peripheral blood leveis might be useful parameter for immunological recurrent abortion. Additionally.we supposed that the combination of two factors, NK activity and NK subset, could be a more accurate predictive parameters. Less

自然流产是妊娠期最常见的并发症。据估计，2%至5%的夫妇因为反复自然流产而没有孩子。(1)虽然遗传、解剖、激素因素和自身免疫性疾病已被发现，但仍有相当一部分病例无法解释。许多这样的夫妻被认为是免疫学上的原因。由于曼氏妊娠与母体同种异体反应的诱导和适应有关，因此不适当的同种异体反应被认为是许多夫妇当前妊娠丢失的原因。因此，夫妻间HLA抗原的共享被认为是由于不适当的同种异体反应而导致的人工流产的免疫学指标。然而，最近，这一指标的可靠性受到了质疑。(2)因此，免疫学参数可作为诊断免疫性流产和选择最佳免疫形式的指标 ...更多信息在过去的两年里，我们集中注意力于有两次连续的早期妊娠流产史和无活产的患者（研究组）的免疫状态，以探讨哪些免疫学检查是未接受治疗的妇女再次妊娠预后的有用预测参数。[结果]（1）研究组68例患者的NK细胞活性（以K562人髓系白血病细胞为靶细胞，采用~（51）Cr释放细胞毒试验测定）为39.4 ± 0.01（SY）。[] 12.7%，显著高于47例无妊娠史的健康女性（29.0=12.8%）NK活性高（42.0%）定义为47名未妊娠健康女性的NK活性平均值加1 SD，孕前NK活性升高的24例患者再次妊娠流产率（71%）明显高于NK活性正常的44例患者，只有20%的孕妇流产。（相对危险度3.5 ; 95% C11.8-6.5）（2）采用流式细胞术检测42例患者外周血淋巴细胞中的NK细胞亚群。42例中24例正常妊娠（NP：未孕妇女），18例早期流产（SA：自然流产者）。[)4.1 10.2%（]SY. ±- [)4.2%.（p<0.05）其它亚群：CD 56（+）16（-）和CD 56（-）16（+）在两组间差异有显著性。NP中CD 56阳性细胞的百分比为8.7（± SD）。[)4.3%，显著低于13.7%（± SD. ± SD. [)5.3在活细胞和非活细胞中，CD_（56）阳性细胞的频率>=12.5%。结果：敏感性72.4%，特异性76.9%，阳性预测值87.5%。[讨论]明确了自然流产患者的妊娠结局与NK细胞活性及亚群的关系。人类的蜕膜组织在滋养植入的胚胎方面起着重要的作用，而且在防止母体免疫系统对其的排斥方面也起着重要的作用。与子宫内膜相比，早期蜕膜组织中各种淋巴细胞和巨噬细胞的数量明显增多，影响局部免疫功能。在这些细胞中，大颗粒淋巴细胞（LGL）在妊娠早期尤为丰富。蜕膜LGL含有许多表达NK细胞表面标志物CD 56的细胞。(3)此外，还发现了LGL的NK活性下降。(4)由于在预先用白细胞介素-2刺激后，另外的蜕膜LGL可以杀死人滋养层细胞，因此认为蜕膜LGL在妊娠的免疫维持中起关键作用。(5)以上结果提示，外周血NK细胞检测有可能成为免疫性复发性流产的一个有用指标。另外，我们认为NK细胞活性和NK细胞亚群这两个因素的结合可能是一个更准确的预测参数。少