|Budget Amount *help
¥4,400,000 (Direct Cost : ¥4,400,000)
Fiscal Year 1995 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Fiscal Year 1994 : ¥3,000,000 (Direct Cost : ¥3,000,000)
[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
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