Anaphylaxis as a physiological mechanism of masking of embryonic antigens

It is known that anaphylactic mediators induce blood-coagulation, which results in thrombus-formation in the place of the anaphylactic reaction. This thrombus is likely to mask the antigen which induced the anaphylaxis, thus protecting it from further immune effect. The fact that only higher mammals have IgE-antibodies, exclusively high content of mast cells in the uterus, degranulation of placental mast cells near the embryonic tissue, presence of “fibrinoid” on the mother-embryo frontier and other known facts enable us to suppose that anaphylaxis is a physiological mechanism which protects the embryo from damage by the maternal immune system.     

Presentation of antigen by human newborn monocytes to maternal tetanus toxoid-specific T-cell blasts

The requirement for linked HLA-D antigen recognition for the proliferation of antigen-specific T-cell blasts provides a method for testing antigen presentation of human monocytes. We used maternal tetanus toxoid-specific T-cell blasts to show that human newborn monocytes can process and present antigen at least as well as maternal monocytes. These results suggest that human monocytes are relatively more mature at birth than those of newborn rats and mice. A major role for monocyte-macrophage immaturity in limiting the immune responses of human newborns is therefore unlikely.     

Kinetics of decline of maternal measles virus-neutralizing antibodies in sera of infants in France in 2006

The optimal age for measles vaccination is an important health issue, since maternal antibodies may neutralize the vaccine antigen before a specific immune response develops, while delaying vaccination may increase the risk of complicated diseases in infants. However, measles vaccination impacts the duration of protection afforded by transplacental transfer of maternal antibodies: vaccination-induced maternal antibodies disappear faster than disease-induced antibodies. In order to maintain protection against measles in infants, it is important to monitor the dynamics of this phenomenon in vaccinated populations. To assess the current situation in France, a multicenter, prospective seroepidemiological study was conducted in seven French hospitals between October 2005 and January 2007. Maternal measles antibody concentrations from 348 infants 0 to 15 months old were measured using the plaque reduction neutralization assay. Geometric mean concentrations and the percentage of infants with maternal measles antibody concentrations above the protection threshold (≥120 mIU/ml) were assessed according to age. Results show that after more than 20 years of routine measles vaccination in France, maternal measles-neutralizing antibodies decrease dramatically in French infants by 6 months of age, from 1,740 mIU/ml for infants 0 to 1 month old to 223 mIU/ml for infants 5 to 6 months old, and that 90% of infants are not protected against measles after 6 months of age. Infant protection against measles could be optimized both by increasing herd immunity through an increased vaccine coverage and by lowering the age of routine vaccination from 12 to 9 months.     

Immune responses to the R4 protein antigen of group B streptococci and its relationship to other streptococcal R4 proteins.

The R antigen, a trypsin-resistant protein observed in group A, C, F, G, and L streptococci, has also been found in group B streptococci (GBS). Although four species of the R antigen have been described for GBS, the R4 protein is the most prevalent in GBS isolates recovered from humans. This study examined the prevalence of antibodies against the R4 antigen by Western blot (immunoblot) (WB) in sera from 40 mothers colonized with GBS serotype II and III and from 26 noncolonized mothers; 92.5% of the colonized mothers had anti-R4 antibodies, compared with 54% of the noncolonized mothers (P < 0.001). Findings of antibodies in neonatal cord sera (n = 14) were concordant with maternal results by WB analysis for 71% of mother-infant pairs colonized with serotype II and for 57% of pairs colonized with serotype III. Of mothers known to be colonized with type II/R4 or III/R4, 100% (n = 12) had antibody against R4 by WB. This study also evaluated the prevalence of antibody to the GBS R4 antigen in 48 sera from individuals with high and low group A streptococcal anti-DNase B titers. Of those individuals with an anti-DNase B titer of > 640, 64% had a positive WB for anti-R4 antibody, compared with 30% of individuals with low anti-DNase B titers (P < 0.05). The R4 antigen of GBS had immunologic identity to the R4 antigen of group A streptococci. Overall, the findings suggested that antibodies to the streptococcal R4 antigen were commonly present in GBS-colonized mothers and that transplacental passage of these antibodies occurred. The presence of antibody to R4 in non-GBS-colonized individuals may be due to immunologic responses to past exposure to the R antigen present in GBS or other streptococcal groups.     

Diagnosis of Penicillium marneffei Infection by Quantitation of Urinary Antigen by Using an Enzyme Immunoassay

Penicillium marneffei is a major cause of opportunistic infection in patients with AIDS in north and northeastern Thailand. A method for the quantitation of P. marneffei antigen in urine was developed by using fluorescein isothiocyanate-labelled purified rabbit hyperimmune immunoglobulin G in an enzyme-linked immunosorbent assay. This method was evaluated with 33 patients with culture-proven penicilliosis and 300 controls (52 healthy subjects, 248 hospitalized patients without penicilliosis) from the same area in which penicilliosis is endemic. Urinary antigen was found in all 33 (100%) patients with penicilliosis, with a median titer of 1:20,480. With undiluted samples, 67 (27%) of 248 hospital patients and 3 (6%) of 52 healthy controls were reactive. At a cutoff titer of 1:40, the urine antigen detection assay had a diagnostic sensitivity of 97% and specificity of 98% (positive predictive value, 84%; negative predictive value, 99.7%). This test offers a valuable and rapid method for the diagnosis of penicilliosis in patients with AIDS and could be a useful addition to conventional diagnostic methods in areas in which penicilliosis is endemic.     

Mode of Inheritance of HLA Haplotypes Locus A,B in Siblings of Different Sexes

METHOD: Forty-eight parents and 172 children were typed for class I HLA antigens, locus A,B. RESULTS: Although the number of cases is small, we observed: (1) a significantly decreased number of sons born after a first delivery of a son, as compared to a first delivery of a daughter; (2) significantly increased sharing of maternal class I HLA antigens between the firstborn son and his brothers from higher birth orders, as compared to his sisters; and (3) HLA-A2 antigen, which is known to be involved in HLA restricted cytotoxic reactions in the recognition of minor histocompatibility antigens, was inherited in subsequent deliveries of sons as compared to daughters in a significantly higher frequency from the paternal than from maternal HLA haplotype. The results suggest that sharing of identical maternal HLA haplotypes between brothers may aid to decrease the degree of maternal sensitization to fetal antigens, and lack of HLA-2 antigen in maternal cells from sons as compared to daughters may avoid maternal HLA-A2 restricted cytotoxic reactions toward the male fetus.     

Relationship among maternal blood lead,ALAD gene polymorphism and neonatal neurobehavioral development

Lead is a widely used heavy metal that can affect children’s nervous system development. ALAD gene polymorphism is associated with lead neurotoxicity. This study aimed to clarify the relationship among maternal blood lead, ALAD gene polymorphism, and neonatal neurobehavioral development through detecting maternal blood lead and ALAD gene polymorphism. 198 maternal and neonatal were selected as the research object. Graphite furnace atomic absorption method was applied to detect the maternal blood lead concentration. PCR-RFLP was used to detect ALAD genotype distribution. Neonatal NANB score was treated as effect indicator. SPSS was used for statistical analysis. The ALAD genotype was 181 cases (91.4%) for ALAD₁₁ and 17 cases (8.6%) for ALAD₁₂. ALAD allele frequency distribution accords with genetics Hardy-Weinberg balance (P > 0.05). Blood lead level in maternal with ALAD₁₂ genotype was significantly higher than with ALAD₁₁ genotype (P < 0.01). NANB score in high blood lead neonatal group was obviously lower than the low blood lead group (P < 0.05). Newborn’s NANB score from the maternal with ALAD₁₁ genotype was lower than from the maternal with ALAD₁₂ genotype (P < 0.01). After ruling out the confounding factors influence by multiple linear regressions, ALAD gene polymorphisms had no significant correlation with neonatal NANB score (P > 0.05). ALAD gene polymorphism is associated with the blood lead level. Low level lead exposure in utero may cause newborn early neurobehavioral maldevelopment. Maternal ALAD gene polymorphism can affect early neonatal neurobehavioral development by influencing the blood lead level.     

Next generation sequencing of SNPs for non-invasive prenatal diagnosis: challenges and feasibility as illustrated by an application to β-thalassaemia

β-Thalassaemia is one of the most common autosomal recessive single-gene disorder worldwide, with a carrier frequency of 12% in Cyprus. Prenatal tests for at risk pregnancies use invasive methods and development of a non-invasive prenatal diagnostic (NIPD) method is of paramount importance to prevent unnecessary risks inherent to invasive methods. Here, we describe such a method by assessing a modified version of next generation sequencing (NGS) using the Illumina platform, called ‘targeted sequencing'', based on the detection of paternally inherited fetal alleles in maternal plasma. We selected four single-nucleotide polymorphisms (SNPs) located in the β-globin locus with a high degree of heterozygosity in the Cypriot population. Spiked genomic samples were used to determine the specificity of the platform. We could detect the minor alleles in the expected ratio, showing the specificity of the platform. We then developed a multiplexed format for the selected SNPs and analysed ten maternal plasma samples from pregnancies at risk. The presence or absence of the paternal mutant allele was correctly determined in 27 out of 34 samples analysed. With haplotype analysis, NIPD was possible on eight out of ten families. This is the first study carried out for the NIPD of β-thalassaemia using targeted NGS and haplotype analysis. Preliminary results show that NGS is effective in detecting paternally inherited alleles in the maternal plasma.     

Association Between Maternal-Fetal HLA-DR Relationships and Fetal Growth

PROBLEM: To determine whether maternal-fetal human leukocyte antigen (HLA) antigenic relationships are associated with differential fetal growth in weight. METHOD: A cohort of 659 primigravid women were enrolled in this study in the prepartum period and their neonates were subsequently examined. Anthropometric, maternal cigarette smoking behavior, health, pregnancy, and delivery data were collected; serogenetic typing was conducted on maternal and cord bloods to determine maternal and neonatal HLA antigenic phenotypes. Women and their neonates were assigned to one of the four different types of maternal-fetal relationships existing at each of the HLA-A, B, DR, and DQ loci. Birthweights were treated quantitatively and qualitatively (neonates classified as growth-retarded or normal). RESULTS: After controlling for other factors influencing birthweight (e.g., smoking, maternal body size), significantly lower birthweight trends (P < .01) were found when neonates expressed a single HLA-DR antigen and their mothers expressed a second HLA-DR antigen that was foreign (allogeneic) to their neonate. CONCLUSION: Our finding supports the hypothesis that lack of maternal immune exposure to fetal HLA antigens is associated with a slowing of fetal growth. However, in this situation slowed fetal growth is most likely to occur when the fetus is potentially exposed to maternal HLA-DR alloantigens. We believe this sheds new light on immunologic events at the maternal-fetal interface influencing fetal growth. We present one possible explanation to account for this finding.     

The effects of maternal haemoglobin as an indicator of maternal nutritional status on,maternal measles antibodies of mother-infant pairs at birth

Background

Maternal measles antibodies (MMA) are actively transferred through the placenta from mother to foetus. A relationship could exist between MMA of mother-infant pairs and maternal nutritional indicator (haemoglobin).

Objectives

This study reviewed the effects of maternal haemoglobin (Hb) on MMA of mother-infant pairs at birth.

Methods

One hundred and fifty three mother-infant pairs were enrolled in this study using the systematic random sampling method. Means of maternal Hb and MMA of mother-infant pairs were compared using the Student t test. Correlation coefficients of maternal Hb and MMA of mother-infant pairs were also determined. Multivariate analysis of variable (MANOVA) and covariates (MANCOVA) was used to investigate the effects of maternal Hb (fixed factor), gestational age, maternal age, birth weight (covariates) on combined MMA of mother-infant pairs (dependent factors). Benferroni adjusted Univariate linear regression was used to investigate the dependent variables separately.

Results

There were 78 (51%) males and 75 (49%) females. The (mean ± SD) MMA of mother-infant pairs at birth were 134.66 ± 93.31 (95% CI, 119.76 – 149.56) U/ml, and 187.49 ± 85.01 (95% CI, 173.91 – 201.07) U/ml, and their correlation was significant (p = 0.025). Ninety one (59.5 %) mothers had low Hb, 62 (40.5 %) had acceptable Hb levels. The overall mean maternal Hb was 11.01 ± 1.00 (95% CI, 10.85 – 11.17) g/dl . A positive significant correlation was observed between maternal Hb and MMA of the newborn-infant (p = 0.031). The MANOVA showed a statistically significant difference between maternal Hb on the combined dependent variables (p =0.033); however, results for the dependent variables using the Benferroni adjusted Univariate analysis was significant for only MMA of the infants, (p = 0.009).

Conclusion

There was a significant association between aacceptable levels of maternal Hb and high MMA of the newborn-infants. Therefore, these newborn infants start out with higher MMA that could give them better protection against measles during infancy.     

Maternal antibodies in human foetal sera at different stages of gestation

Complement-fixing antibodies to ten viral antigens and/or mercaptoethanol treated anti-streptolysin-O and anti-staphylolysin-α were determined in thirty human sera from foetuses at different stages of gestation, in fifty-seven full-term cord sera, and in the corresponding maternal sera. In the smallest foetuses (crown—heel length of 125–150 mm), no antibody was found. In those of length 155–215 mm, antibody was detectable if the corresponding maternal value was high. In foetuses of 230–380 mm, antibody was detected occasionally even when the maternal value was low. Sera of foetuses of 390 mm or more contained the same antibodies as the maternal sample, and foetal titres sometimes exceeded those of the mother. Titres in the full-term cord sera were significantly higher than the maternal titres for seven of the twelve antibodies studied.     

Evaluation of a Latex Agglutination Kit (Virogen Rotatest) for Detection of Bovine Rotavirus in Fecal Samples

The performance of the Virogen Rotatest latex agglutination test (LAT) was evaluated for detection of bovine rotavirus antigen. Sixty-three fecal samples from diarrheic calves were collected from November 1999 to May 2000 and screened by LAT, the Rotazyme II enzyme-linked immunosorbent assay (ELISA), and virus isolation (VI) followed by an anti-rotavirus fluorescent-antibody (FA) test to detect the presence of group A rotavirus antigen. Of the 63 samples screened by VI-FA, 33 (58%) tested positive for rotavirus antigen. When the results from the LAT were compared to those from VI-FA, the “gold standard” for detection of bovine rotavirus in fecal samples, the sensitivity and specificity were found to be 87.8 and 73.3%, respectively. Latex agglutination compared with ELISA (the reference method) showed 100% sensitivity and 96.3% specificity, and when ELISA was compared with VI, the sensitivity was 84.8% and the specificity was 73.3%. Latex agglutination is easy to perform in a short time and does not require expensive equipment or skilled personnel, and the reagents have long shelf lives. These factors make the LAT suitable and highly efficient for use in a clinical laboratory as a rapid screening test for bovine rotavirus.     

The study of the serological activity of papain-degraded antibodies by means of the complement fixation reaction

Summary As demonstrated, products of papain degradation of immune gamma-globulin do not fixate the complement in the presence of specific antigen; however, they competitionally inhibit the complement fixation reaction by unchanged serum and specific antigen. To ascertain the serological activity of papain-degradated antibodies, a method of inhibiting the complement fixation reaction has been developed, the sensitivity of which is 80–100 times that of the method of precipitation reaction inhibition used for this purpose formerly.(Presented by Active Member AMN SSSR N.N. Zhukov-Verezhnikov) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 54, No. 8, pp. 65–69, August, 1962     

Antigens of the Human Syncytiotrophoblast Microvillus Plasma Membrane*

ABSTRACT: Further data are presented on the isolation and biochemical analysis of syncytiotrophoblast microvillus plasma membrane preparations from normal full-term human placentas. No evidence has been obtained that IgG associated with these membranes is maternal antibody to trophoblast antigen. An oncotrophoblast plasma membrane antigen was previously identified by immunofluorescence, and an indirect radioisotopic antibody assay has now been used to confirm the detection of a cell surface antigen common to breast carcinoma cells and normal trophoblast. The relation of trophoblast plasma membrane antigens to possible maternal immunization in pregnancy is discussed.     

Intrauterine transmission of hepatitis B virus is closely related to placental leakage

Hepatitis B virus (HBV), transmitted by hepatitis B e antigen (HBeAg)-positive mothers by intrauterine infection, infecting newborns, is closely related to signs and symptoms associated with miscarriage. However, no correlation was observed between intrauterine infection of infants and the presence of antibodies of immunoglobulin M (IgM) class antibodies against hepatitis B core antigen (anti-HBc) in maternal blood, nor was HBeAg found in maternal or cord sera. These results indicate that contamination by the mother's blood, through placental leakage, plays an important role in HBV infection in utero. Without placental leakage, maternal blood could not pass through the placenta and enter fetal circulation, and so intrauterine infection would not occur, even if very high titers of hepatitis B surface antigen (HBsAg) and HBeAg were present in maternal blood.     

Habitual Abortion: Parental Sharing of HLA Antigens,Absence of Maternal Blocking Antibody,and Suppression of Maternal Lymphocytes

ABSTRACT: The immunologic responsiveness of eight women who habitually abort has been investigated. All shared an HLA-A or B antigen with their husbands. Sharing of an HLA-DR antigen was found in seven couples, one of which also had a second DR antigen in common. The probability for this high frequency of HLA-DR sharing is negligible (p = 0.0004), as calculated from the antigen frequencies among Europeans. Cells from the woman with two shared DR antigens displayed a minor response to her husband's cells but reacted strongly to control cells, whereas the other women's cells reacted normally to cells from both their husbands and controls in one-way mixed lymphocyte culture (MLC). Only minor cytotoxicity was displayed by women's cells in a direct cell-mediated lympholysis (CML) assay, but they mounted normal cytotoxic responses against both husbands' cells and control cells in an amplified CML assay. The sera from six of the habitually aborting women displayed no blocking activity in one-way MLC, and seven of them had no cytotoxic antibodies. Cells from all habitual aborters were suppressed in two-way MLC by cells from husbands and most controls. We hypothesize that increases in HLA compatibility between mother and fetus and in maternal susceptibility to suppressive influences are in some way linked to a deficiency in the development of anti-fetal antibody during pregnancy. As a consequence, the fetus may be deprived of the protection by maternal blocking antibody, which may allow maternal cytotoxic reactions to cause abortion.     

A slide antigen in the indirect fluorescent antibody test for Trichinella spiralis

A stable cuticular slide antigen was prepared for use in the indirect fluorescent antibody (IFA) test for trichinosis. Cuticles of Trichinella spiralis larvae, prepared by pepsin digestion, were embedded in Tissue-Tek OCT embedding medium, frozen, and sections made and mounted on slides. After storage at –70° for 2 days to allow the antigen sections to become firmly affixed to the slides, they may be used to perform the IFA test for trichinosis. This method is less time-consuming, due to the elimination of centrifugation steps, than the antigen presently in use for the trichinosis IFA test, and should be applicable to other IFA procedures.     

ORIGINAL ARTICLE: Enhanced Maternal Anti‐Fetal Immunity Contributes to the Severity of Hypertensive Disorder Complicating Pregnancy

Citation Liu L‐P, Huang W, Lu Y‐C, Liao A‐H. Enhanced maternal anti‐fetal immunity contributes to the severity of hypertensive disorder complicating pregnancy. Am J Reprod Immunol 2010 Problem The aim of this study was to evaluate how fetal monocyte activation and maternal anti‐fetal antigen‐specific antibody‐secreting cells (ASC) affect the severity of hypertensive disorder complicating pregnancy (HDCP). Method of study Forty‐six healthy third‐trimester pregnant women and 20 patients with gestational hypertension, 20 with mild pre‐ecalmpsia and another 20 with severe pre‐eclampsia were included in the study. Interleukin‐6 (IL‐6) release from cord blood monocytes was examined by intracellular cytokine staining and flow cytometric analysis. Moreover, the maternal anti‐fetal antigen‐specific ASC were detected by enzyme‐linked immunospot assay. Results A significantly increased percentage of IL‐6‐positive monocytes were detected in the cord blood of study groups compared with the controls (P < 0.01). The percentage of IL‐6‐positive monocytes was increased as the disease progressed (P < 0.05). There were more anti‐fetal antigen‐specific ASC in the study groups than those in the controls (P < 0.001). Furthermore, the anti‐fetal antigen‐specific ASC showed difference in gestational hypertensive and severe pre‐eclamptic groups (P < 0.05). Conclusion We conclude that the fetal monocyte activation and the increase in maternal anti‐fetal antigen‐specific ASC were related to the incidence and severity of HDCP. These results provide both indirect and direct evidence for the occurrence of exaggerated maternal humoral immunity against the fetal antigens in HDCP.     

Light-scattering studies of the formation of aggregates in mixtures of antigen and antibody

Formation of aggregates in mixtures of antigen and antibody was followed by measurement of the intensity of light scattered at 90° and of the ratio of the intensities of light scattered at 45° and 135° under varied environmental conditions—concentration, antigen/antibody ratio, temperature, concentration of neutral salts, hydrogen ion and organic solutes. We propose that the aggregation of antigen—antibody complexes is accelerated by change in the structure of antibody molecules that occurs on combination with antigen. The effect of solutes on the rate of aggregation may be due to reduction of the association constant of the combination of antigen and antibody or to inhibition of the change in structure of antibody on combination. Acceleration of the early stage of aggregation by increase of temperature is attributed to increased rate of change in the structure of antibody.     

Epitope analysis of the Goodpasture antigen using a resonant mirror biosensor

We have used a new technique for studying molecular interactions—a resonant mirror biosensor—to identify B cell epitopes within the Goodpasture antigen, which has recently been identified as the non-collagenous domain of the α3-chain of type IV collagen (α3(IV)NC1). Recombinant antigen (r-α3) was immobilized onto the sensing surface of a sample cuvette, and the binding of patients’ autoantibodies or a MoAb to the Goodpasture antigen was followed in real time. All patients’ sera bound r-α3 in this system, while control sera did not bind. A MoAb inhibited the binding of all patients’ autoantibodies to r-α3, from 27% to 90% (mean inhibition 60%), and patients’ sera cross-inhibited the binding of each other to the antigen. Binding was inhibited by pre-incubation of autoantibody with both native sheep α3(IV)NC1 and purified human α3(IV)NC1 monomers. Inhibition experiments using soluble overlapping peptides from human α3(IV)NC1 identified putative B cell epitopes. These results suggest that there is a major immunodominant epitope on the Goodpasture antigen, and that there is very limited heterogeneity in the autoantibody response in Goodpasture’s disease. The resonant mirror biosensor can be successfully used to monitor antibody–antigen binding using polyclonal sera, and to map epitopes on autoantigens.