IMMUNOLOGICAL RESEARCH ON THE PATHOGENESIS OF PREECLAMPSIA AND THE PREDICTION OF ITS MANIFESTATION.

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We have investigated the relationship between the pathogenesis of preeclampsia and human leukocyte antigen (HLA)-G which is thought to play an important role in maintaining pregnancy. First, we have established and enzyme-linked immunosorbent assay (ELISA) system to measure soluble HLA-G protein (Ref 1). Secondly, in regard to the fact that the expression of HLA-G on trophoblasts is attenuated and interleukin (IL)-2 is aberrantly expressed in decidual tissue in preeclamtic placenta, we analyzed the growth of HLA-G-negative and -positive trophoblast cell line in the culture with or without IL-2 supplementation. We found that the expression of HLA-G on trophoblastic cell line completely eliminated the growth-inhibitory effect of IL-2, which might be relevant to maternal tolerance of the fetus during pregnancy and its derangement as exemplified by preeclampsia (Ref 2). Thirdly, we found that upon the contact with HLA-G, the amounts of T helper 1 (Th1) cytokines released from decidual mono … More nuclear cells and peripheral blood monon clear cells (PBMCs) were decreased, while the amounts of T helper 2 (Th2) cytokine from PBMCs was increased with Th2 cytokine release from decidual mononuclear cells being unchanged (Ref 3).We then investigated the pathogenesis of recurrent abortion and the mechanism of its immunotherapy using paternal mononuclear cells because as well as preeclampsia, the derangement of feto-maternal immune reaction is thought to play an important role in the pathogenesis of recurrent abortion. First, we found that HLA-G allelic abnormality seemed to have little, if any, implication in the pathogenesis of recurrent abortion (Ref 4). Secondly, the immunotherapy for recurrent aborters did not affect the expression of natural killer (NK) receptors regardless of the outcome of subsequent pregnancies, suggesting that recurrent aborters may benefit from the immunotherapy through mechanisms unrelated to alteration in NK receptor status (Ref 5). Thirdly, to gent insight into the basis for the empirical usage of herbal medicines in the treatment of recurrent abortion, we examined whether Tokishakuyaku-san (Toki) and Sairei-to (Sai) modulate Th1 and Th2 cytokine release from PBMCs. Toki and Sai increased the release of Th1 cytokines, which may have therapeutic potential particularly in autoimmunity -related recurrent abortion where Th2 response is pathologically enhanced (Ref 6,7). Less