Clinical reserch for diagnosis of immunological habitual abortion

[导言]自然流产是妊娠最常见的并发症。据估计，2%到5%的夫妇因为反复自然流产而没有孩子。(1)尽管遗传、解剖、激素因素和自身免疫性疾病已经受到影响，但仍有一部分病例无法解释。许多受此影响的夫妇都有免疫学上的原因。由于Manmmailan妊娠与母体同种异体反应的诱导和适应有关，在许多夫妇中，不适当的同种异体反应被认为是目前技术上妊娠丢失的原因之一。因此，人类白细胞抗原在夫妻间的共享性被认为是异体流产的免疫学指标。然而，最近这一指标的可靠性受到了质疑。(2)可用于诊断免疫性流产和选择最易感染的…的免疫学参数在过去的两年里，必须尽快建立更多的卵巢治疗，关注连续两次因明确原因而流产而没有活产的患者(研究组)的免疫状况，我们调查了哪些免疫学检查是预测未治愈的妇女继发妊娠预后的有用参数。[]12.7%，显著高于47例未孕健康女性(29.0=12.8%)，其中高NK活性(42.0%)定义为NK活性的平均值。在47例未孕健康女性中，24例早孕前NK活性升高的患者再次妊娠流产率(71%)明显高于44例NK活性正常的患者，后者仅有20%的妊娠丢失。相对危险度3.5；95%C11.8~6.5)(2)采用CD16和CD56两种单抗，用双色流式细胞术检测42例患者外周血中NK细胞亚群。42例中有24例再次妊娠维持正常(NP：未孕妇女)，18例早孕流产(SA：自然流产者)，NP中CD56(+)16(+)百分率，6.1()SY+。[)4.1%显著低于SA；10.2%(SY.+-)4.2%。CD56(+)16(-)和CD56(-)16(+)两组间差异有统计学意义(P&lt；0.05)。正常妊娠组CD56阳性细胞百分率为8.7%，显著低于SA组的13.7%(+-)5.3%。结果：敏感性为72.4%，快速；阳性预测值为76.9%；阳性预测值为87.5%。[讨论]反复自然流产者妊娠结局与NK细胞活性及亚群的关系清楚。人类蜕膜组织似乎在培育植入的胚胎方面发挥了重要作用，但也在防止母体免疫系统排斥它方面发挥了重要作用。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加，这些淋巴细胞和巨噬细胞影响局部免疫。在这些脱落细胞中，大颗粒淋巴细胞(LGL)在妊娠早期尤为丰富。蜕膜LGL含有大量表达NK细胞表面标志CD56的细胞。(3)还发现LGL具有NK活性。(4)由于蜕膜LGL在IL-2刺激后可杀伤人滋养层细胞，故认为蜕膜LGL在妊娠的免疫维持中起重要作用。(5)考虑到上述结果，外周血中NK细胞的分析有可能成为免疫性反复流产的有用参数。此外，我们认为NK细胞活性和NK细胞亚群这两个因素相结合可能是一个更准确的预测参数。较少

[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