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Both immunoglobulin E (IgE)-mediated food allergy and food intolerance can lead to many changes in personal behaviour and health care resource use which have important economic consequences. These costs will impact directly, indirectly and intangibly on both individuals and society in general. It is important to measure the cost of illness (COI) of food allergy as a first step in developing and evaluating measures to reduce and control the burden of illness. This paper outlines a framework for assessing COI of food allergy from different viewpoints. It offers a structure for identifying the different cost impacts on allergic and nonallergic consumers, food producers and society as a whole, and for scoping, measurement and valuation of relevant costs. Within this structure, the existing literature is reviewed. This review illustrates the lack of information and clear methodology for assessing costs of food allergy. The paper concludes that there is a need for a more structured research programme to generate data essential for future evaluations of procedures and technologies for the diagnosis, treatment and management of food allergy. [ABSTRACT FROM AUTHOR]

The Heinz Karger Memorial Prize for outstanding scientific work has been awarded in 1987 to Dieter Bitter-Suermann and Jurgen Roth for their paper entitled "Monoclonal antibodies to polysialic acid reveal epitope sharing between invasive pathogenic bacteria, differentiating cells and tumor cells." The Heinz Karger memorial foundation invites submissions on "Oncogenes in cell differentiation" for the 1988 prize. Some of the conditions includes papers must represent original research of a review of original research by a scientist or group of scientists. Manuscripts must not exceed 20 typewritten pages, including illustrations, tables and bibliography.

The article focuses on the Dr. Heinz Karger Prize given by Dr. Heinz Karger Memorial Foundation which invites the submission of papers on the subjects "Antibodies With Intrinsic Biological Activity," and "Intestinal Absorption of Peptides." Manuscripts shall not exceed 20 typewritten pages, including illustrations, tables and bibliography. The winning paper will be published in English in one of the Karger journals. The Council of the Foundation will judge the papers and confer the prize.

This paper deals with the correlation of clinical scoring and serologic markers of inflammation in atopic dermatitis and psoriasis. Serum eosinophil cationic protein (ECP), soluble interleukin-2 receptor (sIL-2R), total serum IgE, IgG and IgM anti-IgE antibodies, and IgE immune complexes were evaluated in monitoring inflammatory sin diseases such as atopic dermatitis and psoriasis. Well-established clinical activity scores were used as standards in recording skin improvement under treatment in a clinical setting. Serum ECP was found to be increased in both atopic dermatitis and psoriasis patients compared to normal controls; sIL-2R and IgE immune complexes were increased only in atopics with increased only in atopics with increased serum IgE. Anti-IgE antibodies did not show any deviation in both groups of patients. There was a significant elevation of sIL-2R and IgE immune complexes and a nonsignificant elevation of ECP in high-IgE atopics in comparison to those with normal serum IgE. In both groups of patients there was a significant reduction of ECP and sIL-2R accompanying the improving skin condition. Serum IgE and the other immune parameters failed to respond. In contrast to other studies, serum ECP failed to correspond significantly with disease activity in our study. Our results showed measurable changes of ECP and sIL-2R for atopic dermatitis and/or psoriasis under treatment, but comparison to clinical scores remains difficult due to the different basis of the two systems. The only significant correlation was established for relative changes in sIL-2R and psoriasis area and intensity (PASI), a correlation which might be a useful approach in psoriasis. [ABSTRACT FROM AUTHOR]

This paper describes the identification of important allergens from the granary weevil (Sitophilus granarius) (Sg). Sera from Danish bakers whose skin prick tests were positive to extracts of Sg were screened for IgE against Sg extracts. We found that 54% (n = 66) had elevated levels of IgE (RAST classes 1-3, by luminescent immunoassay) against whole-body extracts of Sg. The specificity of patient IgE was investigated in an inhibition-dot immunoblotting assay. IgE binding was inhibited in all sera but two, thus indicating that the patients' IgE was indeed specific for the Sg extract. In crossed immunoelectrophoresis, 23 different proteins were identified. All RAST-positive sera were investigated in crossed radioimmuno-electrophoresis. At least 11 proteins in the Sg extract were capable of binding IgE. All individual sera reacted with at least four different proteins. The two most prominent allergens bound IgE from 88% and 100%, respectively, of the patients. These two are considered to be the most important allergens from Sg, and will be useful as markers in environmental immunochemical assays to detect allergens in samples from bakeries, grain stores, etc. [ABSTRACT FROM AUTHOR]

ELISA is increasingly used to measure antibodies in new circumstances. Recently, it has been applied to the measurement of IgG subclass antibodies against common antigens in early childhood. These studies have raised concerns about the specificity of some of these assays. This paper details the results of experiments which have assessed the specificity of IgG1 binding to allergens of dust mite (Dermatophagoides pteronyssinus) and ryegrass (Lolium perenne) pollen by inhibition ELISA in the sera of 2-year-old children of atopic parents. Six sera which showed binding of IgG1 to D. pteronyssinus and six to L. perenne were used. All had IgG1 antibody against ovalbumin. In the children's sera, binding to D. pteronyssinus was substantially inhibited by preincubation with the homologous antigen, but not with ovalbumin, thereby confirming the specificity of the assay. However, suppression of IgG 1 binding to L. perenne with the homologous antigen was conparatively small, and ovalbumin could cause an equivalent inhibition, indicating poor specificity. Furthermore, the level of IgG1 binding to L. perenne was closely correlated to the level of IgG1 binding to ovalbumin (r=0.98; P <0.001). When the assay was reversed, IgG1 binding to ovalbumin was only slightly inhibited by L. perenne, indicating that most antibody binding to ovalbumin was specific. Thus, binding IgG1 in both adult and child sera to D. pteronyssinus appeared to be specific, while child, but not adult, IgG1 binding to L. perenne showed poor specificity. This disparity may be due to differences in the affinities of the respective antibodies, and it illustrates the importance of determining assay specificity when making measurements in early childhood. [ABSTRACT FROM AUTHOR]

In this paper, we have determined the levels of IgG1 and IgG4 anti-IgE in the sera of 66 asthma patients suffering from mild (n= 24), moderate (n= 23), or severe (n= 19) symptoms, and 20 nonatopic, healthy subjects. The study has revealed that although asthma patients have significantly elevated levels of IgG1 and IgG4 anti-IgE antibodies, the concentration of these autoantibodies is not related to the severity of asthma. This conclusion may be related to the known heterogeneity of autoanti-IgE antibodies in terms of their ability to trigger basophil histamine release. [ABSTRACT FROM AUTHOR]

The article presents abstracts of various research papers to be presented in a conference to be held on September 14, 1993. One of the abstracts is on atopic allergy, which is causally related with selective activation of allergen-specific T helper type 2 (Th2) cells, which produce high amounts of interleukin (IL)-4 and IL-5. The aim of the study is to identify the factors, present during the differentiation of T helper cells that lead to selective outgrowth of Th2 cells. Another abstract is on neuroendocrine peptides which are involved in the regulation of effector cells of allergy. These peptides can also inhibit immunoglobuline synthesis but no data are available concerning human immunoglobulin (Ig) E. Neuroendocrine peptides endogenously modulate human in vitro IgE synthesis and represent eventually the postulated neuroendocrine arm in diseases like atopic dermatitis.

For determination of allergen-specific IgE in cell culture supernatants and other highly diluted IgE preparations a radioallergosorbent test (RAST) based on high adsorption polystyrene test tubes has been developed ("Maxisorp RAST"). Cladosporium herbarum extract was used as a model allergen but timothy grass pollen, house dust mite and dog dander showed similar results. The test showed specificities of both allergen and immunoglobulin isotype and significant correlations (r = 0.67-0.88) with established RAST procedures were found. Based on immunosorbent-purified allergen-specific IgE the estimated sensitivity was within the order of 150-300 pg allergen-specific IgE per ml. The within-assay variation was 4-9 % and the inter-assay-variation 17-29%. The Maxisorp RAST is useful as an inhibition assay for quantitating allergenic activity down to 0.1 biological units/ml of allergen extracts. [ABSTRACT FROM AUTHOR]

Serum IgE levels in healthy blood donors who had no history of atopy were measured by a paper-disc RIA and analyzed according to the donors' smoking habits. the IgE geometric mean for regular smokers was 41.7 IU/ml, which was significantly higher than that for nonsmokers (19.3 IU/ml) or rare smokers (22.7 IU/ml). Whereas 28% of smokers had IgE levels greater than 200 IU/ml none of the rare smokers or nonsmokers did. IgE levels in smokers showed a moderate inverse correlation with the degree of smoking. The mean IgE level was 189.8 IU/ml in those who smoked 1-9 cigarettes/day but only 32.8 IU/ml in those who smoked 10-19 cigarettes per day and 11.1 IU/ml in those who smoked 20 or more cigarettes/day. The number of years a person smoked did not seem to significantly influence the IgE level. The mean IgE level in ex-smokers (50.5 IU/ml) was much lower than in current light smokers but was still higher than in nonsmokers. There was a moderate inverse correlation between IgE levels and duration of cessation of smoking. Our data suggest a characteristic pattern for the influence of cigarette smoking on serum IgE level, namely, a striking rise associated with light smoking and a remarkable drop in heavy smokers, and such changes seemed reversible after the habit was stopped. Smoking status, therefore, appears to be an important consideration in interpreting serum IgE levels and in revising the "norms" of IgE levels. [ABSTRACT FROM AUTHOR]

The article focuses on the naturally occurring allergens that elicit immediate hypersensitivity reactions when combining with homologous IgE antibodies in human individuals. Data from a large number of investigations have been utilized in this presentation but reference is made only to a few selected papers summarizing the most important information in this field. The definition as well as the demonstration of the existence of an allergen depends on an immune reaction occurring in a living organism. One prominent characteristic of IgE is its property to bind to specific IgE receptors on mast cells and basophil granulocytes of the same or closely related species.

Background: Although avian coronavirus infectious bronchitis virus (IBV) and SARS‐CoV‐2 belong to different genera of the Coronaviridae family, exposure to IBV may result in the development of cross‐reactive antibodies to SARS‐CoV‐2 due to homologous epitopes. We aimed to investigate whether antibody responses to IBV cross‐react with SARS‐CoV‐2 in poultry farm personnel who are occupationally exposed to aerosolized IBV vaccines. Methods: We analyzed sera from poultry farm personnel, COVID‐19 patients, and pre‐pandemic controls. IgG levels against the SARS‐CoV‐2 antigens S1, RBD, S2, and N and peptides corresponding to the SARS‐CoV‐2 ORF3a, N, and S proteins as well as whole virus antigens of the four major S1‐genotypes 4/91, IS/1494/06, M41, and D274 of IBV were investigated by in‐house ELISAs. Moreover, live‐virus neutralization test (VNT) was performed. Results: A subgroup of poultry farm personnel showed elevated levels of specific IgG for all tested SARS‐CoV‐2 antigens compared with pre‐pandemic controls. Moreover, poultry farm personnel, COVID‐19 patients, and pre‐pandemic controls showed specific IgG antibodies against IBV strains. These antibody titers were higher in long‐term vaccine implementers. We observed a strong correlation between IBV‐specific IgG and SARS‐CoV‐2 S1‐, RBD‐, S2‐, and N‐specific IgG in poultry farm personnel compared with pre‐pandemic controls and COVID‐19 patients. However, no neutralization was observed for these cross‐reactive antibodies from poultry farm personnel using the VNT. Conclusion: We report here for the first time the detection of cross‐reactive IgG antibodies against SARS‐CoV‐2 antigens in humans exposed to IBV vaccines. These findings may be useful for further studies on the adaptive immunity against COVID‐19. [ABSTRACT FROM AUTHOR]

The article focuses on purification and characterization of atopic allergens. In the past two decades, several atopic allergens, which induce IgE antibody-mediated immediate hypersensitivity in man have been purified to near homogeneity and studied for their immunochemical properties. In this paper will be reviewed some of the general findings drawn from such studies. Allergen characterization studies with extracts from these sources have confirmed the views of allergists that all extracts are multi-allergen systems and that individuals can have varying patterns of sensitivity to different allergens.

The article provides information on meetings and seminars to be held. "Belgian Society of Allergology and Clinical Immunology," is going to held a symposium on the "Role of Immunoglobulin E in Bronchial Asthma." It is to be held at Academic Hospital, Ghent, Belgium on November 25,1978. The "Foundation for Allergy Research in Europe" bestows a Gold Medal every year for scientific work of practical clinical relevance in the field of allergy research. The topic chosen is "Standardization of Allergens."

Background: Recent studies showed that a single injection of human monoclonal allergen‐specific IgG antibodies significantly reduced allergic symptoms in birch pollen‐allergic patients. Since the production of full monoclonal antibodies in sufficient amounts is laborious and expensive, we sought to investigate if smaller recombinant allergen‐specific antibody fragments, that is, nanobodies, have similar protective potential. For this purpose, nanobodies specific for Bet v 1, the major birch pollen allergen, were generated to evaluate their efficacy to inhibit IgE‐mediated responses. Methods: A cDNA‐VHH library was constructed from a camel immunized with Bet v 1 and screened for Bet v 1 binders encoding sequences by phage display. Selected nanobodies were expressed, purified, and analyzed in regards of epitope‐specificity and affinity to Bet v 1. Furthermore, cross‐reactivity to Bet v 1‐homologues from alder, hazel and apple, and their usefulness to inhibit IgE binding and allergen‐induced basophil activation were investigated. Results: We isolated three nanobodies that recognize Bet v 1 with high affinity and cross‐react with Aln g 1 (alder) and Cor a 1 (hazel). Their epitopes were mapped to the alpha‐helix at the C‐terminus of Bet v 1. All nanobodies inhibited allergic patients' polyclonal IgE binding to Bet v 1, Aln g 1, and Cor a 1 and partially suppressed Bet v 1‐induced basophil activation. Conclusion: We identified high‐affinity Bet v 1‐specific nanobodies that recognize an important IgE epitope and reduce allergen‐induced basophil activation revealing the first proof that allergen‐specific nanobodies are useful tools for future treatment of pollen allergy. [ABSTRACT FROM AUTHOR]

Background: Evidence has accumulated that birch pollen immunotherapy reduces rhinoconjunctivitis to pollen of birch homologous trees. Therapeutic efficacy has been associated with IgE‐blocking IgG antibodies. We have recently shown that sera collected after 16 weeks of sublingual immunotherapy with recombinant Bet v 1 (rBet v 1‐SLIT) display strong IgE‐blocking bioactivity for Bet v 1. Here, we assessed whether rBet v 1‐SLIT‐induced IgG antibodies display cross‐blocking activity to related allergens in Fagales pollen. Methods: IgE, IgG1 and IgG4 reactivity to recombinant Bet v 1, Aln g 1, Car b 1, Ost c 1, Cor a 1, Fag s 1, Cas s 1 and Que a 1 were assessed in pre‐ and post‐SLIT samples of 17 individuals by ELISA. A basophil inhibition assay using stripped basophils re‐sensitized with a serum pool containing high Bet v 1‐specific IgE levels was established and used to assess CD63 expression in response to allergens after incubation with pre‐SLIT or post‐SLIT samples. IgG1 and IgG4 were depleted from post‐SLIT samples to assess its contribution to IgE‐cross‐blocking. Results: Sublingual immunotherapy with recombinant Bet v 1 boosted cross‐reactive IgE antibodies and induced IgG1 and IgG4 antibodies with inter‐ and intra‐individually differing reactivity to the homologs. Highly variable cross‐blocking activities of post‐SLIT samples to the different allergens were found. IgG1 and IgG4 antibodies displayed cross‐blocking activity with individual variance. Conclusions: Our mechanistic approach suggested that immunotherapy with the reference allergen Bet v 1 induces individual repertoires of cross‐reactive IgG1 and IgG4 antibodies. The cross‐blocking bioactivity of these antibodies was also highly variable and neither predictable from protein homology nor IgE‐cross‐reactivity. [ABSTRACT FROM AUTHOR]

Four allergologically important fungi, viz. Aspergillus fumigatus, Penicillium notalum Alternaria altermata, and Cladosporium herbarum were cultured in a liquid synthetic me with or without addition of 0.1 % yeast extract (YE). After 10 and 28 days of cultivation, immunochemical properties of the fungal extracts, characterised by precipitation pattern and IgG- and IgE-binding capacity, were studied. In pure synthetic medium no large differences were observed in number of precipitates, as measured by DID, among the four antigenic fractions of each fungus (metabolic and mycelial antigens of both early and late phase cultures). Addition of YE to the growth medium hardly changed the number of precipitates and generally caused a decrease in lgG-binding capacity of the extracts. In contrast to these observations were the findings with the IgE-binding capacities of the fungal extracts as measured by RAST. Most allergenic fractions demonstrated an increase (sometimes strong) in lgE-binding capacity after YE was added to the growth medium. It is concluded that the time of cultivation influences the immunochemical characteristics of fungal extracts and that mycelial as well as metabolic antigens of both early and late phase cultures should be used in order to obtain a wide spectrum of allergens in extracts used for diagnostic purposes. [ABSTRACT FROM AUTHOR]

The article focuses on the standardization of biological methods in clinical work in allergy. For several allergens in the IgE-dependent systems, biological and laboratory methods are available which correlate fairly well with each other when adequately performed and which are suggested should be used together to express the total diagnostic potency of allergen extracts. The specificity of the skin test for quantitation of the total allergenic activity of extracts for diagnosis appears to be accepted. Similar standardization of allergen preparations meant for immunotherapy is, however, likely to raise a quite lively debate.

IgE and IgG antibodies (ab) and lymphocyte transformation (LT) were studied in untreated and hyposensitized birch pollen allergic subjects and in non-a topic controls using whole extract and fractions obtained by gel filtration of birch pollen extract. All the allergic subjects had positive IgE ab, IgG ab and LT responses to the whole extract. Both the untreated and the hyposensitized subjects had peak IgE ab and LT responses against the allergenic fractions of the extract, while negative responses were obtained in the non-atopic controls. Only hyposensitized subjects had developed high IgG ab responses to the allergenic fractions. Most of the treated and untreated subjects showed IgG ab and LT responses to the high molecular weight fractions with low allergenic activity. Significantly higher IgE ab responses to these fractions were observed in the treated subjects than in the untreated ones, indicating potentiation of IgE ab responses against some antigens during immunotherapy. Some of the allergic subjects also responded to the fractions of low molecular size (mol.wt. 2000-5000) with low allergenic activity. Both IgE ab, IgG ab and LT responses to these fractions were observed. [ABSTRACT FROM AUTHOR]

The radioallergosorbent test (RAST) was used to demonstrate IgE antibodies to Cladosporium herbarum in 35 children. Freeze-dried samples of Cladosporium herbarum were obtained from two commercial producers, extracted and used for the preparation of two RAST disc series which were compared with the commercially available Phadebas Cladoiponum herbarum discs. Marked qualitative differences were found. [ABSTRACT FROM AUTHOR]

Background: The missing asymptomatic COVID‐19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic. Measure: Utilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11 766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. Sixty‐three healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS‐CoV‐2 proteome microarray, and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset. Results: A combination test of NAT and serological testing for IgM antibody discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS‐CoV‐2. Different from strong and persistent N‐specific antibodies, S1‐specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17 days to 25 days, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months. Conclusion: Our findings might have important implications for the definition of asymptomatic COVID‐19 infections, diagnosis, serological survey, public health, and immunization strategies. [ABSTRACT FROM AUTHOR]

Background: Egg‐white ovomucoid, that is, Gal d 1, is associated with IgE‐mediated allergic reactions in most egg‐allergic children. Epitope‐specific IgE levels have been correlated with the severity of egg allergy, while emerging evidence suggests that other antibody isotypes (IgG1, IgG4, IgA, and IgD) may have a protective function; yet, their epitope‐specific repertoires and associations with atopic comorbidities have not been studied. Methods: Bead‐based epitope assay (BBEA) was used to quantitate the levels of epitope‐specific (es)IgA, esIgE, esIgD, esIgG1, and esIgG4 antibodies directed at 58 (15‐mer) overlapping peptides, covering the entire sequence of ovomucoid, in plasma of 38 egg‐allergic and 6 atopic children. Intraclass correlation (ICC) and coefficient of variation (CV) were used for the reliability assessment. The relationships across esIgs were evaluated using network analysis; linear and logistic regressions were used to compare groups based on egg allergy status and comorbidities. Results: BBEA had high reliability (ICC >0.75) and low variability (CV <20%) and could detect known IgE‐binding epitopes. Egg‐allergic children had lower esIgA1 (P =.010) and esIgG1 (P =.016) and higher esIgE (P <.001) and esIgD (P =.015) levels compared to the atopic controls. Interestingly, within the allergic group, children with higher esIgD had decreased odds of anaphylactic reactions (OR =0.48, P =.038). Network analysis identified most associations between esIgE with either esIgG4 or esIgD; indicating that IgE‐secreting plasma cells could originate from either sequential isotype switch from antigen‐experienced intermediate isotypes or directly from the IgD+ B cells. Conclusions: Collectively, these data point toward a contribution of epitope‐specific antibody repertoires to the pathogenesis of egg allergy. [ABSTRACT FROM AUTHOR]

This article presents abstracts of several manuscripts related to allergic diseases and medicine. According to one abstract, the paper describes a quantitative radioimmunoassay for IgE antibodies. According to another abstract, the paper studies the efficacy of preventing the development of serious otitis media by using an oral decongestant. In association with this article, in a randomized double-blind study, 190 children were treated for acute otitis media with antibiotics and either pseudoephedrine hydrochloride or placebo.

Background: Omalizumab, a humanized recombinant monoclonal anti‐IgE antibody, proved to be effective in patients with chronic spontaneous urticaria (CSU), including severe and treatment‐refractory CSU. Here, we report omalizumab's effect on gene expression in skin biopsies from CSU patients enrolled in a double‐blind, placebo‐controlled study. Methods: Chronic spontaneous urticaria patients (18‐75 years) were randomized to either 300 mg omalizumab (n = 20) or placebo (n = 10) administered s.c. every 4 weeks for 12 weeks (NCT01599637). Lesional and nonlesional skin biopsies were collected from the same area of consenting patients and assessed at baseline and on Day 85 compared with skin biopsies from the same area of 10 untreated healthy volunteers (HVs). Gene expression data were generated using Affymetrix HG‐U133Plus2.0 microarrays. Statistical analyses were performed using R packages. Results: At baseline, 63 transcripts were differentially expressed between lesional and nonlesional skin. Two‐thirds of these lesional signatures were also differentially expressed between lesional and HV skin. Upon treatment with omalizumab, >75% of lesional signatures changed to reflect nonlesional skin expression levels (different vs placebo, P < 0.01). Transcripts upregulated in lesional skin (vs nonlesional and/or HV skin) suggested increased mast cell/leukocyte infiltration (FCER1G, C3AR1, CD93, S100A8, and S100A9), increased oxidative stress, vascularization (CYR61), and skin repair events (KRT6A, KRT16). Lesional signatures were not modulated by treatment in nonresponders (defined based on UAS7 longitudinal changes ≥16). Conclusion: Omalizumab, in treatment responders, reverted transcriptional signatures associated with CSU lesion phenotype to reflect nonlesional/HV expression levels; this is consistent with observed omalizumab‐mediated clinical improvement observed in patients with CSU. The gene expression of the lesional skin of patients with chronic spontaneous urticaria shows a distinct signature when compared to their nonlesional skin and the skin of healthy volunteers. The pattern of gene expression in the lesional skin of omalizumab‐treated patients are different than before treatment, but not in their nonlesional skin. In treatment responders, omalizumab treatment shows reverted transcriptional signatures associated with CSU lesion phenotype to reflect nonlesional/healthy volunteer expression levels consistent with observed clinical improvement. [ABSTRACT FROM AUTHOR]

Abstract: Background: Profilins are dominant pan‐allergens known to cause cross‐sensitization, leading to clinical symptoms such as pollen‐food syndrome. This study aimed to determine the T‐cell response to Phl p 12 in profilin‐sensitized patients, by measuring the prevalence, strength and cross‐reactivity to clinically relevant profilins. Methods: The release of Phl p allergens from pollen was determined by mass spectrometry and immunochemistry. T‐cell responses, epitope mapping and cross‐reactivity to profilins (Phl p 12, Ole e 2, Bet v 2 and Mal d 4) were measured in vitro using PBMCs from 26 Spanish grass‐allergic donors IgE‐sensitized to profilin. Cross‐reactivity was addressed in vivo using 2 different mouse strains (BALB/c and C3H). Results: Phl p 12 and Phl p 1 are released from pollen simultaneously and in similar amounts. Both T‐cell response frequency (17/26 donors) and strength were comparable between Phl p 12 and Phl p 1. T‐cell cross‐reactivity to other profilins correlated with overall sequence homology, and 2 immunodominant epitope regions of Phl p 12 were identified. Data from mice immunized with Phl p 12 showed that cross‐reactivity to Bet v 2 was mediated by conserved epitopes and further influenced by additional genetic factors, likely to be MHC II. Conclusion: The strength, prevalence and cross‐reactivity of T‐cell responses towards Phl p 12 are comparable to the major allergen Phl p 1, which supports the hypothesis that T cells to Phl p 12 can play an important role in development of allergic symptoms, such as those associated with pollen‐food syndrome. [ABSTRACT FROM AUTHOR]

Abstract: Background: Allergen‐specific immunotherapy (AIT) induces specific blocking antibodies (Ab), which are claimed to prevent IgE‐mediated reactions to allergens. Additionally, AIT modulates cellular responses to allergens, for example, by desensitizing effector cells, inducing regulatory T and B lymphocytes and immune deviation. It is still enigmatic which of these mechanisms mediate(s) clinical tolerance. We sought to address the role of AIT‐induced blocking Ab separately from cellular responses in a chimeric human/mouse model of respiratory allergy. Methods: Nonobese diabetic severe combined immunodeficient γc−/− (NSG) mice received intraperitoneally allergen‐reactive PBMC from birch pollen‐allergic patients together with birch pollen extract and human IL‐4. Engraftment was assessed by flow cytometry. Airway hyperresponsiveness (AHR) and bronchial inflammation were analyzed after intranasal challenges with allergen or PBS. Sera collected from patients before and during AIT with birch pollen were added to the allergen prior to intranasal challenge. The IgE‐blocking activity of post‐AIT sera was assessed in vitro. Results: Human cells were detected in cell suspensions of murine lungs and spleens indicating successful humanization. Humanized mice displayed a more pronounced AHR and bronchial inflammation when challenged with allergen compared to negative controls. Post‐AIT sera exerted IgE‐blocking activity. In contrast to pre‐AIT sera, the presence of heterologous and autologous post‐AIT sera significantly reduced the allergic airway inflammation and matched their IgE‐blocking activity determined in vitro. Conclusion: Our data demonstrate that post‐AIT sera with IgE‐blocking activity ameliorate allergic airway inflammation in a human/mouse chimeric model of respiratory allergy independently of AIT‐induced cellular changes. [ABSTRACT FROM AUTHOR]

Patients with chronic spontaneous urticaria ( CSU) are widely held to often have other autoimmune disorders, including autoimmune thyroid disease. Here, we systematically evaluated the literature on the prevalence of thyroid autoimmunity in CSU and vice versa. There is a strong link between CSU and elevated levels of IgG antithyroid autoantibodies ( AAbs), with most of a large number of studies reporting rates of ≥10%. Levels of IgG against thyroid peroxidase ( TPO) are more often elevated in CSU than those of other IgG antithyroid AAbs (strong evidence). Levels of IgG antithyroid AAbs are more often elevated in adult patients with CSU than in children (strong evidence). Patients with CSU exhibit significantly higher levels of IgG antithyroid AAbs (strong evidence) and IgE-anti- TPO (weak evidence) than controls. Elevated IgG antithyroid AAbs in CSU are linked to the use of glucocorticoids (weak evidence) but not to disease duration or severity/activity, gender, age, or ASST response (inconsistent evidence). Thyroid dysfunction rates are increased in patients with CSU (strong evidence). Hypothyroidism and Hashimoto's thyroiditis are more common than hyperthyroidism and Graves' disease (strong evidence). Thyroid dysfunction is more common in adult patients with CSU than in children (strong evidence) and in female than in male patients with CSU (weak evidence). Urticaria including CSU is more prevalent in patients with thyroid autoimmunity than in controls (weak evidence). CSU can improve in response to treatment with levothyroxine or other thyroid drugs (strong evidence). Pathogenic mechanisms in CSU patients with thyroid autoimmunity may include IgE against autoantigens, immune complexes, and complement. [ABSTRACT FROM AUTHOR]

When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions ( DHRs) before showing the evidence of either drug-specific antibodies or T cells. DHRs may be allergic or nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life-threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under-reporting) and overdiagnosis (due to an overuse of the term 'allergy') are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more-expensive or less-effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class-induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (i CAALL), formed by the European Academy of Allergy and Clinical Immunology ( EAACI), the American Academy of Allergy, Asthma and Immunology ( AAAAI), the American College of Allergy, Asthma and Immunology ( ACAAI), and the World Allergy Organization ( WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs. [ABSTRACT FROM AUTHOR]

Background The fine balance of immunoglobulins ( Ig) E, Ig G1, Ig G4 and Ig A in healthy production is maintained by the interaction of B cells with adaptive and innate immune response. The regulation of toll-like receptors ( TLRs)-driven innate and adaptive immune effector B-cell response and the role of mammalian telomeric TTAGGG repeat elements represent an important research area. Methods Human PBMC and purified naive and memory B cells were stimulated with specific ligands for TLR2, TLR3, TLR4, TLR5, TLR7, TLR8 and TLR9 in the presence or absence of telomeric oligonucleotides. B-cell proliferation, differentiation and antibody production were determined. Results TLR9 ligand directly activates naive and memory B cells, whereas TLR7 can stimulate them in the presence of plasmacytoid dendritic cells. Human B cells proliferate and turn into antibody-secreting cells in response to TLR3, TLR7 and TLR9, but not to TLR2, TLR4, TLR5 and TLR8 ligands. Stimulation of B cells with intracellular TLR3, TLR7 and TLR9 induced an activation cascade leading to memory B-cell generation and particularly Ig G1, but also Ig A, Ig G4 and very low levels of Ig E production. Mammalian telomeric oligodeoxynucleotide ( ODN) significantly inhibited all features of TLR ligand-induced events in B cells including B-cell proliferation, Ig E, Ig G1, Ig G4, Ig A production, class switch recombination, plasma cell differentiation induced by TLR3, TLR7 and TLR9 ligands. Conclusion B cells require specific TLR stimulation, T-cell and plasmacytoid dendritic cell help for distinct activation and Ig production profiles. Host-derived telomeric ODN suppress B-cell activation and antibody production demonstrating a natural mechanism for the control of overexuberant B-cell activation, antibody production and generation of memory. [ABSTRACT FROM AUTHOR]

Background Lipids are required for mice sensitization to Ber e 1, Brazil nut major allergen. Here, we characterized different lipid fractions extracted from Brazil nuts and the lipid-binding ability of Ber e 1. Further, we determined their in vivo ability to induce Ber-specific anaphylactic antibodies and the role of invariant natural killer T (i NKT) cells in this process. Methods Wild-type ( WT) and i NKT cell-deficient mice were sensitized with Ber e 1 and specific lipid fractions, and anaphylactic antibodies were measured by enzyme-linked immunosorbent assay ( ELISA) and passive cutaneous anaphylaxis ( PCA). The lipid-binding characteristic of Ber e 1 ( Ber) was established by using fluorescent probes and 15 N-labeled NMR. In vitro production of IL-4 was determined in Ber/lipid C-stimulated mouse i NKT cells and human T-cell lines containing NKTs primed with CD1d+ C1 R transfectants by flow cytometry and ELISA, respectively. Results Only one specific lipid fraction (lipid C), containing neutral and common phospholipids, induced Ber anaphylactic antibodies in mice. Ber e 1 has a lipid-binding site, and our results indicated an interaction between Ber e 1 and lipid C. i NKT-deficient mice produced lower levels of anaphylactic antibodies than WT mice. In vitro, Ber/lipid C-stimulated murine i NKT cells produced IL-4 but not IFN-gamma. Human T-cell lines derived from nut-allergic patients produced IL-4 to Ber/lipid C in a CD1d− and dose-dependent manner. Conclusion Lipid fraction C from Brazil nut presents an essential adjuvant activity to Ber e 1 sensitization, and i NKT cells play a critical role in the development of Brazil nut-allergic response. [ABSTRACT FROM AUTHOR]

Background IL-17 A is associated with different asthma phenotypes as virus-associated or steroid-resistant asthma. Invariant natural killer T ( iNKT) cells play an important role in the pathogenesis of asthma. The aim of the study was to evaluate the activity of polyinosinic-polycytidylic acid [poly( I: C)] on IL-17 A production by CD1d-activated iNKT cells. Methods We analysed the in vitro effect of poly( I: C) on the release of IL-17 A by spleen and lung CD1d-activated iNKT cells with α-galactosylceramide (α- Gal Cer). Its activity was also investigated in an α- Gal Cer-induced murine models, including lung inflammation. The inhibition of IL-17 A by Toll-like receptor ( TLR) 7 agonists in the same in vitro and in vivo models has been analysed. Results Poly( I: C) upregulated the in vitro IL-17 A production by CD1d-activated NK1.1− CD4− iNKT subset, without modifying type 1 and type 2 cytokines. The two stimuli selectively upregulated IL-17A serum levels in vivo. Their intratracheal administration resulted in increased airway hyper-reactivity ( AHR), neutrophilia in bronchoalveolar lavage and airway inflammation, which were inhibited by anti- IL-17 A antibody. Poly( I: C) effects were attributable to IL1β and IL-23 release from dendritic cells, as showed by inhibition with neutralizing antibodies. TLR7 agonists inhibited the IL-17A production by poly( I: C) plus α- Gal Cer in the same models. Such effect was associated with the increased production by DC of IL-17 A-inhibiting cytokines and the dampening of IL-1β and IL-23. Conclusions Synthetic ds RNA selectively expand a CD1d-driven IL-17 A-producing iNKT cell subset, thus explaining the worsening of airway inflammation by some viral infections. TLR3- and TLR7-triggering viral sequences can exert variable and opposite effects on adaptive immune response. [ABSTRACT FROM AUTHOR]

Background Free light chain ( FLC) concentrations are demonstrated to be increased in different inflammatory disorders and are proposed to mediate mast cell-dependent immune responses. A role for mast cells is suggested in chronic rhinosinusitis with nasal polyposis ( CRSw NP), which is characterized by a local Th2 inflammatory response. However, clear mast cell-activating factors are not always apparent. In this study, the presence of FLCs in CRS patients with or without nasal polyps ( CRSw/ sNP) was investigated and the effect of different treatments on FLC expression was analyzed. Methods Nasal tissue, nasal secretion, and serum of control patients, patients with CRSw NP, and CRSs NP were analyzed for the presence of kappa and lambda FLC. The expression of FLCs in nasal polyp tissue was investigated using immunohistochemistry. In addition, FLC was measured in serum and nasal secretion of nasal polyp patients treated with methylprednisolone, doxycycline, anti- IL-5, or placebo. Results Free light chain concentrations were increased in nasal secretion and mucosal tissue homogenates in patients with chronic rhinosinusitis, and this effect was most prominent in CRSw NP patients. Immunohistochemical analysis confirmed the increased FLC concentrations in nasal polyp tissue. In CRSw NP patients, treatment with methylprednisolone or anti- IL-5 resulted in the reduction in systemic or local FLC concentrations, respectively. Conclusion The presence of FLC in CRSw NP and CRSs NP suggests a possible role in mediating the local immune reaction in the paranasal cavities. Furthermore, the decrease in local FLCs after treatment with anti- IL-5 presumes that IL-5 creates an environment that favors FLC production. [ABSTRACT FROM AUTHOR]

To cite this article: Aalberse RC, Crameri R. IgE-binding epitopes: a reappraisal. Allergy 2011; 66: 1261-1274. Abstract Here, we discuss various questions related to IgE epitopes: What are the technical possibilities and pitfalls, what is currently known, how can we put this information into hypothetical frameworks and the unavoidable question: how useful is this information for patient care or allergenicity prediction? We discuss the information obtained by (i) 3D structures of allergen-antibody complexes; (ii) analysis of allergen analogues; (iii) mimics without obvious structural similarity; (iv) mAbs competing with IgE; (v) repertoire analysis of cloned IgEs, and other developments. Based on limited data, four suggestions are presented in the literature: (i) IgE might be more cross-reactive than IgG; (ii) IgE might be more often directed to immunologically 'uninviting' surfaces; (iii) IgE epitopes may tend to cluster and (iv) IgE paratopes might have a higher intrinsic flexibility. While these are not proven facts, they still can generate hypotheses for future research. The hypothesis is put forward that the IgE repertoire of switched B-cells is less influenced by positive selection, because positive selection might not be able to rescue IgE-switched B cells. While this might be of interest for the discussion about mechanisms leading to allergen-sensitization, we need to be modest in answering the 'clinical relevance' question. Current evidence indicates the IgE-epitope repertoire is too big to make specific IgE epitopes a realistic target for diagnosis, treatment or allergenicity prediction. In-depth analysis of a few selected IgE epitope-peptides or mimitopes derived from allergen-sequences and from random peptide libraries, respectively, might well prove rewarding in relation to diagnosis and prognosis of allergy, particularly food allergy. [ABSTRACT FROM AUTHOR]

Background: The modified Th2 response, defined as an IgG4 response in the absence of IgE, is suggested to protect against the development of allergic sensitization. However, studies suggesting this protective effect all had a cross-sectional design, making it impossible to study the development of both responses. Aim of the study: We aimed to study the dynamics in IgG4 antibodies in relation to allergic sensitization in an occupational cohort of starting laboratory animal workers. Moreover, we studied the relation between exposure, antibody responses, atopy and self reported allergic symptoms. Methods: A total of 110 starting animal workers were followed for 2 years. IgG4 antibodies against rats and mice were assessed. Workers were tested for allergic sensitization and exposure to animal allergens was estimated. Symptom status was assessed using questionnaires. Results: Rat and mouse specific IgG4 antibodies were present before the development of allergy and did not significantly change over time. Allergic sensitization was related to exposure and atopic status but high levels of IgG4 showed no protective effect. In contrary, workers that developed mouse specific sensitization during follow up had higher levels of mouse specific IgG4. Symptoms were related to allergic sensitization and IgG4 levels did not influence that relationship. Conclusions: IgG4 antibodies are present before IgE antibodies develop and IgG4 levels are stable over time. In our occupational cohort, the modified Th2 response had no protective effect on development of sensitization or allergic symptoms. [ABSTRACT FROM AUTHOR]

To cite this article: Lødrup Carlsen KC, Söderström L, Mowinckel P, Håland G, Pettersen M, Munthe Kaas MC, Devulapalli CS, Buchmann M, Ahlstedt S, Carlsen K-H. Asthma prediction in school children; the value of combined IgE-antibodies and obstructive airways disease severity score. Allergy 2010; 65: 1134–1140. Background: Allergic sensitisation increases the risk for asthma development. In this prospective birth cohort (Environment and Childhood Asthma) study, we hypothesized that combining quantitative measures of IgE antibodies (Σ-IgE) and Severity score of obstructive airways disease (OAD) at 2 years of age (Severity score) is superior to predict current asthma (CA) at 10 years than either measure alone. Secondarily, we assessed if gender modified the prediction of CA. Methods: A follow-up study at 10 years of age was performed in 371 2-year-old children with recurrent ( n = 219) or no ( n = 152) bronchial obstruction with available serum analysed for Σ-IgE to common food and inhalant allergens through a panel test, Phadiatop Infant® (Phadia, Uppsala, Sweden). Clinical variables included allergic sensitisation and exercise testing to characterise children with CA vs not CA at 10 years and the Severity score (0–12, 0 indicating no OAD) was used to assess risk modification. Results: Severity score alone explained 24% (Nagelkerke R2 = 0.24) of the variation in CA, whereas Σ-IgE explained only 6% ( R2 = 0.06). Combining the two increased the explanatory capacity to R2 = 0.30. Gender interacted significantly with Σ-IgE; whereas Severity score predicted CA in both genders, the predictive capacity of Σ-IgE for CA at 10 years was significant in boys only. Conclusion: Combining Σ-IgE to inhalant allergens and Severity score at 2 years was superior to predict asthma at 10 years than either alone. Severity score predicted CA in both genders, whereas Σ-IgE significantly predicted CA in boys only. [ABSTRACT FROM AUTHOR]

To cite this article: Zhao C-Q, Li T-L, He S-H, Chen X, An Y-F, Wu W-K, Zhou X-H, Li P, Yang P-C. Specific immunotherapy suppresses Th2 responses via modulating TIM1/TIM4 interaction on dendritic cells. Allergy 2010; 65: 986–995 Background: Specific immunotherapy (SIT) is the only curable remedy for allergic disorders currently; however, the underlying mechanism is not fully understood yet. This study aimed to elucidate the mechanism of SIT on suppressing TIM4 (T cell immunoglobulin mucin domain molecule 4) expression in dendritic cells (DCs) and modulating the skewed T helper 2 (Th2) responses in patients with airway allergy. Methods: Twenty patients with allergic rhinitis (AR) were treated with SIT for 3 months. Before and after SIT, the expression of TIM4 in peripheral DC and TIM1 in Th2 cells was examined. The role of Fc gamma receptor (FcγR) I and II in modulating the expression of TIM4 in DCs was investigated. Results: The interaction of TIM1/TIM4 played a critical role in sustaining the polarization status of Th2 cells in AR patients. Cross-linking FcγRI by antigen/IgG complexes increased the production of TIM4 by dendritic cells via upregulating tumor necrosis factor-alpha in DCs. Exposure to microbial products promoted the expression of FcγRI in DCs that further increased the expression of TIM4. Exposure to specific antigens alone upregulated the expression of FcγRII in DCs, that suppressed the expression of TIM4. Conclusions: We conclude that SIT suppresses the skewed Th2 responses via disrupting the interaction of TIM1/TIM4 in antigen-specific Th2 cells. [ABSTRACT FROM AUTHOR]

Hypersensitivity reactions to betalactams (BLs) are classified as immediate or nonimmediate. The former usually appear within 1 h of drug-intake and are mediated by specific IgE-antibodies. Nonimmediate reactions are those occurring more than 1 h after drug-intake, and they can be T-cell mediated. The diagnostic evaluation of allergic reactions to BLs has changed over the last 5 years, for several reasons. Major and minor determinants are no longer commercially available for skin testing in many countries. In immediate allergic reactions, the sensitivity of skin testing and immunoassays is decreasing and new in vitro methods, such as the basophil activation test, are gaining importance for diagnosis. For nonimmediate reactions, skin testing appears to be less sensitive than previous results, although more studies need to be carried out in this direction. Nevertheless, the drug provocation test is still necessary for diagnosis. [ABSTRACT FROM AUTHOR]

Background: Wheat and rye flours are among the most important allergens causing occupational asthma. Usually, the diagnosis of baker’s asthma is based on inhalation challenge tests with flours. Aims of the study: To evaluate the relevance of flour-specific serum immunoglobulin E (IgE) and skin prick test (SPT) in the diagnosis of baker’s asthma and to define flour-specific IgE concentrations and wheal sizes that allow a prediction of the outcome of challenge testing. Methods: Bronchial and nasal challenge tests with wheat (rye) flour were performed in 71 (95) symptomatic bakers. Determinations of flour-specific IgE as well as SPTs were performed in all subjects. Analyses included the calculation of sensitivity, specificity, positive (PPV) and negative predictive values (NPV) at different IgE concentrations and different wheal sizes, and receiver-operating characteristics (ROC) plots with the challenge result as gold standard. Results: Thirty-seven bakers were positive in the challenge with wheat flour, while 63 were positive with rye flour. Depending on the flour-specific IgE concentrations (wheal size), PPV was 74–100% (74–100%) for wheat and 82–100% (91–100%) for rye flour, respectively. The minimal cut-off values with a PPV of 100% were 2.32 kU/l (5.0 mm) for wheat flour and 9.64 kU/l (4.5 mm) for rye flour. The shapes of the ROC plots were similar for wheat and rye flour. Conclusion: High concentrations of flour-specific IgE and clear SPT results in symptomatic bakers are good predictors for a positive challenge test. Challenge tests with flours may be avoided in strongly sensitized bakers. [ABSTRACT FROM AUTHOR]

Serological tests for immunoglobulin G4 (IgG4) against foods are persistently promoted for the diagnosis of food-induced hypersensitivity. Since many patients believe that their symptoms are related to food ingestion without diagnostic confirmation of a causal relationship, tests for food-specific IgG4 represent a growing market. Testing for blood IgG4 against different foods is performed with large-scale screening for hundreds of food items by enzyme-linked immunosorbent assay-type and radioallergosorbent-type assays in young children, adolescents and adults. However, many serum samples show positive IgG4 results without corresponding clinical symptoms. These findings, combined with the lack of convincing evidence for histamine-releasing properties of IgG4 in humans, and lack of any controlled studies on the diagnostic value of IgG4 testing in food allergy, do not provide any basis for the hypothesis that food-specific IgG4 should be attributed with an effector role in food hypersensitivity. In contrast to the disputed beliefs, IgG4 against foods indicates that the organism has been repeatedly exposed to food components, recognized as foreign proteins by the immune system. Its presence should not be considered as a factor which induces hypersensitivity, but rather as an indicator for immunological tolerance, linked to the activity of regulatory T cells. In conclusion, food-specific IgG4 does not indicate (imminent) food allergy or intolerance, but rather a physiological response of the immune system after exposition to food components. Therefore, testing of IgG4 to foods is considered as irrelevant for the laboratory work-up of food allergy or intolerance and should not be performed in case of food-related complaints. [ABSTRACT FROM AUTHOR]

Background: The clinical relevance of immunoglobulin E (IgE) to plant glycans is a longstanding debate. We sought to evaluate their clinical reactivity using the human glycoprotein lactoferrin expressed in rice. Methods: Allergic patients with IgE antibodies against plant glycans were analyzed for the presence of IgE against rice-produced lactoferrin. The potency of IgE to induce mediator release was assessed by basophil histamine release and skin prick tests (SPTs). Clinical relevance was evaluated by double-blind placebo-controlled oral challenge (DBPCOC). Results: Twenty-four of 29 sera (82.7%) with IgE antibodies against plant glycans demonstrated IgE binding to transgenic lactoferrin. In three of five cases transgenic lactoferrin induced histamine release. Compared to a control major grass pollen allergen lactoferrin concentrations needed for biological activity of IgE were 5–6 orders of magnitude higher. Skin prick test and DBPCOC were negative in five patients with potential clinical reactivity that volunteered to undergo these in vivo challenges. Conclusions: Poor or no biological activity and lack of clinical relevance of IgE-binding plant glycans (five out of five) was demonstrated using human lactoferrin expressed in rice as a model. [ABSTRACT FROM AUTHOR]

Background: Foods not commonly consumed in the European Union must be proven safe before being brought to market, including an assessment of allergenicity. We present a three-stepwise strategy for allergenicity assessment of natural novel foods using three novel vegetables, namely, water spinach, hyacinth bean, Ethiopian eggplant. Methods: First, vegetable extracts were analyzed for the presence of pan-allergens [Bet v 1 homologous proteins, profilins, nonspecific lipid transfer proteins (LTP)] by immunoblot analysis with specific animal antibodies. Secondly, the IgE-binding of the food extracts was investigated by EAST (Enzyme-allergosorbent test) and immunoblot analysis using sera with IgE-reactivity to known pan-allergens or to phylogenetically related foods from subjects (i) allergic to birch, grass and mugwort pollen, (ii) with food allergy to soy, peanut, tomato, multiple pollen-related foods and (iii) sensitized to LTP. Thirdly, the clinical relevance of IgE-binding was assessed in vivo by skin prick testing (SPT) and open oral food challenges (OFC). Results: Profilin and LTP were detected by animal antibodies in all vegetables, a Bet v 1 homologue selectively in hyacinth bean. IgE-binding to LTP, profilin and a Bet v 1 homologue was proven by immunoblot analysis and EAST. Positive SPT and OFC results were observed for all vegetables in pollen-allergic patients. Conclusions: Our stepwise procedure confirmed the presence and IgE-binding capacity of novel vegetable proteins homologous to known allergens in endemic vegetable foods. In vivo testing proved the potential of the novel vegetables to elicit clinical allergy. Hence, our described algorithm seems to be applicable for allergenicity testing of natural novel foods. [ABSTRACT FROM AUTHOR]

Background: Approximately two-thirds of egg-allergic infants become tolerant within the first 5 years of life. Objective: We sought (1) to compare the recognition of sequential (linear) and conformational binding sites of ovomucoid, ovalbumin and ovotransferrin, by IgE antibodies of children with persistent and transient egg allergy, (2) to identify immunodominant IgE-and IgG-binding epitopes of ovomucoid, and (3) to compare epitope-specificity of IgE antibodies between patients with differing natural histories of egg allergy. Methods: Using immunodot-blots or ImmunoCAPs, IgE-antibodies against conformational (native) and sequential (reduced and alkylated) egg proteins were determined at the time of clinical reactivity in patients who retained their allergy and in those who developed clinical tolerance. IgE- and IgG-binding epitopes were mapped for ovomucoid using overlapping decapeptides on SPOTs membranes. Recognition of the major IgE-binding epitopes were compared between patients with differing natural histories of egg allergy. Results: The patients with long-lasting egg allergy had a higher concentrations of IgE antibodies against sequential and native ovomucoid and ovalbumin than the children who subsequently gained tolerance ( P < 0.01). Four major IgE-binding epitopes were identified in ovomucoid at amino acid 1–10, 9–20, 47–56, and 113–124. IgE antibodies of all seven patients with persistent egg allergy recognized these epitopes whereas none of the 11 children who outgrew their egg allergy did so. Conclusions: Patients with persistent egg allergy develop IgE antibodies against more sequential and conformational epitopes of ovomucoid and ovalbumin. The presence of serum IgE antibodies to specific sequential epitopes of ovomucoid may be used as a screening instrument for persistent egg allergy. [ABSTRACT FROM AUTHOR]

Specific allergen immunotherapy has been widely practised for almost 100 years. Whilst this approach is disease-modifying and efficacious, the use of whole allergen preparations is associated with an unacceptably high prevalence of allergic adverse events during treatment. Many approaches to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity are under development. One such approach is the use of short synthetic peptides which represent major T-cell epitopes of the allergen. Major potential advantages of this approach include markedly reduced capacity to cross-link immunoglobulin-E and activate mast cells and basophils, and ease of manufacture and standardization. Promising results in preclinical studies have led to the translation of this approach to clinical studies in humans. Peptide immunotherapy is currently under development for allergic and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Physicians predominantly rely upon quantification of serum-specific immunoglobulin E (IgE) and/or skin test to confirm clinically suspected IgE-mediated allergy. However, for various reasons, identification of the offending allergen(s) and potentially cross-reactive structures is not always straightforward. Flow-assisted allergy diagnosis relies upon quantification of alterations in the expression of particular basophilic activation markers. Actually, upon challenge with a specific allergen, basophils not only secrete quantifiable bioactive mediators but also upregulate the expression of different markers which can be detected efficiently by flow cytometry using specific monoclonal antibodies. Currently, the technique has been applied in the investigation of IgE-mediated allergy caused by classical inhalant allergens, food, Hevea latex, hymenoptera venoms and drugs. It is also appreciated; the technique proves valuable in the diagnosis of non-IgE-mediated (anaphylactoid) reactions such drug hypersensitivity and the detection of autoantibodies in certain forms of chronic urticaria. This review will not address immunologic features, characteristics and general pitfalls of flow-assisted analysis of in vitro-activated basophils as summarized elsewhere. After a recapitulation of the principles and some specific technical issues of flow-assisted analysis of in vitro-activated basophils, we principally focus on the current clinical and research applications of the basophil activation tests. Personal experience of both research groups is provided, where appropriate. Finally, a viewpoint on how the field might evolve in the following years is provided. [ABSTRACT FROM AUTHOR]

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a disease with growing impact on everyday medical practice, as its prevalence has steadily increased during the last decades. Immunoglobulin-E (IgE)-mediated airway inflammation may manifest itself as AR, asthma or both. Allergic inflammation in upper and lower airways is now considered as one airway disease, with manifestation of symptoms in upper, lower or global airway. This insight into allergic inflammation of the whole respiratory tract has consequences for the diagnostic and therapeutic approach of affected patients, as highlighted in the ARIA document. In contrast to asthma, the link between AR and associated conditions in the upper airways like rhinosinusitis, nasal polyps, recurrent viral infections, adenoid hypertrophy, tubal dysfunction, otitis media with effusion and laryngitis remains less explored. It is however of utmost importance to consider the aetiological role of IgE-mediated inflammation of the nasal mucosa in several diseases of the upper respiratory tract, as they represent a large body of patient population seen by the general practitioner as well as the paediatrician, allergologist and otorhinolaryngologist. We here aim at reviewing the current literature on the relationship between AR and conditions in upper airways frequently encountered in everyday clinical practice, and highlight the need for further studies exploring the role of allergic inflammation in the development of these diseases. [ABSTRACT FROM AUTHOR]

Background: Low sensitization rates to common allergens have been observed in farm children, which might be due to high exposure to microbial agents. It is not known how microbial agents modify the association between specific allergen exposure and sensitization. Objective: To examine the relations between house dust mite allergen exposure and mite sensitization in farm and nonfarm children and to assess the effects of microbial agents levels on this association. Methods: Major mite allergens of Dermatophagoides pteronyssinus (Der p 1) and Dermatophagoides farinae (Der f 1), endotoxin, β(1,3)-glucans and fungal extracellular polysaccharides were measured in mattress dust of 402 children participating in a cross-sectional study in five European countries. Mite allergen (Der p 1 + Der f 1) levels were divided into tertiles with cut-offs 1.4 and 10.4 μg/g. Sensitization was assessed by measurement of allergen-specific immunoglobulin E against house dust mite. Results: Prevalence ratios of mite sensitization for medium and high when compared with low mite allergen levels were 3.1 [1.7–5.7] and 1.4 [0.7–2.8] respectively. Highest mite sensitization rates at intermediate exposure levels were consistently observed across country (except for Sweden) and in both farm and nonfarm children. The shape of the dose–response curve was similar for above and below median mattress microbial agent levels, but the ‘sensitization peak’ appeared to be lower for above median levels. Conclusions: Our data suggest a bell-shaped dose–response relationship between mite allergen exposure and sensitization to mite allergens. In populations with high microbial agent levels and low sensitization rates, the curve is shifted down. [ABSTRACT FROM AUTHOR]

Background: Correct diagnosis of immunoglobulin E (IgE)-mediated disease is the prerequisite for secondary allergy prevention during early childhood. Objective: To evaluate the diagnostic efficacy of a new blood test, Phadiatop® Infant, in detecting IgE sensitisation to food and inhalant allergens among children at 2 years of age. Methods: Children ( n = 239) were followed prospectively from birth to 2 years of age for the presence of IgE sensitisation and the development of atopic manifestations. Immunoglobulin E sensitisation was evaluated by skin prick test (SPT) and analysis of allergen-specific IgE antibodies in plasma to food and inhalant allergens. The children were classified into three groups: IgE-sensitised, non-IgE sensitised and inconclusive, depending on SPT and allergen-specific IgE results. Results: Twenty-six (11%) of the children were classified as IgE-sensitised, 182 (76%) as non-IgE sensitised and 31 (13%) as inconclusive. Phadiatop Infant was positive in 50 (21%) of the children. Ten children (4%) with identified IgE antibodies against the selected food and inhalant allergens showed negative Phadiatop Infant. Three children showed positive Phadiatop Infant but were negative in the other tests performed. These results correspond to positive and negative predictive values for Phadiatop Infant of 89 and 99%, respectively. Children with clinical symptoms of atopic diseases had significantly increased levels for Phadiatop Infant ( P < 0.01). Conclusion: Phadiatop Infant appears to be a reliable alternative to SPT and the measurement of allergen-specific IgE antibodies in plasma for detecting clinically important IgE sensitisation among children at 2 years of age. [ABSTRACT FROM AUTHOR]

Sublingual immunotherapy has been shown in some clinical studies to modulate allergen-specific antibody responses [with a decrease in the immunoglobulin E/immunoglobulin G4 (IgE/IgG4) ratio] and to reduce the recruitment and activation of proinflammatory cells in target mucosa. Whereas a central paradigm for successful immunotherapy has been to reorient the pattern of allergen-specific T-cell responses in atopic patients from a T helper (Th)2 to Th1 profile, there is currently a growing interest in eliciting regulatory T cells, capable of downregulating both Th1 and Th2 responses through the production of interleukin (IL)-10 and/or transforming growth factor (TGF)- β. We discuss herein immune mechanisms involved during allergen-specific sublingual immunotherapy (SLIT), in comparison with subcutaneous immunotherapy. During SLIT, the allergen is captured within the oral mucosa by Langerhans-like dendritic cells expressing high-affinity IgE receptors, producing IL-10 and TGF- β, and upregulating indoleamine dioxygenase (IDO), suggesting that such cells are prone to induce tolerance. The oral mucosa contains limited number of proinflammatory cells, such as mast cells, thereby explaining the well-established safety profile of SLIT. In this context, second-generation vaccines based on recombinant allergens in a native conformation formulated with adjuvants are designed to target Langerhans-like cells in the sublingual mucosa, with the aim to induce allergen-specific regulatory T cells. Importantly, such recombinant vaccines should facilitate the identification of biological markers of SLIT efficacy in humans. [ABSTRACT FROM AUTHOR]

Background: Non-specific lipid transfer proteins (LTPs) are involved in allergy to fresh and processed fruits. We have investigated the effect of thermal treatment and glycation on the physico-chemical and IgE-binding properties of the LTP from apple (Mal d 3). Methods: Mal d 3 was purified from apple peel and the effect of heating in the absence and presence of glucose investigated by CD spectroscopy, electrospray and MALDI-TOF mass spectrometry. IgE reactivity was determined by RAST and immunoblot inhibition, SPT and basophil histamine release test. Results: The identity and IgE reactivity of purified Mal d 3 was confirmed. Mild heat treatment (90°C, 20 min) in the absence or presence of glucose did not alter its IgE reactivity. More severe heat treatment (100°C, 2 h) induced minor changes in protein structure, but a significant decrease in IgE-binding (30-fold) and biological activity (100- to 1000-fold). Addition of glucose resulted in up to four glucose residues attached to Mal d 3 and only a 2- and 10-fold decrease of IgE-binding and biological activity, respectively. Conclusions: Only severe heat treatment caused a significant decrease in the allergenicity of Mal d 3 but glycation had a protective effect. The presence of sugars in fruits may contribute to the thermostability of the allergenic activity of LTP in heat-processed foods. [ABSTRACT FROM AUTHOR]