Asymmetric Antibodies and Pregnancy

PROBLEM: Asymmetric IgG antibodies (AAb) possess a mannose-rich oligosaccharide residue bound to one of the Fab regions, making them unable to activate immunoeffector mechanisms. The proportion of asymmetric antibodies is increased after prolonged immunization with particulate antigens like cellular spleen cells. During pregnancy, AAb were found in serum and bound to placenta with specific activity to paternal antigens. No previous reports about the status of AAb in recurrent spontaneous abortion (RSA) patients have been published to date. Therefore, the aim of the present study was to analyze the percentage of asymmetric IgG molecules in serum samples of (a) healthy pregnant and non-pregnant women, (b) pregnant women with a history of RSA, and (c) non-pregnant RSA patients receiving paternal lymphocyte immunotherapy (LIT) or intravenous gammaglobulin therapy (IVIgs). METHOD OF STUDY: A previously-described differential ELISA technique was used to determine the percentage of IgG that was of the asymmetric type. RESULTS: During normal pregnancy, there was an increase in the percentage of high ConA affinity IgG serum molecules with a major increase at the second trimester. Pregnant RSA patients at the second trimester had lower values. When evaluating non-pregnant RSA patients who received LIT, it was observed that the immunized patients expressed a higher percentage of asymmetric IgG antibodies. The pregnant patients who received IVIgs had a percentage of AAbs comparable to normal pregnant patients. Additionally, the presence of IgG asymmetric molecules was confirmed in commercial gammaglobulin preparations. CONCLUSION: Results suggest a protective role of AAb during pregnancy.     

妊高征患者血清体液免疫状况与一氧化氮的相关性研究

目的　探讨患者血清体液免疫状况和一氧化氮 (NO)含量在妊高征中的作用及两者之间的相互关系 .方法　随机选择妊高征 4 9例 (妊高组 )、正常晚期妊娠 32例 (晚妊组 )、正常非孕 2 2例 (非孕组 ) ,用免疫比浊法和Greiss反应法测定血清中的免疫球蛋白 (IgA、IgG、IgM)补体 (C3 、C4)和NO .结果　晚妊组NO明显高于非孕组(p <0 .0 1) ,体液免疫各指标间无差异 (p >0 .0 5 ) ;妊高组NO较晚妊组明显下降 (p <0 .0 1) ,其下降程度与妊高征严重程度呈正比 ,体液免疫指标中IgG、IgM下降非常明显 (p <0 .0 1) ,C3 亦呈下降趋势 (p <0 .0 5 ) ;妊高组NO和IgG、IgM呈高度正相关 (p<0 .0 1) ,与C3 亦呈正相关 (p<0 .0 5 ) .结论　妊高征的发病可能与NO合成释放减少及机体体液免疫状况密切相关 ,两者相互关联、相互作用和影响着妊高征的发生和发展     

Glycation Endproducts, Soluble Receptor for Advanced Glycation Endproducts and Cytokines in Diabetic and Non-diabetic Pregnancies

Problem  Cytokines, advanced glycation end products (AGEs), and their receptor RAGE have been recently suggested to play a role in human pregnancy. In this study, we sought to determine the alterations of plasma AGEs, soluble RAGE (sRAGE), and proinflammatory cytokines in normal pregnancies and those complicated with type 1 diabetes mellitus.
Method of study  These parameters were measured in samples from healthy non-pregnant (C), diabetic non-pregnant (D), healthy pregnant (HP), and pregnant diabetic (DP) women.
Results  In the first trimester, DP showed lower sRAGE and higher AGEs compared to HP. In the DP group, significant negative correlations were seen between TNF-α and lipopolysaccharide (LPS)-stimulated ΙL-6 in the first trimester and sRAGE in the third trimester. LPS-stimulated IL-12 was positively correlated with levels of AGEs in the third trimester.
Conclusion  We detected several differences in the levels of AGEs, sRAGE, and proinflammatory cytokines between euglycemic and diabetic pregnancies.     

Aberrant cytokine production by peripheral blood mononuclear cells in recurrent pregnancy loss?

BACKGROUND: Successful pregnancy may depend on a Th2-type cytokine response, whilst, conversely, a poor pregnancy outcome may be associated with an increase in Th1 cytokines and a concomitant decrease in Th2 cytokines. This prospective study was designed to elucidate whether a failure of the cytokine shift pre-dated miscarriage and was therefore likely to be an aetiological factor in recurrent pregnancy loss (RPL). METHODS: Cytokine production by stimulated peripheral blood mononuclear cells from 46 pregnant women who had previously suffered idiopathic RPL during early pregnancy was compared with 25 gestationally age-matched pregnant controls and 11 non-pregnant women. RESULTS: Production of IFN-gamma was lower in pregnant than in non-pregnant women and even lower in RPL pregnant women (P = 0.0191). IL-10 was increased in pregnant women compared with non-pregnant controls, and further increased in RPL patients (P = 0.026). IL-4 was also increased in women with RPL (P = 0.0001). No differences in IFN-gamma, IL-10 or IL-4 secretion were observed in RPL patients who subsequently miscarried compared with those who successfully completed the pregnancy. RPL women with a successful reproductive outcome had similar concentrations of TNF-alpha to pregnant women, RPL women who subsequently miscarried had significantly lower levels than either pregnant women (P = 0.02) or non-pregnant controls (P = 0.0004). CONCLUSIONS: Contrary to our hypothesis, the cytokine shift, which appears to characterize normal pregnancy, was accentuated rather than diminished in RPL pregnant women.     

Autoantibodies in Argentine women with recurrent pregnancy loss

PROBLEM: To determine the presence or absence of subclinical autoimmunity in Caucasian Argentine healthy women with first trimester recurrent pregnancy loss (RPL), the sera of 118 healthy women with a history of three or more consecutive abortions and 125 fertile control women without abortions and two children were analyzed for the presence of autoantibodies: immunoglobulin (Ig)G and IgM anticardiolipin, antinuclear (ANA), antismooth muscle (ASMA), antimitocondrial (AMA), antiliver-kidney-microsomal fraction (LKM), antigastric parietal cells (GPC), antineutrophil cytoplasmatic (ANCA) and antibodies antigliadin type IgA and IgG and IgA antitransglutaminase related with celiac disease (CD). METHOD OF STUDY: ANA, ASMA, AMA, anti-LKM, antibodies to GPC and ANCA were determined by indirect immunofluorescence (IFI) and anticardiolipin, antigliadina and antitransglutaminase antibodies were measured by enzyme-linked immunosorbent assays (ELISA). RESULTS: There was no significant difference between controls and patients with ANA, ASMA, AMA, LKM, ANCA and GPC. The prevalence of anticardiolipin antibodies in RPL was significantly higher than controls (P < 0,01) and the prevalence of positive antibodies for antigliadina type IgA and IgG and IgA antitransglutaminase in RPL was significantly higher than controls (P < 0.04). CONCLUSION: We show that Caucasian Argentine women with RPL showed significantly higher incidence of anticardiolipin antibodies than normal controls and finally we recommended the screening of IgA and IgG antigliadina and IgA antitransglutaminase antibodies in pregnancy, because of the high prevalence of subclinical CD in RPL and the chance of reversibility through consumption of a gluten free diet.     

Peripheral blood galectin-1-expressing T and natural killer cells in normal pregnancy and preeclampsia

The purpose of this study was to determine whether the proportion of galectin-1-expressing peripheral blood T and NK cells is altered in normal pregnancy and preeclampsia (PE). We also examined whether circulating levels of galectin-1 and anti-galectin-1 autoantibodies are affected in PE. Seventy preeclamptic patients, 75 healthy pregnant and 21 healthy non-pregnant women were involved in this study. Serum galectin-1 and anti-galectin-1 autoantibody levels were measured by ELISA. Intracellular galectin-1 expression of lymphocytes was determined with flow cytometry. Serum galectin-1 and anti-galectin-1 IgG levels did not differ significantly between the healthy pregnant and the PE group. In healthy pregnant women, significantly higher percentage of T and NK cells expressed gal-1 in their cytoplasma than in healthy non-pregnant women. However, the proportion of galectin-1-expressing peripheral blood T and NK cells was markedly decreased in PE compared to normal pregnancy, which might contribute to the activation of innate and acquired immune cells.     

Polyclonal activation of IgM antibodies to phospholipids in patients with idiopathic fetal growth retardation

Phospholipid fractions and antibodies to phospholipids in the sera of normal pregnant women and patients with intra-uterine growth retardation (IUGR) were examined. Significant elevation of serum phospholipids were observed in the second and third trimesters of normal pregnancy. Serum concentration of phosphatidylserine and sphingomyelin was significantly lower in the third trimester in patients with IUGR than in normal pregnant women. Remarkable concentrations IgG and IgA antibodies to phospholipids were not observed in the patients or in normal pregnant women. Polyclonal activation of IgM antibodies was detected in normal pregnant women in the first and second trimesters but less so in the third. The activation of IgM antibodies was not observed in patients with IUGR induced by severe preeclampsia, but significant levels of IgM antibodies were detected in the third trimester in patients with idiopathic IUGR. It is suggested that antibody formation to phospholipids in normal pregnant women is induced by elevation of phospholipids and is down-regulated in the third trimester. Failure to down-regulate IgM antibodies may be related to the pathogenesis of idiopathic IUGR.     

Autoantibodies to Serum Proteins in Women with Recurrent Spontaneous Abortion: Subsequent Pregnancy Outcome

Sera from 130 first trimester pregnant women were tested for their serum antibody level against a naturally occurring serum antigen purified from non-pregnancy sera. IgG and IgM antibody level was measured using enzyme linked immunosorbant assay. Results indicate that patients with multiple abortion (n=26) have significantly (p=0.0029) lower level of IgG antibody and significantly (p=0.0001) higher level of IgM antibodies; against the serum antigen as compared to the patients with successful pregnancies with no history of miscarriage (n=63). Western blot analysis identified the scrum antigen recognized by the IgM antibody as a 24 kDa molecular mass component. These IgG and IgM antibodies may play an important role in the outcome of pregnancy.     

妊娠期妇女血浆纤维蛋白原生成和降解水平变化

目的:分析正常妊娠期妇女凝血以及纤维蛋白原生成和降解指标的变化特征,初步探讨孕妇妊娠期间的出凝血动态变化.方法:正常妊娠并顺利分娩的孕妇96例,序贯观察她们整个孕期和产后4-9周的活化部分凝血酶原时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、纤维蛋白(Fg)含量、纤维蛋白(原)降解产物(FDP)含量以及F...     

Autoantibodies to Serum Proteins in Women with Recurrent Spontaneous Abortion: Subsequent Pregnancy Outcome

Sera from 130 first trimester pregnant women were tested for their serum antibody level against a naturally occurring serum antigen purified from non-pregnancy sera. IgG and IgM antibody level was measured using enzyme linked immunosorbant assay. Results indicate that patients with multiple abortion (n=26) have significantly (p=0.0029) lower level of IgG antibody and significantly (p=0.0001) higher level of IgM antibodies; against the serum antigen as compared to the patients with successful pregnancies with no history of miscarriage (n=63). Western blot analysis identified the scrum antigen recognized by the IgM antibody as a 24 kDa molecular mass component. These IgG and IgM antibodies may play an important role in the outcome of pregnancy.     

Cellular Immunity in Normal Pregnancy and Abortion: Subpopulations of T Lymphocytes Bearing Fc Receptors for IgG and IgM

ABSTRACT: Studies on the change of peripheral T and B lymphocytes and T cells bearing Fc receptors for IgG (Ig-G?FcR⁺?T lymphocytes) and IgM (IgM?FcR⁺?T lymphocytes) in normal pregnant women and patients with threatened abortion were performed by using rosette-formation tests. There was no significant difference in the proportion of T and B lymphocytes between pregnant and nonpregnant women. The percentage change of T cells of the patients in threatened abortion with good prognosis was significantly decreased and that of B cells of the patients in threatened abortion was significantly increased compared with that of normal pregnant women. The percentage of IgG?FcR⁺?T lymphocytes in the T lymphocytes increased in the various stages of pregnant and postpartum women as compared with that in nonpregnant women, and in the case of the patients with threatened abortion it also increased significantly from that of normal pregnant women. On the contrary, the percentage of IgM?FcR⁺?T in the T lymphocytes decreased in normal pregnant and postpartum women.     

Antinuclear autoantibodies in healthy nonpregnant and pregnant women and their offspring.

Antinuclear autoantibodies have previously been detected in sera of healthy women although less frequently than in sera of women with autoimmune disorders. The effect of pregnancy on antinuclear autoantibody production in healthy women is as yet debatable. We present four studies in which, by employing the ELISA method, we evaluated the presence of six antinuclear autoantibodies (anti-ds DNA, anti-ss DNA, anti-poly(I), anti-cardiolipin, anti-Sm, and anti-RNP) in the sera of more than 1,000 healthy pregnant and nonpregnant women, including 196 pairs of matched maternal and cord blood sera. In all four studies healthy pregnant women did not demonstrate significantly higher prevalence rates of various serum antinuclear autoantibodies as compared to healthy non-pregnant women. All detected autoantibodies were of the IgM isotype. In only one infant (born to a healthy seronegative mother) was an autoantibody (IgM anti-ss DNA) detected. This may indicate that in certain circumstances the fetus is capable of self-production of autoantibodies.     

Cellular immunity in pregnancy: subpopulations of T lymphocytes bearing Fc receptors for IgG and IgM in pregnant women.

Studies on the change of peripheral T and B lymphocytes and T cells bearing Fc receptors for IgG and IgM in pregnant women were performed by using rosette-formation tests. There was no significant difference in the proportion of T and B lymphocytes between pregnant and non-pregnant women. The percentage of T cells bearing Fc receptors for IgG in the T lymphocytes which are considered to have suppressive activity increased in the various stages of pregnancy and post-partum as compared with that in non-pregnant women. On the contrary, the percentage of T cells bearing Fc receptors for IgM in the T lymphocytes which have a helper function decreased in pregnant and post-partum women. The results of this investigation suggest that the depression of cell-mediated immunity during pregnancy depends on the qualitative change of T lymphocytes, i.e. increased suppressor and decreased helper T lymphocyte subpopulations.     

Prevalence of hypothyroidism in recurrent pregnancy loss in first trimester

Aim: To determine the frequency of hypothyroidism in women with recurrent pregnancy loss in first trimester in the Indian population. Settings and Design: The study included 163 non-pregnant women with recurrent pregnancy loss in a gestational age up to 相似文献   

1141605463Autoimmune and thrombophilic causes of recurrent pregnancy loss in greek couples

Introduction:  This was a retrospective study performed in order to investigate the distribution of various autoimmune and thrombophilic causes including gene mutations in the Greek population that have been associated in the literature with recurrent pregnancy loss (RPL), the latter considered after at least two and not three fisrt trimester embryo losses.
Materials and Methods:  We included in this study the last 80 couples that entered our Recurrent Pregnancy Unit which had at least two consecutive miscarriages before the 13th week of gestation with no other pregnancy apart from induced abortions. They had been checked for: phospholipid autoimmunity (anticardiolipins, β2GPI and serine antiphoSPSholipid antibodies (IgG and IgM)), ANA, antithyroid antibodies (AA), immunoglobulins (IgG, IgA and IgM) and for thrombophilia incuding protein C, protein S, activated protein C resistance (APC-R), antithrombin III, homocystein, lupus anticoagulant and the following gene mutations: FVLeiden, Prothrombin 20210A, MTHFR T677T (homozygous or double heterozygous for C677T and A1298C), PAI-1 4G/5G and the GPI-α gene mutation.
Results:  At least one thrombophilic factor was found in 19 patients (24%), an autoimmune factor in 7 (9%), ANA (+) >1/160 in 14 (17%), AA in 19 (25%), increased IgG in 5 (62%). 11 had a possible anatomic factor (18%). Five out of the 19 patients (26%) with thrombophilia had a thrombophilic gene mutation with no phenotypic findings in peripheral blood. All percentages were calculated with respect to the number of patients searched for the specific factor.
Conclusion:  The distribution of the above factors is discussed and their possible role in RPL. The high percentage of thrombophilia gene mutations among patients with a thrombophilic factor is mainly discussed as well as the need to include those expensive tests in the work-up of RPL.     

Gestational Age-specific Cut-off Values Are Needed for Diagnosis of Subclinical Hypothyroidism in Early Pregnancy

During the first trimester of pregnancy, thyroid-stimulating hormone (TSH) >2.5 mIU/L has been suggested as the universal criterion for subclinical hypothyroidism. However, TSH levels change continuously during pregnancy, even in the first trimester. Therefore the use of a fixed cut-off value for TSH may result in a different diagnosis rate of subclinical hypothyroidism according to gestational age. The objective of this study was to obtain the normal reference range of TSH during the first trimester in Korean gravida and to determine the diagnosis rate of subclinical hypothyroidism using the fixed cut-off value (TSH >2.5 mIU/L). The study population consisted of pregnant women who were measured for TSH during the first trimester of pregnancy (n=492) and nonpregnant women (n=984). Median concentration of TSH in pregnant women was lower than in non-pregnant women. There was a continuous decrease of median TSH concentration during the first trimester of pregnancy (median TSH concentration: 1.82 mIU/L for 3+0 to 6+6 weeks; 1.53 mIU/L for 7+0 to 7+6 weeks; and 1.05 mIU/L for 8+0 to 13+6 weeks). Using the fixed cut-off value of TSH >2.5 mIU/L, the diagnosis rate of subclinical hypothyroidism decreased significantly according to the gestational age (GA) at TSH (25% in 3+0 to 6+6 weeks, 13% in 7+0 to 7+6 weeks, and 9% for 8+0 to 13+6 weeks, P<0.001), whereas the diagnosis rate was 5% in all GA with the use of a GA-specific cut-off value (P=0.995). Therefore, GA-specific criteria might be more appropriate for the diagnosis of subclinical hypothyroidism.     

Changes in the expression of nitric oxide synthase in the human uterine cervix during pregnancy and parturition

Nitric oxide (NO) has been proposed as a mediator of cervical ripening. We investigated the expression, using Western blotting, and localization, using immunohistochemistry, of the nitric oxide synthase (NOS) enzymes, inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal NOS (bNOS) in the human cervix during pregnancy and parturition. Cervical biopsies were obtained from non-pregnant women, women in the first trimester of pregnancy, and pregnant women at term before and after the onset of labour. Each of the NOS isoforms was localized in the cervices of both non-pregnant and pregnant subjects using immunohistochemistry. iNOS expression was significantly greater in early pregnancy compared with the non-pregnant state (P: < 0.005). iNOS expression was up-regulated further in samples obtained in the third trimester compared with the first trimester. bNOS expression was greater in samples from the first trimester of pregnancy than in non-pregnant samples (P: < 0. 005), but showed no additional increase in late pregnancy or with the onset of labour. eNOS expression was increased in samples obtained in the third trimester both before (P: = 0.002) and after the onset of labour (P: < 0.002) when compared with non-pregnant samples. The increased expression of NOS isoforms in late pregnancy supports the hypothesis that NO is involved in the process of cervical ripening.     

孕前及孕期妇女风疹免疫力调查和风疹近期感染检测

目的了解孕前妇女及孕期妇女风疹易感水平和近期感染状况，为预防先天风疹感染做好优生优育工作提供依据。方法用生物蛋白芯片技术对2986例孕前妇女及863例孕期妇女（包括725例正常妊娠和138例异常妊娠）进行风疹特异性抗体IgM、IgG检测。结果80．27％的孕前妇女具有免疫力，4．99％孕前妇女为风疹近期感染，14．03％妇女对风疹易感。89．00％的孕期妇女具有免疫力，1．96％孕期妇女为风疹近期感染，7．76％妇女对风疹易感。孕前妇女及孕期妇女的风疹近期感染率和易感率比较有显著性差异（χ^2=14．797、23．846，P〈0．001）；不良妊娠与正常妊娠之间风疹近期感染率和易感率比较有显著性差异（X。=30．635、4．174，P〈0．05）；市区与农村的孕前妇女及孕期妇女在风疹近期感染率和易感率比较无明显不同；孕前妇女及孕期妇女风疹近期感染月份分布均以5月最高。结论本地区孕前妇女风疹感染率高；风疹感染与不良妊娠密切相关：市区与农村妇女的风疹易感水平和近期感染状况相当。对孕前妇女及孕期妇女同时检测风疹特异性抗体IgM、IgG可以正确判定妇女的免疫状况，有效预防、主动发现并合理处理孕妇感染，从而降低风疹感染率提高优生优育水平。     

Haematological Changes During Normal Pregnancy in New Zealand White Rabbits: A Longitudinal Study

The present study was undertaken to investigate changes in haematology parameters over the course of normal pregnancy in New Zealand White rabbits. Blood samples were collected on gestational days (GD) 0, 4, 8, 12, 16, 20, 24, and 28. Red blood cell counts and haemoglobin concentrations on GD 20–28 were lower than those of normal non-pregnant rabbits. These values fluctuated slightly between GD 0 and 12 and subsequently decreased to reach a nadir on either GD 24 or 28. Haematocrit value in pregnant rabbits also decreased slightly in the third trimester, but the difference was not statistically noticeable. Mean corpuscular volume in pregnant rabbits increased gradually during the course of gestation and was larger on GD 24 than that in non-pregnant rabbits. There were no differences in mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration between pregnant and non-pregnant rabbits. Platelet counts on GD 24–28 were lower than that of normal non-pregnant rabbits. These values increased slightly in the first half of gestation and then decreased to reach a nadir on GD 28. Total white blood cell and lymphocyte counts on GD 24 were lower than those of normal non-pregnant rabbits. These values increased maximally by GD 4 and then decreased progressively to a minimum level on GD 24. No significant differences were observed in the numbers of neutrophils, eosinophils, basophils, and monocytes between pregnant and non-pregnant rabbits. Neutrophil counts of pregnant rabbits fluctuated minimally between GD 0 and 12 and then decreased to reach a lowest level on GD 24. Eosinophil counts increased to a maximum value on GD 4 and subsequently decreased to reach a nadir on GD 24. Basophil and monocyte counts were not different throughout the course of pregnancy. These data can be used not only as a historical database for the effective evaluation of data from reproductive toxicology studies, but also as a contribution to biological characterization of New Zealand White rabbits.