Serum immunoglobulins in patients with carcinoma of the oral cavity,uterine cervix and breast

Summary Serum immunoglobulin levels (IgG, IgA, IgM, IgD and IgE) were estimated in 196 patients with carcinoma of the oral cavity, 172 patients with cervical cancer and 166 patients with breast cancer. The values were compared with those of 50 patients with benign lesions of the breast and cervix and 100 healthy adult controls. Only the serum IgE levels were found to be elevated in the benign group. Serum IgA, IgD and IgE levels were found to be elevated in all the three types of cancers and the levels were found to increase with clinical stage. In carcinoma of uterine cervix IgG levels were also found to be elevated. Immunoglobulins A and D returned to normal after clinical cure whereas IgE remained slightly elevated. IgD and IgE remained high in patients who had residual cancer.     

The determination of allergen-specific IgE and IgG antibodies in patients sensitized to the house dust mite Dermatophagoides pteronyssinus

45 patients, hypersensitive to house-dust mites, were examined by the method of skin tests to D. pteronyssinus allergen. Besides, in their blood sera the levels of allergen-specific IgE antibodies were determined in the radioallergosorbent test and allergen-specific IgG antibodies, in the enzyme immunoassay. These tests revealed that in 91% of the patients the results of skin tests were positive, in 68% an elevated level of specific IgE antibodies and in 93% of the patients an elevated level of specific IgG antibodies were detected. All patients showed the positive result in one of the above-mentioned tests. The largest group of the patients (55%) included persons showing the positive result of the skin test and having elevated levels of allergen-specific IgG and IgE antibodies. Thus, in cases of hypersensitivity to house-dust mites the levels of allergen-specific IgG and IgE antibodies in the patients' blood sera should be determined.     

Eosinophil cationic protein, specific IgE and IgG4 in human toxocariasis

Among 67 French patients presenting a toxocaral infection, various demographic, environmental, clinical and laboratory parameters (blood eosinophil count, eosinophil cationic protein (ECP), serum total IgE, specific IgE against common inhalant allergens, specific IgE and IgG4 against Toxocara excretory-secretory antigens) were investigated. Correlation studies and logistic regression analyses were conducted, testing elevated levels of ECP, specific anti-Toxocara IgE or IgG4 as outcome variables An elevated ECP level was significantly associated with both cough and rhinitis, a high level of specific anti-Toxocara IgE with itchy rashes and possible atopic status, and an increase of specific anti-Toxocara IgG4 with rural residence.     

Autoantibodies to thyroid gland antigens in chronic relapsing urticaria

The content of total IgE, antibodies to thyroglobulin (TG-Ab), antibodies to thyreoid peroxidase (TPO-Ab) in the blood serum and skin reaction to autologous serum were detected in patients with chronic relapsing urticaria (CRU). The skin test to autologous serum yielded positive results in 42% of the patients. The elevated levels of TG-Ab and TPO-Ab were detected in 30.7% and 35.4% of the patients, the elevated level of total IgE was detected in 60% of the patients. At the same time the detection rates of antithyreoid antibodies and the elevated level of IgE were not linked with skin reaction to autologous serum. Apparently, in addition to autoantibodies to IgE or its receptor (the positive skin test to autologous serum), thyroid gland antibodies may take part in the mechanism of the CRU formation.     

Frequency analysis of IgE-secreting B lymphocytes in persons with normal or elevated serum IgE levels

The immunoregulatory mechanisms that determine the high serum IgE antibody levels in disorders such as helminth parasite infections and the hyper-IgE recurrent infection syndrome (HIE) remain poorly understood. To assess whether elevated serum IgE levels result from an increased number of B lymphocytes committed to IgE production, the proportion of IgE-producing B lymphocytes was determined by a filter immunoplaque assay using PBMC from persons with a broad range of serum IgE levels that included normal persons (n = 9) and patients with loiasis (n = 12), tropical pulmonary eosinophilia (TPE) (n = 6), lymphatic filariasis (n = 28), and HIE (n = 8). PBMC from these persons were assessed for production of in vitro IgE. The geometric mean number of IgE-secreting cells in 10(5) B lymphocytes in PBMC was 0.42 (range 0-2.2) in normal persons, 5.6 (range 0.1-35.5) among patients with loiasis, 9.4 (range 0-53.2) among patients with lymphatic filariasis, 52 (range 31.5-115) among patients with TPE, and 218 (range 56-1404) among patients with HIE. When all study subjects were grouped, there were significant correlations with serum IgE levels (r2 = 0.78; p less than 0.0001) and net spontaneous in vitro IgE production (r2 = 0.8; p less than 0.0001). Estimates of the amount of IgE production per B lymphocyte were similar among normal persons, patients with filarial infections, and patients with TPE (geometric means of 134, 96, and 141 pg/ml/cell, respectively); in contrast, for HIE patients, IgE production by individual B cells was significantly lower (geometric mean 28 pg/ml/cell; p less than 0.001). These observations demonstrate that clonal expansion of IgE-producing B lymphocytes is a major mechanism underlying the elevated serum IgE levels seen in persons with hyper-IgE states.     

Analysis of lymphocyte response to chironomid midge antigens in asthmatic and non-asthmatic individuals

Chironomid antigens are currently one of the important allergens for bronchial asthma in Japan. We evaluated in vitro responses of peripheral blood lymphocytes (PBLs) to chironomid antigens and compared these responses with serum IgE levels. PBLs from adult asthmatic patients showed stronger proliferation in response to the extract of adult midges of Chironomus yoshimatsui compared with healthy adults. On the other hand, elevated PBL responses of child asthmatic patients to chironomid antigens were not observed. There was no significant correlation between PBL proliferation and the serum IgE level. Our results might suggest that elevated PBL proliferation in response to chironomid allergens has somehow important pathogenic roles in adult cases although this does not correlate directly with specific IgE production.     

A soluble form of the high affinity IgE receptor, Fc-epsilon-RI, circulates in human serum

Soluble IgE receptors are potential in vivo modulators of IgE-mediated immune responses and are thus important for our basic understanding of allergic responses. We here characterize a novel soluble version of the IgE-binding alpha-chain of Fc-epsilon-RI (sFcεRI), the high affinity receptor for IgE. sFcεRI immunoprecipitates as a protein of ～40 kDa and contains an intact IgE-binding site. In human serum, sFcεRI is found as a soluble free IgE receptor as well as a complex with IgE. Using a newly established ELISA, we show that serum sFcεRI levels correlate with serum IgE in patients with elevated IgE. We also show that serum of individuals with normal IgE levels can be found to contain high levels of sFcεRI. After IgE-antigen-mediated crosslinking of surface FcεRI, we detect sFcεRI in the exosome-depleted, soluble fraction of cell culture supernatants. We further show that sFcεRI can block binding of IgE to FcεRI expressed at the cell surface. In summary, we here describe the alpha-chain of FcεRI as a circulating soluble IgE receptor isoform in human serum.     

Correlation between airborne pollen incidence,skin prick tests and serum immunoglobulins in allergic people in cracowm,poland

Fifty patients suffering from pollen allergy were observed during the period 1988–1989. At the same airborne pollen content was examined using volumetric and gravimetric sampling methods.

The mean daily symptom scores and percentages of patients with symptoms of allergy during the pollen season correlated positively with the airborne pollen content of wild Gramincae and Cerealia (Secale cereale).

Skin prick test results and elevated levels of specific serum IgE confirmed the presence of allergy to these taxa in the patients observed. Allergy to tree pollen and herb pollen was confirmed in only 3 cases.

Elevated levels of specific serum IgE for Dactylis glomerata, Pltleum pratense, and Secale cereale appeared in 70–80% of patients. Specific serum IgE levels correlated more with skin prick reactions (especially with late phase reactions) than with total serum IgE levels. Airborne pollen concentrations evaluated by volumetric sampling (Burckard trap) ad by a gravimetric method differ in so many details, that their results are not comparable. However, both methods provide largely similar information about the presence of airborne pollen presence.     

Role for IgE in airway secretions: IgE immune complexes are more potent inducers than antigen alone of airway inflammation in a murine model

IgE is present in airway secretions from human patients with allergic rhinitis and bronchial asthma. However, the contribution of IgE present locally to the overall airway inflammation is not well understood. We hypothesize that Ag-specific IgE can capture airborne Ags and form immune complexes. These immune complexes may function as potent inducers of immune responses in the lung, contributing to the perpetuation of airway inflammation. BALB/c mice were first sensitized with OVA in alum systemically and then challenged with nebulized OVA. Bronchoalveolar lavage (BAL) fluid from these mice contained significant amounts of IgE, of which >50% was Ag specific. The IgE levels in airway secretions remained elevated for more than 15 days after the termination of Ag exposure. Significant amounts of IgE-OVA immune complexes were detected in BAL fluid from the OVA-challenged mice. For comparison of IgE immune complexes vs Ag alone, we treated OVA-immunized mice with intranasal administration of trinitrophenyl-OVA or trinitrophenyl-OVA-anti-DNP IgE. Those treated with the immune complexes showed significantly higher levels of IL-4 and more pronounced eosinophilia in BAL fluid than did those receiving the Ag alone. The IgE immune complexes did not augment the inflammatory response in high affinity IgE receptor (FcepsilonRI)-deficient mice. We conclude that IgE present in the airways can capture the Ag and that the immune complexes thus formed may augment allergic airway response in an FcepsilonRI-dependent manner. Thus, IgE present in airway secretions may facilitate Ag-mediated allergic airway inflammation.     

A genetic study of immunoglobulin E and atopic disease based on families ascertained through asthmatic children

In order to investigate the modes of inheritance of serum immunoglobulin E (IgE) levels and atopic disease, serum IgE levels and data on allergic disease were obtained from 42 families ascertained through asthmatic children visiting an allergy clinic. Although the mean IgE levels were elevated (mean 637 U/ml), the prevalence of atopic disease in this population was surprisingly low. When the data were analyzed using complex segregation analysis, no major locus could be detected. Moreover, the polygenic heritability was unexpectedly small even though the correlation between serum IgE levels and the liability to atopic disease was around 0.4. Given this unusual set of findings, it is postulated that parasitic infections in this population have (in accordance with well-established results of parasitic disease) caused both elevated levels of serum IgE and a decreased prevalence of allergic disease with the possible masking of the various genetic components of serum IgE levels and atopic disease.     

Analysis of IgE turnover in non-sensitized and sensitized rats

BACKGROUND: Although the levels of immunoglobulin E (IgE) in the circulating blood are often elevated in patients with allergic diseases, such levels cannot always be considered as pathognomonic signs of allergy. The induction of allergic reactions in the tissue was inferred to be related to the amount of IgE passing through the vascular wall. AIMS: We attempted to clarify which compartment, the intravascular or extravascular, plays an important role in the regulation of the turnover of rat IgE. METHODS: The level of DNP-specific rat IgE in the serum was estimated by IgE-capture enzyme-linked immunosorbent assay, and the turnover of IgE was analyzed from its pharmacokinetic parameters. RESULTS: The transfer rate constants from the central to tissue compartment (Kct) were larger than those from the tissue to central compartment (Ktc) irrespective of the sensitized state. The value of the distribution volume of the tissue compartment (Vt) was larger than that of the distribution volume of the central compartment (Vc) irrespective of the sensitized state. CONCLUSIONS: These Findings suggest that the short half-life of rat IgE in the circulation could be attributable to the distribution of IgE from the intravascular to the extravascular compartment.     

HLA-DR2, [HLA-B7, SC31, DR2], and [HLA-B8, SC01, DR3] haplotypes distinguish subjects with asthma from those with rhinitis only in ragweed pollen allergy.

MHC haplotypes were determined for 52 patients with ragweed pollen allergy, with and without asthma, and 27 non-atopic controls. Total IgE levels were unimodally distributed in all study groups and were higher in atopic patients in general compared with non-atopics. There was no difference in total IgE levels in patients with rhinitis only compared with those with rhinitis and asthma. IgE anti-Amb a V was detected (after subtraction of values representing the means + 2 SD of the non-atopics) in 9 of 20 asthmatics but only 3 of 32 patients with only rhinitis and was thus associated with asthma. Mean anti-Amb a V was much higher in the antibody-positive asthmatics (1710 U/ml) than in the positive patients with rhinitis only (469 U/ml). The extended MHC haplotype [HLA-B7, SC31, DR2] and its possible DR-containing fragment (SC31, DR2), were found almost exclusively among the patients with IgE anti-Amb a V and were significantly elevated in patients with asthma. DR2 in general, but not DR2 without SC31, was significantly increased in frequency in patients with anti-Amb a V. In contrast, the extended haplotype [HLA-B8, SC01, DR3] and DR3 in general were increased among patients with rhinitis only and patients without IgE anti-Amb a V compared with general controls. Thus, [HLA-B8, SC01, DR3] and DR3 appear to be "protective" for the production of this antibody and the occurrence of asthma. The findings are consistent with an MHC-linked gene or genes on [HLA-B7, SC31, DR2] (but not necessarily DR2, Dw2, or DQw6 in general) controlling the IgE immune response to Amb a V and associated with asthma in ragweed pollen-sensitive subjects. In patients with rhinitis alone and generally undetectable levels of IgE anti-Amb a V, the increase in [HLA-B8, SC01, DR3] and DR3 may mark a response to an as yet unidentified Ag associated with ragweed allergy and rhinitis only.     

Human Eosinophils Express the High Affinity IgE Receptor,FcεRI,in Bullous Pemphigoid

Bullous pemphigoid (BP) is an autoimmune blistering disease mediated by autoantibodies targeting BP180 (type XVII collagen). Patient sera and tissues typically have IgG and IgE autoantibodies and elevated eosinophil numbers. Although the pathogenicity of the IgE autoantibodies is established in BP, their contribution to the disease process is not well understood. Our aims were two-fold: 1) To establish the clinical relationships between total and BP180-specific IgE, eosinophilia and other markers of disease activity; and 2) To determine if eosinophils from BP patients express the high affinity IgE receptor, FcεRI, as a potential mechanism of action for IgE in BP. Our analysis of 48 untreated BP patients revealed a correlation between BP180 IgG and both BP180 IgE and peripheral eosinophil count. Additionally, we established a correlation between total IgE concentration and both BP180 IgE levels and eosinophil count. When only sera from patients (n = 16) with total IgE≥400 IU/ml were analyzed, BP180 IgG levels correlated with disease severity, BP230 IgG, total circulating IgE and BP180 IgE. Finally, peripheral eosinophil count correlated more strongly with levels of BP180 IgE then with BP180 IgG. Next, eosinophil FcεRI expression was investigated in the blood and skin using several methods. Peripheral eosinophils from BP patients expressed mRNA for all three chains (α, β and γ) of the FcεRI. Surface expression of the FcεRIα was confirmed on both peripheral and tissue eosinophils from most BP patients by immunostaining. Furthermore, using a proximity ligation assay, interaction of the α- and β-chains of the FcεRI was observed in some biopsy specimens, suggesting tissue expression of the trimeric receptor form in some patients. These studies provide clinical support for the relevance of IgE in BP disease and provide one mechanism of action of these antibodies, via binding to the FcεRI on eosinophils.     

Regulation and dysregulation of immunoglobulin E: a molecular and clinical perspective

Background

Altered levels of Immunoglobulin E (IgE) represent a dysregulation of IgE synthesis and may be seen in a variety of immunological disorders. The object of this review is to summarize the historical and molecular aspects of IgE synthesis and the disorders associated with dysregulation of IgE production.

Methods

Articles published in Medline/PubMed were searched with the keyword Immunoglobulin E and specific terms such as class switch recombination, deficiency and/or specific disease conditions (atopy, neoplasia, renal disease, myeloma, etc.). The selected papers included reviews, case reports, retrospective reviews and molecular mechanisms. Studies involving both sexes and all ages were included in the analysis.

Results

Both very low and elevated levels of IgE may be seen in clinical practice. Major advancements have been made in our understanding of the molecular basis of IgE class switching including roles for T cells, cytokines and T regulatory (or Treg) cells in this process. Dysregulation of this process may result in either elevated IgE levels or IgE deficiency.

Conclusion

Evaluation of a patient with elevated IgE must involve a detailed differential diagnosis and consideration of various immunological and non-immunological disorders. The use of appropriate tests will allow the correct diagnosis to be made. This can often assist in the development of tailored treatments.     

Relationships between Levels of Serum IgE,Cell-Bound IgE,and IgE-Receptors on Peripheral Blood Cells in a Pediatric Population

Background

Elevated serum immunoglobulin (Ig) E is a diagnostic marker of immediate-type allergic reactions. We hypothesize that serum IgE does not necessarily reflect total body IgE because in vivo IgE can be bound to cell surface receptors such as FcεRI and FcεRII (CD23). The aim of this study was to analyze the relationships between levels of serum IgE, cell-bound IgE, and IgE-receptors on peripheral blood cells in a pediatric population.

Methodology

Whole blood samples from 48 children (26 boys, 22 girls, mean age 10,3±5,4 years) were analyzed by flow cytometry for FcεRI, CD23, and cell-bound IgE on dendritic cells (CD11c+MHC class II+), monocytes (CD14+), basophils (CD123+MHC class II-) and neutrophils (myeloperoxidase+). Total serum IgE was measured by ELISA and converted into z-units to account for age-dependent normal ranges. Correlations were calculated using Spearman rank correlation test.

Principal Findings

Dendritic cells, monocytes, basophils, and neutrophils expressed the high affinity IgE-receptor FcεRI. Dendritic cells and monocytes also expressed the low affinity receptor CD23. The majority of IgE-receptor positive cells carried IgE on their surface. Expression of both IgE receptors was tightly correlated with cell-bound IgE. In general, cell-bound IgE on FcεRI+ cells correlated well with serum IgE. However, some patients carried high amounts of cell-bound IgE despite low total serum IgE levels.

Conclusion/Significance

In pediatric patients, levels of age-adjusted serum IgE, cell-bound IgE, and FcεRI correlate. Even in the absence of elevated levels of serum IgE, cell-bound IgE can be detected on peripheral blood cells in a subgroup of patients.     

Serum levels of total IgE and soluble CD23 in bronchial asthma

The aim of the present study was to compare, during the pollen season, serum levels of total IgE and soluble CD23 (sCD23) from patients with allergic bronchial asthma, with those from healthy subjects. Significantly higher levels of total IgE and sCD23 were found in patients with asthma compared to the control group. Both in normal controls and in asthmatic patients, a significant correlation was shown between the levels of these two molecules. In asthmatic patients, significant correlations were found for both total IgE and sCD23, with lung function measured as bronchial responsiveness to inhaled methacholine. These results suggest that in asthmatic patients, in addition to the study of total serum IgE levels, the assessment of sCD23 serum levels may be helpful in the evaluation of disease activity.     

Human cord blood-derived mast cells synthesize and release I-309 in response to IgE

Mast cells are the central mediating cells of allergic reactions. Binding of allergen specific IgE to high affinity IgE receptor (Fcepsilon RI) and subsequent binding of allergen by the IgE causes receptor cross-linking and activation. In a study examining the differential gene expression in human cord blood-derived mast cells (CBMCs) mediated by activation of Fcepsilon RI both with IgE and IgE followed by cross-linking with alpha-IgE, the chemokine I-309 was found to be upregulated. I-309 is the ligand for the CCR8 receptor and is responsible for chemoattraction of TH2 type T-cells. Interestingly, I-309 RNA and protein levels were elevated not only in response to IgE/alpha-IgE activation but also by IgE alone. In addition, the I-309 levels were augmented by growth of the CBMCs in the presence of the proinflammatory cytokine IL-4. GM-CSF and MIP-1alpha secretion was also induced by IgE. These results suggest that IgE, through the production and release of cytokines such as I-309, GM-CSF and MIP-1alpha could promote an inflammatory reaction in the absence of antigen stimulation of mast cells.     

Allergen-specific IgE and IgG4 are markers of resistance and susceptibility in a human intestinal nematode infection

IgG4 has been proposed to act as a 'blocking antibody' due to its ability to compete for the same epitopes as IgE thus preventing IgE-dependent allergic responses. IgG4 and IgE are both elevated in helminth infections and strong anti-parasite IgE responses are associated with resistance to infection. We wished to determine the relationship between anti-parasite IgG4 and IgE and Ascaris lumbricoides infection status. We examined anti-parasite responses, including antibody levels to recombinant Ascaris allergen-1A (rABA-1A), a target of serum IgE in endemic populations. Worm burden was indirectly estimated by measuring parasite egg output in a cross-sectional human population (N = 105). Levels of anti-parasite IgG4 and IgE in patients' plasma were quantified by immunoassay. Global anti-parasite antibody responses did not bear any significant relationships with intensity of Ascaris infection. Individuals who had detectable levels of IgE but not IgG4 to rABA-1A (11%) had lower average levels of infection compared with individuals who produced anti-rABA-1A IgG4 (40%) and sero-negative individuals (49%) (P = 0.008). The ratio of IgG4/IgE in rABA-1A responders positively correlated with intensity of infection (P < 0.025). IgG4 levels positively correlated with infection level in younger children (age 4-11) where average levels of infection were increasing (P = 0.038), whereas allergen specific IgE emerged as a correlate of immunity in older children and adults (age 12-36) where infection levels were decreasing (P = 0.048). Therefore, in a gastrointestinal helminth infection, differential regulation of anti-allergen antibody isotypes relate to infection level. Our results are consistent with the concept that IgG4 antibody can block IgE-mediated immunity and therefore allergic processes in humans.     

Allergic diseases,drug adverse reactions and total immunoglobulin E levels in lupus erythematosus patients

BACKGROUND: The association of allergic diseases, drug adverse reactions and elevated total immunoglobulin E (IgE) concentration in systemic lupus erythematosus patients remains controversial. The aim of the study was to investigate the prevalence of those features in active and inactive systemic lupus erythematosus patients, and in the control group as well. METHODS: Total IgE concentration was evaluated by enzyme-linked immunosorbent assay. RESULTS AND CONCLUSIONS: The results of our study revealed that concomitant allergic diseases were not more frequent in systemic lupus erythematosus patients than in the general population. Total IgE concentration was significantly higher during the active stage of the disease. Drug reactions were very frequent but not connected with IgE elevation. Our results indicate that IgE may play a role in lupus pathogenesis, especially in the active phase of the disease.     

Altered signaling through IL-12 receptor in children with very high serum IgE levels

An alteration of Th1/Th2 homeostasis may lead to diseases in humans. In this study, we investigated whether an impaired IL-12R signaling occurred in children with elevated serum IgE levels divided on the basis of the IgE levels (group A: >2000 kU/l; group B: <2000 kU/l). We evaluated the integrity of the IL-12R signaling through the analysis of phosphorylation/activation of STAT4, and mRNA expression and membrane assembly of the receptor chains. At a functional level, a proliferative defect of lymphocytes from group A patients was observed. In these patients, an abnormal IL-12R signaling was documented, and this finding was associated with abnormal expression of the IL-12Rβ2 chain. Our data indicate that in patients with very high IgE levels the generation of Th1 response is impaired, and that this abnormality associates with abnormal IL-12R signaling.