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Background: Cyclophilins are ubiquitous panallergens whose epidemiologic, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice., Objective: We investigated the epidemiologic, diagnostic, and clinical relevance of cyclophilins in seasonal allergic rhinitis and its comorbidities., Methods: We examined a random sample of 253 (25%) of 1263 Italian children with seasonal allergic rhinitis from the Panallergens in Pediatrics (PAN-PED) cohort with characterized disease phenotypes. Nested studies of sensitization prevalence, correlation, and allergen extract inhibition were performed in patients sensitized to birch pollen extract but lacking IgE to Bet v 1/2/4 (74/1263) or with highest serum level of IgE to Bet v 1 (26/1263); and in patients with sensitization to various extracts (ragweed, mugwort, pellitory, Plantago, and plane tree), but not to their respective major allergenic molecule, profilins, and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7, and extract inhibition tests were performed with the same rBet v 7., Results: IgE to rBet v 7 was detected in 43 (17%) of 253 patients. It was associated with asthma (P < .028) and oral allergy syndrome (P < .017) in univariate but not multivariate analysis adjusted for IgE to profilins (Phl p 12), PR-10s (Bet v 1), and lipid transfer proteins (Pru p 3). IgE to rBet v 7 was also highly prevalent (47/74, 63%) among patients with unexplained sensitization to birch pollen extract. In patients with unexplained sensitization to ragweed, mugwort, pellitory, Plantago and plane tree pollen, the levels of IgE to those extracts correlated with the levels of IgE to rBet v 7, and they were also significantly inhibited by rBet v 7 (inhibition range 45%-74%)., Conclusions: IgE sensitization to cyclophilin is frequent in pollen-allergic patients living in temperate areas and can produce "false" positive outcomes in skin prick and IgE tests to pollen extracts. Molecular diagnostic guidelines should include this panallergen family., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The measurement of specific IgE to allergenic extracts and molecules in patients with allergic rhinitis (AR) is crucial for a precise diagnosis and further immunotherapy. Companies providing in vitro diagnostic methods in allergology continuously strive for the optimization and modernization of such methods. A new generation of automated allergy tests based on chemiluminescence detection and paramagnetic microparticles is now available, with possible advantages in sample volume, cost-effectiveness and avoidance of sample-related interference., Objectives: To test whether sIgE antibody levels obtained with a new singleplex chemiluminescent method have a good agreement with the corresponding results obtained with a "gold standard" test., Methods: We tested sera from 368 AR patients. Specific IgE sera levels (kU/L) to a comprehensive panel of 15 allergen extracts and 6 molecules were tested with ImmunoCAP ® (Thermo Fisher Scientific Inc, Phadia AB, Uppsala, Sweden) and NOVEOS™ (HYCOR ® Biomedical, Garden Grove, CA, USA). We evaluated the qualitative and quantitative performance of the new NOVEOS system in matching the outcome of ImmunoCAP to each of the examined allergens., Results: In relation to ImmunoCAP, the overall diagnostic sensitivity and specificity of sIgE tests with NOVEOS were 90.8% (95% CI = 88.6-92.7) and 96.2% (95% CI = 93.9-97.8), respectively. These values were higher when only molecules were considered (sensitivity = 98.7% [95% CI = 96.4%-99.7%]; specificity = 94.2% [95% CI = 88.4%-97.6%]) and lower when only extracts were considered (sensitivity = 87.6% [95% CI = 84.7%-90.2%]; specificity = 97% [95% CI = 94.4%-98.6%]). Spearman's correlation between the data set of both methods for a ≥ 0.1 kU/L cut-off was 0.84 (p < .001)., Conclusions: The new singleplex NOVEOS system presented good results for qualitative and quantitative comparisons when testing specific serum IgE antibodies against a range of 21 allergens. This novel immunoassay system using only 4 µl of sample per test appears to be robust and reliable and can, therefore, be used as an aid in allergy diagnosis., (© 2020 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Background: Atopic dermatitis (AD) represents a chronic skin disorder seriously affecting patients' QoL and is often associated with immunological imbalance, disorders of the skin barrier function and environmental factors., Objective: We extensively studied the proteomic IgE sensitization profile in a large AD Mediterranean cohort., Methods: A total of 588 individuals with moderate-severe (70.6%) or mild and/or history of (29.4%) AD were evaluated in comparison to 1285 unselected atopic controls (AC) with a history of adverse reactions to foods, allergic rhinitis and/or bronchial asthma by means of ImmunoCAP ISAC 112 ® and Allergy Explorer-ALEX® microarray analysis., Results: The olive tree pollen β-1,3-glucanase rOle e 9 and the manganese superoxide dismutase from Aspergillus rAsp f 6 were the molecules most significantly associated with AD occurrence and allowed to discriminate among the moderate and severe forms of disease. An IgE hyper-reactivity to cypress, grasses, olive tree, house dust mites (including rDer p 11), and to all cross-reactive components except profilin and polcalcin was observed. About 60% of adults with severe AD were sensitized to nsLTPs. Cross-reactive carbohydrate determinants (CCDs) IgE was found in about one-third of AD participants. Hen eggs nGal d 1 IgE sensitization was more prevalent in the paediatric population, whilst rAsp f 6 and rOle e 9 reactivity was found particularly in older patients. Despite the status of widespread IgE sensitization to both environmental and food allergens, a reduced frequency of patient-reported severe reactions to food or of asthma was observed in AD patients compared to AC, particularly in case of concomitant Ole e 9 reactivity., Conclusion and Clinical Relevance: Testing IgE reactivity to a large panel of molecular components unveils important associations between IgE reactivity profiles and AD clinical presentation, highlights the allergens useful for a precise AD signature and allows the detection of interesting sensitisations patterns., (© 2019 John Wiley & Sons Ltd.)

Background: The order Fagales represents an important cause of tree-pollen allergy in northern countries. We investigated the IgE recognition profiles, mutual relationships, and association with clinical symptoms of a panel of allergens belonging to the PR-10 family, the main proteins responsible for Fagales allergy (Act d 8, Aln g 1, Api g 1, Ara h 8, Bet v 1, Cor a 1.0101, Cor a 1.0401, Gly m 4, Mal d 1, and Pru p 1)., Methods: A total of 526 PR-10-reactive subjects living in central and southern Italy were studied by ImmunoCAP-ISAC-112 microarray analysis., Results: Overall, Bet v 1 reactivity was the most commonly (74%) observed among PR-10 proteins, but Cor a 1.0101 was the most prevalent in participants aged <6 years, and between 15 and 65 years. Overall, 26% of the PR-10-reactive persons were Bet v 1 negative, whilst 93.6% of the PR-10 polyreactive individuals were Bet v 1 positive. Among the 10 PR-10s evaluated, 100 combinations were recorded. The strongest association was observed between molecules with the highest sequence identities (Bet v 1 and Cor a 1.0101, Cor a 1.0401 or Aln g 1; Mal d 1 and Pru p 1). Bet v 1-, Cor a 1.0101-, and Aln g 1-specific IgE recognition was associated with respiratory symptoms, whilst Ara h 8, Cor a 1.0401, Gly m 4, Mal d 1, and Pru p 1 were selectively linked to an oral allergic syndrome., Conclusions: Testing IgE reactivity to a panel of PR-10s in a birch-free area discloses peculiar relationships between clinical phenotypes and sensitization profiles, allowing the identification of novel cluster patterns., (© 2017 S. Karger AG, Basel.)

Background: Sézary syndrome (SS) is the aggressive leukemic form of cutaneous T cell lymphoma characterized by erythroderma, the presence of a malignant circulating T memory cells with skin homing potential, and the ability to produce a variety of Th2 soluble factors, such as IL-4 and IL-5. We measured total and specific IgE in SS patients as a further parameter of a Th2-skewed immune system, and studied their clinical impact., Methods: Specific IgE production in a cohort of 55 SS patients was evaluated by the molecule-based ISAC microarray system. We then evaluated survival times and the hazard ratios in this cohort by Kaplan-Meier and Cox methods., Results: Twenty-four (43.6%) SS patients had specific IgE to both environmental and food allergens. For survival analysis, patients found positive to at least one allergen were defined as IgE+. By comparing IgE+ versus IgE- we found a significant difference in the median survival times, 2.9 versus 8.9 years (p < 0.001). Conversely, no survival difference could be observed when total IgE levels were considered. IgE+ patients had higher levels of CD60+CD49-CD4+ T cells, which also represent another worse prognostic index recently identified., Conclusion: SS patients had specific IgE to both environmental and food allergens. IgE+ SS patients had a significant lower survival rate. High levels of CD60-CD49+CD4+ T cells associated with an IgE- phenotype allow the identification of a restricted group of long survivor SS patients. Therefore, specific measurement of IgE seems to be useful in discriminating survival., (Copyright © 2011 S. Karger AG, Basel.)

Background: Allergies represent the most prevalent non infective diseases worldwide. Approaching IgE-mediated sensitizations improved much by adopting allergenic molecules instead of extracts, and by using the micro-technology for multiplex testing., Objective and Methods: To provide a proof-of-concept that a flow cytometric bead array is a feasible mean for the detection of specific IgE reactivity to allergenic molecules in a multiplex-like way. A flow cytometry Allergenic Molecule-based micro-bead Array system (ABA) was set by coupling allergenic molecules with commercially available micro-beads. Allergen specific polyclonal and monoclonal antibodies, as well as samples from 167 allergic patients, characterized by means of the ISAC microarray system, were used as means to show the feasibility of the ABA. Three hundred and thirty-six sera were tested for 1 or more of the 16 selected allergens, for a total number of 1,519 tests on each of the two systems., Results: Successful coupling was initially verified by detecting the binding of rabbit polyclonal IgG, mouse monoclonal, and pooled human IgE toward three allergens, namely nDer s 1, nPen m 1, and nPru p 3. The ABA assay showed to detect IgE to nAct d 1, nAct d 11, rAln g 1, nAmb a 1, nArt v 3, rBet v 1, rCor a 1, nCup a 1, nDer p 1, nDer s 1, rHev b 5, nOle e 1, rPar j 2, nPen m 1, rPhl p 1, and nPru p 3. Results obtained by ABA IgE testing were highly correlated to ISAC testing (r = 0.87, p<0.0001). No unspecific binding was recorded because of high total IgE values., Conclusion: The ABA assay represents a useful and flexible method for multiplex IgE detection using allergenic molecules. As also shown by our initial experiments with monoclonals and polyclonals, ABA is suitable for detecting other human and non-human immunoglobulins.

Purpose of Review: To define the role of IgE-microarray testing in atopic dermatitis where the multifunctional environmental factors implicated in the pathogenesis of the disease deserve a complex and exhaustive approach for the finest definition of relevant allergenic triggers, if any., Recent Findings: Allergenic factors involved in atopic dermatitis have been reported in inducing atopic dermatitis. Environmental triggers, such as aeroallergens, food allergens, bacterial, and fungal antigen, and the presence of IgE to self-antigens have been described as well. The usefulness of the microarray testing has been preliminary described., Summary: As far as the number of potential triggers or worsening factors in atopic dermatitis is quite broad, we foresee a crucial role for the IgE microarray testing. The microarray testing is helpful in defining all additional reactivity the atopic dermatitis patient could have acquired in her/his allergic life, mostly related to inhalant allergens. Nevertheless, interpretation needs skills and thus this new technology should rather be reserved for the allergologist as it may lead to false conclusions if broadly used in general medicine. IgE microarray testing gives trustable results to define the nonallergic atopic dermatitis form because of the broad and comprehensive negative IgE testing.

Background: IgE recognition of panallergens having highly conserved sequence regions, structure, and function and shared by inhalant and food allergen sources is often observed., Methods: We evaluated the IgE recognition profile of profilins (Bet v 2, Cyn d 12, Hel a 2, Hev b 8, Mer a 1, Ole e 2, Par j 3, Phl p 12, Pho d 2), PR-10 proteins (Aln g 1, Api g 1, Bet v 1.0101, Bet v 1.0401, Cor a 1, Dau c 1 and Mal d 1.0108) and tropomyosins (Ani s 3, Der p 10, Hel as 1, Pen i 1, Pen m 1, Per a 7) using the Immuno-Solid phase Allergen Chip (ISAC) microarray system. The three panallergen groups were well represented among the allergenic molecules immobilized on the ISAC. Moreover, they are distributed in several taxonomical allergenic sources, either close or distant, and have a route of exposure being either inhalation or ingestion., Results: 3,113 individuals (49.9% female) were selected on the basis of their reactivity to profilins, PR-10 or tropomyosins. 1,521 (48.8%) patients were reactive to profilins (77.6% Mer a 1 IgE(+)), 1,420 (45.6%) to PR-10 (92.5% Bet v 1 IgE(+)) and 632 (20.3%) to tropomyosins (68% Der p 10 IgE(+)). A significant direct relationship between different representative molecules within each group of panallergens was found. 2,688 patients (86.4%) recognized only one out of the three distinct groups of molecules as confirmed also by hierarchical clustering analysis., Conclusions: Unless exposed to most of the allergens in the same or related allergenic sources, a preferential IgE response to distinct panallergens has been recorded. Allergen microarray IgE testing increases our knowledge of the IgE immune response and related epidemiological features within and between homologous molecules better describing the patients' immunological phenotypes.

IgE-mediated allergic diseases are among the most prevalent diseases worldwide. The use of extracts in the skin test and the additional use of IgE testing still represent the current basis for the diagnostic work-up. During the past 30 years, knowledge of the molecular structure of allergens has increased dramatically, and the characterization and production of allergenic molecules, as natural purified compounds or recombinant products, is allowing us to approach the allergy diagnostic work-up differently. Much of this is based on the adoption of microtechnology since the first release of a biochip for IgE detection. Its use has prompted the development of new concepts linked to the diagnosis of allergic diseases. This review describes the background of allergy diagnosis and the tools currently used for specific IgE detection. It gives insight into the most recent advancement in the field of biotechnology leading to allergenic molecule availability, microtechnology leading to the routine use of protein biochips for IgE detection, and how they should be combined with information technology.

Kiwellin, an allergenic protein formerly isolated from green kiwi fruit, has been identified as the most abundant component of the gold kiwi species. A protein named KiTH, showing a 20 kDa band on reducing SDS-PAGE and 100% identity with the C-terminal region of kiwellin, has been identified in the extract of the ripe green species. In vitro treatment of purified kiwellin with the protease actinidin from green kiwi fruit originated KiTH and kissper, a recently described pore-forming peptide. Primary structure analysis and experimental evidence suggest that kiwellin is a modular protein with two domains. It may undergo in vivo proteolytic processing by actinidin, thus producing KiTH and kissper. When probed with sera recognizing kiwellin from green kiwi fruit, KiTH showed IgE binding, with reactivity levels sometimes different from those of kiwellin. The IgE-binding capacity of kiwellin from gold kiwi fruit appears to be similar to that of the green species.

(1) Background: Atopic dermatitis constitutes one of the most common inflammatory skin manifestations of the pediatric population. The onset of many inborn errors occurs early in life with an AD–like picture associated with a deregulated IgE response. The availability of proteomic tests for the simultaneous evaluation of hundreds of molecules allows for more precise diagnosis in these cases. (2) Methods: Comparative genomic hybridization microarray (Array–CGH) analysis and specific IgE evaluation by using allergenic microarray (ISAC) and microarray (ALEX2) systems were performed. (3) Results: Proteomic investigations that use multiplex methods have proven to be extremely useful to diagnose the sensitization profile in inborn errors with deregulated IgE synthesis. Four patients with rare diseases, such as recessive X–linked ichthyosis (RXLI, OMIM 308100), Comel–Netherton syndrome (NS, OMIM256500), monosomy 1p36 syndrome (OMIM: 607872), and a microduplication of Xp11.4 associated with extremely high levels of IgE: 7.710 kU/L, 5.300 kU/L, 1.826 kU/L, and 10.430 kU/L, respectively, were evaluated by micro– and macroarray multiplex methods. Polyreactivity to both environmental and food allergens was observed in all cases, including the first described case of association of X–chromosome microduplication and HIE. (4) Conclusions: Extensive use of proteomic diagnostics should be included among the procedures to be implemented in inborn errors with hyper–IgE. [ABSTRACT FROM AUTHOR]

Background: Scant data are currently available on the allergen-specific immunoglobulin (Ig)E sensitization profile in primary immunodeficiencies with hyper IgE. Netherton syndrome (NS, OMIM 266500) is an extremely rare form of congenital ichthyosis characterized by congenital scaly erythroderma, hair abnormalities, and deregulated IgE reactivity associated with severe atopic manifestations. Objective: The aim of this study was to evaluate the feasibility and reliability of a multiplex proteomic approach in the detection of specific IgE in NS. Methods: Specific IgE was evaluated in 10 individuals with an established molecular diagnosis of NS using an allergenic molecules microarray (immuno-solid-phase allergen chip). Results: Polireactivity to airway allergens, mainly house dust mites and olive tree pollen, and food allergens were observed in NS. Eighty per cent of patients were responsive to LTP or profilins. A clinical history suggestive of severe egg, milk, and fish allergy was confirmed by reactivity to the thermostable molecules Gal d 1, Bod 8, and parvalbumin Gad c 1, respectively. Latex reactivity was associated with Hev b 5 and 6 reactivity. Two distinct clusters of reactivity were observed after hierarchical analysis. Extremely high IgE levels (> 10,000 kU/L) do not affect the results obtained with microarrays. Conclusion: IgE multiplex evaluation allows (i) to profile IgE polyreactivity pictures, in the presence of LTP and profilin sensitization, (ii) to verify the clinical history of food allergy to milk, egg, and seafood, (iii) to confirm the allergic events associated with latex exposure, and (iv) to disclose the presence of preclinical sensitizations in patients affected by primary immunodeficiencies with hyper IgE, such as the NS. [ABSTRACT FROM AUTHOR]

• Diagnosis of fish may represent an important challenge for the allergists. • There is not a complete cross reactivity among different ß-parvalbumins. • Comprehensive panel of fish allergens is useful for the diagnosis of allergy. Diagnosis of fish may represent an important challenge for the allergists. This study aimed to evaluate the diagnostic sensitivity of an in vitro multiplex assay using a comprehensive panel of fish allergens and the cross-reactivity patterns between different molecular components. 56 subjects with fish allergy were enrolled. All patients underwent specific IgE measurement using the Allergy Explorer-Alex 2™ multiplex assay (Macroarray Diagnostics, Vienna, Austria) The single ß-parvalbumins Clu h 1, Cyp c 1, Gad m 1, Sal s 1, Sco s 1, Thu a 1 and Xyp g 1 scored positive in 75.0%, 67.8%, 62.5%, 80.3%,80.3%, 78.8% and 73,2% patients, respectively. 14.3% scored positive for the α-parvalbumin (Raj c-parvalbumin), and 16.1% for the aldolase + enolase (Gad m 2 + 3) components. 92.8% reacted to at least one ß-parvalbumin and 96.4% to at least one of the allergens tested. Overall sensitivity was higher than that obtained using commercial extracts of cod, salmon and tuna for skin prick test (75.8%) and IgE detection (92.3%). The Alex 2 showed high diagnostic sensitivity and it might be used as an additional assay to investigate the cross-reactivity patterns between different molecular components, looking for potentially safe fish species. [ABSTRACT FROM AUTHOR]

Background: Clinically complex phenotypes require more and more sophisticated and comprehensive diagnostic approaches, able to discriminate genuine sensitizations from cross‐reactivity. Interpretative complexity of multiplex diagnostic arrays has somewhat limited their diffusion. This study compares two currently available methods, namely ISAC® test and ALEX2® test. Methods: In total, 140 allergic individuals, with a history of atopic dermatitis, adverse food reactions, allergic rhinitis and/or bronchial asthma were studied by Allergy Explorer‐ALEX2® macroarray and ImmunoCAP ISAC112®. Lin's concordance correlation coefficient, intraclass correlation coefficient and Bland–Altman plots were used to verify the agreement between continuous values. Cohen's kappa coefficient (k) was assessed for the molecules available in both tests. The degree of relationship was analysed using Spearman's correlation (quantitative variables) and Pearson's χ2 or Fisher's exact test (categorical variables). Results: A substantial agreement (κ = 0.795) was observed between the two methods with 94,3% concordant results when results were dichotomized as negative or positive, but if double‐negative results were discarded, the agreement dropped to 71%. Conversely, little or no concordance was observed comparing raw data. Considering the 102 molecules shared by both systems, 28/102 (27%) showed an almost perfect agreement (k > 0.81), and concordance was good (k > 0.61) in a further 32 (31%) cases. A perfect to substantial agreement was observed by comparing species‐specific aeroallergens. Heterogeneous results emerged comparing panallergens (co‐recognition ranging from 30% for tropomyosin/serum albumins to 70% for PR‐10/profilin). The correlation among LTP, profilin and PR‐10 assayed with ISAC® was better than ALEX2®, but the latter identified more positive cases due to the wider number of molecules available. The CCD blocker provided by ALEX® test abolishes the carbohydrate determinants signal in 60% of the 33 cases reactive to MUXF3 on the ISAC® test. Conclusion: Despite the excellent concordance of the species‐specific markers, the analysis of the panallergens provided in both methods suggests a better performance of the ISAC® test on those components, while the ALEX2® test, which includes a larger number of allergens, allowing a broader molecular detection. [ABSTRACT FROM AUTHOR]

Background: Discovered and described 40 years ago, non‐specific lipid transfer proteins (nsLTP) are present in many plant species and play an important role protecting plants from stressors such as heat or drought. In the last 20 years, sensitization to nsLTP and consequent reactions to plant foods has become an increasing concern. Aim: The aim of this paper is to review the evidence for the structure and function of nsLTP allergens, and cross‐reactivity, sensitization, and epidemiology of nsLTP allergy. Materials and Methods: A Task Force, supported by the European Academy of Allergy & Clinical Immunology (EAACI), reviewed current evidence and provide a signpost for future research. The search terms for this paper were "Non‐specific Lipid Transfer Proteins", "LTP syndrome", "Pru p 3", "plant food allergy", "pollen‐food syndrome". Results: Most nsLTP allergens have a highly conserved structure stabilised by 4‐disulphide bridges. Studies on the peach nsLTP, Pru p 3, demonstrate that nsLTPs are very cross‐reactive, with the four major IgE epitopes of Pru p 3 being shared by nsLTP from other botanically related fruits. These nsLTP allergens are to varying degrees resistant to heat and digestion, and sensitization may occur through the oral, inhaled or cutaneous routes. In some populations, Pru p 3 is the primary and sole sensitizing allergen, but many are poly‐sensitised both to botanically un‐related nsLTP in foods, and non‐food sources of nsLTP such as Cannabis sativa, Platanus acerifolia, (plane tree), Ambrosia artemisiifolia (ragweed) and Artemisia vulgaris (mugwort). Initially, nsLTP sensitization appeared to be limited to Mediterranean countries, however more recent studies suggest clinically relevant sensitization occurs in North Atlantic regions and also countries in Northern Europe, with nsLTP sensitisation profiles being broadly similar. Discussion: These robust allergens have the potential to sensitize and provoke symptoms to a large number of plant foods, including those which are raw, cooked or processed. It is unknown why some sensitized individuals develop clinical symptoms to foods whereas others do not, or indeed what other allergens besides Pru p 3 may be primary sensitising allergens. It is clear that these allergens are also relevant in non‐Mediterranean populations and there needs to be more recognition of this. Conclusion: Non‐specific LTP allergens, present in a wide variety of plant foods and pollens, are structurally robust and so may be present in both raw and cooked foods. More studies are needed to understand routes of sensitization and the world‐wide prevalence of clinical symptoms associated with sensitization to these complex allergens. [ABSTRACT FROM AUTHOR]

Mosquito bite is usually followed by a local reaction, but severe or systemic reaction may, in rare cases, occur. Allergic reactions to Aedes communis (Ac) may be underestimated due to the lack of reliable diagnostic tools. In this multicenter study, 205 individuals reporting large local reactions to Ac were enrolled and studied for cutaneous or IgE reactivity to Ac, Blattella germanica, Penaeus monodon, and Dermatophagoides pteronyssinus. Extract and molecular IgE reactivity to bees, wasps, hornets, and yellow jacket venoms were also studied in 119 patients with a clinical history of adverse reaction to Hymenoptera. Immunoblot (IB) analysis and immunoCAP IgE inhibition experiments were carried out in selected sera. Ac sensitization was recorded in 96 (46.8%) patients on SPT. Strict relationship between Ac and D. pteronyssinus, B. germanica, P. monodon, or Apis mellifera reactivity on SPT was observed. Ac IgE recognition was seen in 60/131 (45.8%) patients, 49 (81.6%) of them SPT positive, and 5/14 IB reactors. Ac IgE sensitization was associated with Tabanus spp, A. mellifera, Vespula vulgaris, and Polistes dominula reactivity. A strict relationship between Ac IgE reactivity and Api m 1, Api m 2, Api m 3, Api m 5, and Api m 10 was recorded. IgE reactivity to AC was inhibited in 9/15 cases after serum absorption with the A. mellifera extract. Both SPT and IgE Ac reactivity is observed in about half of patients with a history of large local reactions to mosquito bites. The significant relationship between Ac sensitization and either extract or single bee venom components is suggestive of a “bee-mosquito syndrome” occurrence. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, which generally presents with intense itching and recurrent eczematous lesions. AD affects up to 20% of children and 10% of adults in high-income countries. The prevalence and incidence of AD have increased in recent years. The onset of AD mostly occurs in childhood, although in some cases AD may persist in adult life or even manifest in middle age (adult-onset AD). AD pathophysiology is made of a complex net, in which genetic background, skin barrier dysfunction, innate and adaptive immune responses, as well as itch contribute to disease development, progression, and chronicization. One of the most important features of AD is skin dehydration, which is mainly caused by filaggrin mutations that determine trans-epidermal water loss, pH alterations, and antigen penetration. In accordance with the "outside-inside" theory of AD pathogenesis, in a context of an altered epidermal barrier, antigens encounter epidermal antigen presentation cells (APCs), such as epidermal Langerhans cells and inflammatory epidermal dendritic cells, leading to their maturation and Th-2 cell-mediated inflammation. APCs also bear trimeric high-affinity receptors for immunoglobulin E (IgE), which induce IgE-mediated sensitizations as part of pathogenic mechanisms leading to AD. In this review, we discuss the role of cytokines in the pathogenesis of AD, considering patients with various clinical AD phenotypes. Moreover, we describe the cytokine patterns in patients with AD at different phases of the disease evolution, as well as in relation to different phenotypes/endotypes, including age, race, and intrinsic/extrinsic subtypes. We also discuss the outcomes of current biologics for AD, which corroborate the presence of multiple cytokine axes involved in the background of AD. A deep insight into the correlation between cytokine patterns and the related clinical forms of AD is a crucial step towards increasingly personalized, and therefore more efficient therapy. [ABSTRACT FROM AUTHOR]

Background: Immunoglobluin E (IgE)-mediated hypersensitivity to natural rubber latex (NRL) is a major problem in allergy practice. Currently, the use of skin prick tests (SPTs) with latex extracts and specific IgE detection for the diagnosis of NRL allergy in suspected patients is directed to identification of risk factors. Many cases of NRL allergy remain undiagnosed due to misreporting of symptoms by the patients or lack of proper questions asked by the physician. Materials and Methods: A total of 6,126 subjects referred for respiratory symptoms underwent SPTs with NRL. Positive subjects were resurveyed for exposure to NRL, and specific IgE for NRL extracts and recombinant molecules was determined. Immunoblots of NRL extracts were performed to identify IgE patterns. Results: Forty-six of 3,930 sensitized subjects had a positive SPT with NRL, displaying a prevalence of NRL sensitization of 0.75% for the general and 1.2% for the sensitized population. Eleven out of 46 (23.9%) subjects could be defined as NRL asymptomatic, whereas 35 (76.1%) developed symptoms upon exposure to NRL. Specific IgE to NRL was detected for 22 (75.86%) of 29 tested sera. Seventeen out of 22 (77%) sera displayed specific IgE to recombinant allergens with most reactions to Hev b 5, Hev b 6.01 and Hev b 6.02. Immunoblots of NRL extract fractions with patients’ sera showed heterogeneous patterns. Conclusions: SPTs with NRL extract should be routinely performed in patients with respiratory symptoms. Hev b 5, Hev b 6.01 and Hev b 6.02 are the most important allergens, but further characterization of NRL extracts is needed to identify novel allergens and to clarify the role of crossreactive carbohydrate determinants. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article discusses the role of common environmental allergens in atopic dermatitis. Widely quoted effects of in vitro formed IgE complexes with heterologous anti-IgE include the release of arachidonic acid from mouse macrophages, inhibition of human neutrophil chemotaxis and activation of human suppressor T cells for IgE synthesis by a myelomatous cell line. All these observations may relate to effects of IgE complexes formed in vivo, and particularly to those containing autoanti-IgE. A link between IgE complexes made of IgE and other isotypes, induction of cell mediated reactions can therefore be traced, and the novel findings linking mast cells to neuroendocrine influences might open new insight into the role of immune complexes in atopic dermatitis.