Are deficiencies of prostaglandin-E-mediated immunoregulation involved in increased IgE synthesis of atopic mononuclear cells in vitro?

We demonstrate that spontaneous in vitro immunoglobulin E synthesis of atopic peripheral blood mononuclear cells could be suppressed by the addition of 10(-6) M to 10(-5) M prostaglandin E1 (PGE1) or PGE2. Impaired suppressor T lymphocyte maturation and function in atopic individuals are explained by an insufficient transmission of prostaglandin E (PGE) signals during thymic lymphocyte differentiation as well as an impaired ability of the atopic immune system to activate suppressor T cells by PGE-mediated feed back mechanisms. Decreased levels of 6-desaturated PGE-precursor fatty acids in plasma, T lymphocytes, monocytes, adipose tissue and breast milk have been observed in atopic individuals. These insights might offer a novel approach to the prevention of atopic disease by substitution of the atopic pregnant and nursing woman and her newborn infant with long-chain omega-6-fatty acids.     

Time-dependent study of the antibody response to sperm-whale myoglobin: recognition of the antigenic sites is unaltered over an extended period of immunization

We have recently shown that the antigenic structure of sperm-whale myoglobin is not dependent on the host species in which the antisera are raised. The purpose of the present work was to determine whether or not the molecular immune recognition of a protein by antibody is subject to a time-dependency. We have investigated the recognition of the antigenic sites by serial antisera obtained in two rabbits at different times after the initial immunization, from the earliest bleeding with detectable antibodies (9 days) up to a year. The specificity of these antisera was determined by their cross-reactions with 13 myoglobins from different species. The reactivity was measured by quantitative immunoadsorbent titration studies from the amount of radioiodinated antibodies that could be bound maximally (i.e. plateau binding values) by immunoadsorbents of each myoglobin. From these studies and our recent structural analysis, which enabled us to identify for each of these myoglobins the regions retaining reactivity with antibodies to sperm-whale myoglobin, we have concluded that following maturation of the immune response the antigenic recognition of a protein (i.e. the regions that are recognized as antigenic) is not dependent upon the time antisera are obtained after the first immunization. In the early periods of the response, fluctuations are observed in the relative immunodominance of the sites. This further confirms our earlier conclusions that the antigenic sites on a protein are structurally inherent in the protein.     

Detection of radiolabelled bone marrow cells bearing surface ace immunoglobulins by combined autoradiography and immunoperoxidase

A method is described for the simultaneous detection of radiolabelled bone marrow cells bearing surface immunoglobulins by combined autoradiography and immunoperoxidase. Bone marrow cells from normal CBA mice prelabelled in vivo with ¹²⁵IUDR or exposed in vitro to [³H]thymidine were incubated with rabbit anti-mouse immunoglobulins under capping conditions, washed, cytocentrifuged and treated with methanol and hydrogen peroxide to destroy endogenous peroxidase. Cells were then covered with peroxidase-conjugated goat anti-rabbit immunoglobulins, washed, treated with diaminobenzidine a and hydrogen peroxide and finally covered with autoradiographic stripping film and exposed for different times. Peroxidase-positive cells were typically capped and those radiolabelled had autoradiographic silver grains overlying the nucleus.     

Acquired α2 macroglobulin on the surface of human lymphoblastoid cells

The molecular nature of the membrane antigen that is acquired from FCS-containing media by human lymphoblastoid cells has been investigated. The presence of bovine α₂, macroglobulin on the surface of Namalva cells was demonstrated by radioimmunoassay using specific antisera. Alternatively, cell-bound bovine α₂,M could be detected by the more sensitive heterophile rosette assay described previously. Namalva cells grown in NHS-containing media acquired bovine α₂ M upon subsequent incubation with the purified protein in a dose- and time-dependent way. Acquisition of α₂ M was demonstrated using both viable and formaldehyde-fixed cells. Purified fetuin, which carries a heterophile epitope shared with bovine α₂ M as well as with other glycoproteins, failed to bind with the membrane of Namalva cells. The possible role of acquired α₂ macroglobulin on cells has been discussed.     

Utility of the ratio of food-specific IgE/total IgE in predicting symptomatic food allergy in children

BACKGROUND: Double-blind, placebo-controlled food challenges are time-consuming, expensive and not without risk to patients. Therefore, an in vitro test that could accurately diagnose food allergy would be of great value. OBJECTIVE: To evaluate the utility of the ratio of specific immunoglobulin E (IgE)/total IgE compared with specific IgE (sIgE) alone in predicting symptomatic food allergy. METHODS: We retrospectively analysed 992 controlled oral food challenges performed in 501 children (median age 13 months). The ratio of sIgE/total IgE was calculated and tested for correlation with the outcome of food challenges. Receiver operator characteristics (ROC)-curves were performed; predicted probabilities and predictive decision points were calculated. RESULTS: A significant correlation was found between the ratio and the outcome of food challenges for cow's milk (CM), hen's egg (HE), and wheat, but not for soy. The ROC and predicted probability curves as well as sensitivity and specificity of the decision points of the ratio were similar to those of sIgE levels for CM, HE and wheat. CONCLUSION: In view of the greater effort needed to determine the ratio, without benefit compared with the sIgE alone, the calculation of the ratio of sIgE/total IgE for diagnosing symptomatic food allergy offers no advantage for CM, HE, wheat or soy. For the majority of cases controlled oral food challenges still remain the method of choice.     

Synergistic convergence of microbiota-specific systemic IgG and secretory IgA

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Desensitization protocols improving access and outcome in transplantation

Sensitization to antigens of the HLA and ABO system has been the biggest barrier to access in renal transplantation and, increasingly, in transplantation of other organs. Additionally, antibody to donor antigens has been shown to result in injury to the graft ranging from catastrophic, irreversible hyperacute rejection to the slower, more insidious, chronic form of rejection. The problem of access has been recognized globally and has been the incentive for measures to overcome the disadvantage experienced by the sensitized patient. However, early attempts to reduce sensitization achieved only transient success. Newer immunosuppressive agents that affect B-cell function or viability have permitted the development of treatment protocols to eliminate and, potentially, downregulate donor-specific antibodies. The use of these protocols has achieved successful transplants that were HLA and/or ABO incompatible prior to treatment and, as such, has provided some patients with their only opportunity for transplantation.     

Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage

Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage An alloimmune abnormality is believed to be the cause of recurrent miscarriage in couples in whom no other cause can be identified. Because of its immunosuppressive properties, intravenous immunoglobulin (IVIG) is used as a treatment for this disorder. The purpose of this study was to determine whether IVIG improves the chance of successful pregnancy in women with recurrent miscarriage by using individual patient data from efficacy trials. Detailed information on each patient enrolled in these trials was obtained to evaluate the efficacy of IVIG and investigate the effect of clinical variability on pregnancy outcome. Data from 125 patients in the IVIG group and 115 patients in the placebo group were available for analysis. Although the number of previous miscarriages and female age were both negative prognostic factors for successful outcome, there was no significant improvement in successful pregnancy or live birth rate with IVIG. Subgroup analyses indicated that timing of IVIG administration may be important. The results of the present study highlight the importance of stratification for known confounders, so that the role of IVIG can be evaluated in more detail. The collective evidence thus far indicates that IVIG does not have a therapeutic effect that is clinically meaningful.     

Serum levels of total IgE in non-allergic children

The purpose of this study was to establish the range of total serum IgE in a healthy population lacking personal and family history of allergy, as well as the influence of genetic factors (family history of allergy), environmental factors (degree of air pollution), age, and sex on the serum IgE levels. Using a commercial enzyme immunoassay (Phadezym IgE Prist) the mean serum level of IgE was determined in 363 non-atopic children from 0 to 12 years of age. The geometric mean of serum IgE increased according to age, indicating a positive correlation between both. Higher mean values of serum IgE were found for children with a family history of allergy, than for children without (27.82 and 14.49 U/ml respectively). The percentage of variation due to age was about 94.5% in children with no family history of allergy. The mean value of serum IgE increased with the degree of air pollution in the living area (15.49 U/ml in non-polluted areas, 20.78 U/ml in very polluted areas). However, the influence of air pollution was smaller than the influence of family history on the mean values of serum IgE. The mean value of serum IgE was not modified by sex.