不育症の病態 : その免疫学的考察

NDLデジタルコレクション NDLデジタルコレクション

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  • Pathogenesis on Infertility : Its Immunological Aspects

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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 enzime-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 mi ght 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-pisitive 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. 3. Activity of natural killer cells in the presence of monocytes. 4. Quantitative and qualitative change in suppressor T cells. 5. Analysis of macrophage function in the decidua. 6. M-CSF (macrophage-colony stimulating factor) level in the serum. Based on the results of the above evaluations, it can be summarized that the major immunological mechanisms responsible for successful maintenance of pregnancy consist of 3 components, that is, production of blocking factors, reduction of cellular-immunity and formation of cytokine-network, induced by maternal reactivity against alloantigens. When there is a lack of maternal immunological reactivity, infertility might be considered to result from impairment of immunological mechanisms. Immunotherapeutic approaches have been developed in order to improve the lack of maternal immunological reactivity, allowing achievement of about 80% live birth rate. The sharing of HLA antigens between husband and wife has been used as an immunological indicator in the immunothera peutic options up to now. However, recently, the rel

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