High Total IgE Levels Research Articles

A Mechanism for Anti-Asialo GM 1 Antibody-Induced Anaphylactoid Response in Mice Infected with Trichinella pseudospiralis

Intravenous injection of anti-asialo GM 1 antibody into mice infected with Trichinella pseudospiralis resulted in rapid acute illness or death accompanied by a dramatic rise in hematocrit values in these animals. The described antibody-induced changes were reversible by intravenous infusion of Hanks' balanced salt solution (HBSS). These effects were not seen in uninfected mice or in Trichinella spiralis-infected mice injected with anti-asialo GM 1 antibody. Viability of T. spiralis or T. pseudospiralis infective L1 larvae, both isolated worms and those housed in muscle, was unaffected by exposure to anti-asialo GM 1 antibody and complement. Infectivity of larvae of T. pseudospiralis decreased significantly following exposure to anti-asialo GM 1 antibody. Release of protein by T. pseudospiralis infective L1 larvae during incubation in the presence of anti-asialo GM 1 antibody was significantly greater than that released by worms incubated in normal rabbit serum or HBSS. Protein released by infective L1 larvae of T. pseudospiralis was identified as Trichinella excretory/secretory antigens by immunoblot. Intravenous injection of T. pseudospiralis excretory/secretory products resulted in anaphylaxis in T. pseudospiralis-infected mice but not in uninfected or T. spiralis-infected mice. Excretory/secretory product-induced anaphylactoid response also was reversible by the intravenous injection of HBSS or by injection of an antihistamine. Significantly higher levels of total IgE were observed in sera from mice infected with T. pseudospiralis compared to uninfected or T. spiralis-infected mice. Binding of anti-asialo GM 1 antibody to the surface of T. pseudospiralis muscle larvae induced release of excretory/secretory antigen by the parasite.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunologic specificity of isocyanate-induced IgE antibodies in serum from 10 sensitized workers

A procedure for the preparation of RAST disks used to assay isocyanate-specific IgE antibodies was developed. The outcome of the RAST was found to be strongly dependent on how the isocyanate test antigen was synthesized. Specific IgE from selected workers with isocyanate asthma reacted optimally to conjugates with ⩽10 isocyanate molecules bound per molecule of human serum albumin. Further haptenization resulted in decreased specific binding and increased nonspecific binding because of high levels of total IgE. The hapten and carrier specificity of isocyanate-induced IgE antibodies were studied by direct RAST and RAST inhibition. The existence of new antigenic determinants related to both the isocyanate hapten and the carrier could be demonstrated. It was important to use a test antigen prepared from the same isocyanate as that to which the worker had been exposed, since the cross-reactivity between different isocyanate haptens was partial and varied from one patient to another, it was confirmed that isocyanate-specific IgE antibodies can be demonstrated only in a subgroup of workers with isocyanate-related bronchial asthma.

Serum immunoglobulins and immunoglobulin G subclasses in cystic fibrosis related to the clinical state of the patient

Levels of serum immunoglobulins and immunoglobulin G subclasses were measured in 32 cystic fibrosis (CF) patients, 30 asthmatics and 27 controls. When compared with the asthmatic patients and controls, the CF patients had raised levels of all IgG subclasses as well as total IgG, IgM and IgA, but there was not a statistically significant increase in IgE. The levels of immunoglobulins in the CF patients were examined in relation to the clinical features of the disease. Raised levels of IgG4 were related to levels of IgE, but these raised levels of IgG4 appeared to be part of a general increase in total IgG and not an isolated feature. There was a significant correlation between the total IgG level and its subclasses, IgG1, IgG2, IgG3, IgG4 and IgA. IgG1 was significantly correlated with IgG2 and IgG4; IgG2 with IgG4; and IgG4 with IgE. Total IgG was the immunoglobulin most closely correlated with poor lung function. Serum IgA was higher in patients with positive immediate skin prick reactions to pollens (p less than 0.005) and death within two years of the study was related to high levels of total IgG (p less than 0.01), IgG3 (p less than 0.001), IgA (p less than 0.001), and IgE (p less than 0.005).

Placebo-controlled double-blind food challenge in asthma

To determine the prevalence of food allergy as a cause of exacerbation of asthma, we studied 300 consecutive patients with asthma (7 months to 80 years of age) who attended a respiratory clinic. Each patient was screened for possible food allergy by means of a questionnaire and by skin prick tests with the six food allergens most common in our area. Patients with either a suggestive history and/or a positive prick test and/or RAST underwent double-blind food challenge with lyophilized food in capsules or food mixed in a broth to disguise its taste. Pulmonary function tests and symptoms were followed for 8 hours after each challenge. Of the 300 patients screened, only 25 had either a history or skin prick tests or RAST responses suggestive of food allergy. Twenty patients had interpretable food challenges. In these 20 patients, food challenge caused asthma in six and caused other symptoms (atopic dermatitis and gastrointestinal symptoms) in five. On rechallenge after pretreatment with disodium cromoglycate (300 mg 30 minutes before the food challenge), the asthmatic response was blocked in four of five subjects. The patients with asthma with food allergy were generally young, had a current or past history of atopic dermatitis, and high total serum IgE levels. Our findings confirm that food allergy can elicit asthma, but its incidence is low, even in the population attending a specialty clinic. Food elimination diets should not be prescribed for all patients reporting an adverse reaction to foods or having a positive skin prick test and/or RAST with food allergens. In patients with asthma caused by food allergy, disodium cromoglycate may be used to complement elimination diets.

111 SPECIFIC IMMUNOTHERAPY (SI) IN THE TREATMENT OF “MINOR” ALLERGIC RESPIRATORY DISEASE (MARD) (wheezy bronchitis and/or chronic cough)

We studied 224 children (ch) with high suspicion of MARD, aged 1 to 13 (x=4.6 yr) with more than 3 acute episodes during more than 6 months. We found an allergy family history in 71.9% and a high level of total IgE in 92%. We found positive results to house dust mites in 43.7% with prick test and in 51.8% with RAST. Both PT and/or RAST gave positive results in 68.7%. The follow-up study was conducted over 1 to 4 yr (x=2yr); 37 dropped out. We divided 150 proven atopic ch into 3 groups. Group A (69 ch) received a mast cell stabilizer drug (MCSD), group B (45 ch) SI with D.Pteron allergen plus MCSD, group C (36 ch) served as a control group. A marked improvement was seen in group B, whereas in group C only 1 of 6 ch showed any improvement. Group A showed intermediate results. During the study 50% of group C developed overt asthma against 30% in group A and only 4% (p <0.01) in group B. The results suggest that SI might have a preventive role in children with atopic MARD.

Proliferative response in solid culture of T cells from patients with extrinsic bronchial asthma.

T cells proliferative response in both liquid and solid culture conditions (the later prevents direct cell to cell contact) was investigated in nineteen Extrinsic Bronchial Asthma patients (EBA). Tetradecanoyl-phorbol-13-acetate (TPA), a T cell mitogen was used as mitogenic stimulus in both liquid and solid conditions. While the response to phytohemaglutinin (used in liquid culture as reference) was intact, the EBA group showed a significant reduction in the proliferative response to TPA in both culture conditions. Furthermore, when adherent cells were removed prior to TPA stimulation, while the control group showed a significant decrease in proliferation, the already depressed low proliferation of the EBA group remained unchanged. These results suggest the prevalence of suppressor signals in EBA and may indicate heterogeneity of the suppressor cells pool since high levels of total serum IgE were also present in the same patients.

First Case of Acquired Functional CI INH Deficiency: Association with Angioedema during Churg and Strauss Vasculitis

This report deals with the first case of acquired functional C1(-) INH deficiency with normal antigenic C1(-) INH level which was detected in a young girl with angioedema and Churg and Strauss vasculitis. This complement abnormality was associated with slightly depressed levels of CH50, C4 and C2, but a normal level of C3, and high levels of total IgE and IgM rheumatoid factors. Finally, most of these abnormalities disappeared after corticosteroid therapy and clinical improvement.

Allergen-specific immunoglobulin E antibodies in tears and serum of vernal conjunctivitis patients.

Tears and sera of 53 patients of vernal conjunctivitis were examined for antibodies of the IgE type to a panel of 18 allergens. In 18 of the patients (34.0%) allergen-specific IgE was demonstrated in both tears and serum, in 3 (5.7%) in tears only, and in 4 (7.5%) in serum only. The antigen-specific reactions with tear fluid were found in patients with the highest total IgE levels, not only in tears but also in serum. This is evidence for a specific, local allergic reaction in these patients. Most positive reactions were to perennial allergens, particularly house dust mites, cat epithelium and Bermuda grass. This fact is in harmony with the lack of season-linked symptoms in most patients in this geographical area.

Allergic reactivity and helminthic infection in Amerindians of the Amazon Basin.

Various aspects of the allergic reactivity of Amerindians in the Venezuelan sector of the Amazon basin were examined. The frequency of positivity in immediate hypersensitivity skin tests with extracts of common local environmental allergens was found to be extremely low (6.7%). As sera from significantly higher proportions of the study group contained specific IgE antibody against the test allergens, and their histamine-induced skin responses were normal, these results support previous suggestions of an inhibited expression of allergic reactivity in such populations. Indeed, the intense helminthic infections detected, and the extremely high total serum IgE levels measured (geometric mean 13,088 IU/ml) indicate the possible occurrence of mast cell saturation by parasite-induced IgE. However, despite a similar lack of agreement between the in vivo and in vitro tests for allergic reactivity against Ascaris lumbricoides in these subjects (43.5 and 97.9% positive, respectively), their extremely high responsiveness to the helminth allergens presents a marked contrast to that against the other environmental materials. Factors other than helminthiasis (e.g. racial, cultural, nutritional) might, therefore, also modulate the expression of allergic reactivity in such populations.

Association between the MB system and asthma in the Japanese

Twenty-three unrelated Japanese patients with asthma who showed a high total serum IgE level, a strong skin test response to Dermatophagoides farinae, and a high score on a radioallergosorbent test (RAST) using Dermatophagoides farinae were typed for HLA-A locus. -B locus, and -D region antigens. No significant difference in the frequencies of HLA-A. B. and -DR antigens were observed between the asthma patients and the healthy controls. A significant difference in the frequency of MB3′, however, was found between the asthma patients and the healthy controls (p = 0.04, relative risk = 18.5).

Toluene-diisocyanate induced asthma: evaluation of antibodies in the serum of affected workers against a tolyl mono-isocyanate protein conjugate.

Radioallergosorbent testing was used to look for the presence of specific IgE antibody against a para-tolyl-mono-isocyanate human serum albumin conjugate in sera from five groups of subjects. The first three groups consisted of individuals exposed to toluene diisocyanate (TDI) who had been shown by bronchial provocation testing with levels of TDI below the threshold limit value of 0.02 parts/10(6), to have immediate asthmatic reactions, late asthmatic reactions or no respiratory changes at all. The two control groups consisted of atopic and non-atopic individuals who had no respiratory symptoms and no known exposure to TDI. Although RAST showed high ct/min in some of the sera from patients with proven TDI-induced respiratory disease, these levels were not significantly different from controls and appeared to reflect the presence in these sera of high levels of total IgE (greater than 100 mu ml--1). There is no evidence from this study for the presence of specific IgE antibody against a para-tolyl mono isocyanate human serum albumin conjugate in patients with TDI-induced respiratory disease. This finding may reflect absence of antibodies, or that the techniques for their detection are not always effective even when performed by experienced persons, and there is a potential source of error in the interpretation of results when sera contain large amounts of IgE.

Influence of dialysable transfer factor on IgE concentrations in patients with atopic dermatitis.

Dialysable transfer factor (TF) was given in 10 paediatric patients with severe atopic dermatitis (AD). Ten patients with AD, matched for age and severity of disease, served as controls. Prior to the therapy with TF and at weekly intervals thereafter, T- and B-cells in the blood, PHA-stimulation, total IgE and specific IgG antibodies to inhalant and food antigens were determined. Therapy with TF was followed by IgE depression in 8/10 patients and was most pronounced in three patients with initially high levels. Some decrease of IgE levels was seen in four controls also, none of them, however, fell to normal levels as was seen in two of the treated patients. Specific IgE levels decreased slightly, but always remained within the pathological range. T-cell counts in the blood increased in 2/10 cases as well as PHA-stimulation, B-cells counts remained within normal limits. Clinical improvement was seen in one patient, five improved slightly and four remained unchanged. Our results indicate, that transfer factor can lower total IgE levels in cases with atopic dermatitis. The effect is most marked in patients with high total IgE levels. Skin involvement, however, does not closely follow in vitro findings.

Species specificity of the immediate hypersensitivity to schistosomal proteolytic enzyme

An acidic proteolytic enzyme which digests host haemoglobin can be isolated and purified from schistosomes. This small glycoprotein is an allergen which sensitizes the host, as shown by immediate hypersensitivity reactions. These are specific for either Schistosoma haematobium or S. mansoni and can be demonstrated by mast cell degranulation in mice or by intradermal skin tests in monkeys. Although high levels of total IgE may be found in acute and chronic schistosomiasis, there was no evident relationship between the worm burden in monkeys and immediate hypersensitivity reactions to either purified enzyme or crude schistosomal extracts. It is suggested that an in vivo correlation between worm burden and manifestations of the allergic response may be perturbed by high titres of non-specific IgE or other homocytotropic antibodies, thus accounting for false negative skin test reactions. Alternatively, a return to low or subnormal IgE levels may allow the restoration of the allergic response, giving rise to false positive reactions. Purified schistosomal antigens offer certain advantages over crude skin test preparations in terms of uniformity of antigen content, dosage and specificity. In addition, the enzyme may represent a species-specific tool for new immunochemical analyses of schistosomiasis.

Relation between Total Serum IgE Levels and IgE Antibody Production in Rats

Five different rat strains were immunized with 100 microgram ovalbumin and 1 mg Al (OH)3. A good correlation was found between the total serum IgE level of a rat strain before immunization and the IgE antibody production. Good IgE antibody-producing strains had high total serum IgE levels and vice versa. A discordance between the evolution of the total serum IgE level after immunization and the changes in IgE antibody level was found in all strains.

Tolyl-specific IgE antibodies in workers with hypersensitivity to toluene diisocyanate

Incorporation of a p-tolyl (mono) isocyanate-human serum albumin (TMI-HSA) antigen conjugate into a solid phase radioimmunoassay permitted detection of tolyl-specific IgE antibodies in 3 of 4 workers with clinical hypersensitivity to toluene diisocyanate (TDI). By comparison 19 TDI-exposed, non-sensitized workers had antibody titers similar to those found in normal adults. High titers of tolyl-specific IgE antibodies were not correlated with high levels of total serum IgE. Use of the monofunctional isocyanate in place of TDI in antigen preparation prevented cross-linking of antigen protein, an effect usually associated with TDI, and also assured that tolyl groups were sterically exposed. TMI-HSA antigens may prove beneficial in serological or cutaneous evaluation of TDI-sensitized workers.

A method for the simultaneous determination of serum and cell-bound IgE.

A method for determining the amount of total IgE bound to leucocytes has been devised by measuring that released on incubating various cell number dilutions in acetate buffer pH 4-0. A linear relationship between IgE released and cell number was obtained over a limited concentration range. The method seemed to work satisfactorily with 50 ml of whole blood for those subjects with very high serum levels of total IgE. However, with subjects having a slightly elevated or normal serum IgE level it may be necessary to use twice the amount of blood.

Heat studies with human IgE: a simple method for rapidly distinguishing sera with high total IgE levels.

SummaryHuman sera, covering a wide range of total IgE concentrations, were subjected to mild heat treatment for varying periods of time and then examined for their abilities to bind to an Fc‐specific, radioactively labelled rabbit anti‐human IgE serum. As a result of the heat treatment, aggregation of the serum IgE occurred and the aggregated material reacted significantly with the labelled antiserum. Experiments with a standard human IgE serum and over 100 different human serum samples from normal and allergic patients showed that this simple heat method can distinguish high, medium and low levels of IgE in serum. Provided that sufficient examinations are undertaken, the method offers a simple means of rapidly examining large numbers of serum samples and distinguishing those sera with elevated levels of IgE.Differences observed between individual serum samples may indicate physico‐chemical differences in the IgE molecules present in the sera. Such differences may be a further reflection of the heterogeneity of human IgE. The stability of human skin‐sensitizing antibodies is briefly reviewed.