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House dust mites (HDM) represent a major source of allergens, contributing to the increasing incidence of type I hypersensitivity disease worldwide. Over 30 different IgE-binding proteins from the HDM extract were detected. Although group 1 and 2 have been identified as major allergens, due to the safety and efficacy of allergy diagnosis and immunotherapy, there is a need to carefully evaluate the clinical relevance of other allergens present in the HDM extract. In regard to this, a high molecular mass allergen of about 68 kD was purified from the HDM extract using a combination of gel permeation chromatography and reversed-phase chromatography. The IgG and IgE reactivity of the purified protein were preserved during the purification process, as confirmed by Western blot analysis with polyclonal rabbit antibodies and dot blot analysis with a pool of sera from subjects with house dust mite allergy, respectively. In addition, the IgE reactivity was confirmed using ELISA testing with nine patient sera. The biological potency of the 68 kD allergen was confirmed by skin prick testing in five allergic subjects, suggesting that the high molecular mass allergen is a good candidate for component-resolved diagnosis of house dust mite allergy and eventual therapeutic treatment. Grinje iz kućne prašine predstavljaju jedan od glavnih izvora alergena koji su u značajnoj meri doprineli porastu prvog tipa preosetljivosti. Preko 30 IgE-vezujućih proteina iz kućne prašine je detektovano do danas. Alergeni grupe 1 i 2 označeni su kao glavni alergeni kućne prašine. Međutim, da bi se poboljšala sigurnost i efikasnost dijagnoze i terapije alergijskih oboljenja izazvanih grinjama iz kućne prašine, neophodno je odrediti klinički značaj svih alergena iz ovog alergenskog izvora. U ovom radu izolovan je alergen visoke molekulske mase od 68 kD iz ekstrakta kućne prašine kombinovanjem gel-permeacione hromatografije i reversno-fazne hromatografije. IgG i IgE reaktivnost prečišćenog proteina je proverena u 'Western blot'-u i 'dot blot'-u sa poliklonskim zečijim antitelima na ekstrakt kućne prašine i 'pool'-om seruma osoba alergičnih na kućnu prašinu, redom. 64 % pacijenata je pokazalo IgE reaktivnost na prečišćeni protein u ELISA testu. Biološka reaktivnost prečišćenog alergena je potvrđena u kožnim probama na pet pacijenata, ukazujući da je prečišćen alergen dobar kandidat za dijagnozu alergije na kućnu prašinu pojedinačnim komponentama i eventualni terapeutski tretman.

Herbex-kid (HK), a polyherbal formulation was evaluated in various experimental allergic models of Type I hypersensitivity reactions. Compound 48/80 (C 48/80) has been shown to induce rat mesentery mast cell degranulation and HK (1.07, 10.75 and 107.5 mg ml−1) inhibited the mast cell degranulation in a dose dependent manner. HK (1.07, 10.75 and 107.5 mg kg−1; p.o.) showed dose-dependent protection against C 48/80 induced systemic anaphylaxis in male Balb/C mice. In active anaphylaxis model, male Wistar rats orally administered with 10.75 and 107.5 mg kg−1of HK showed significant (P −1showed significant (P −1it showed significant (P P

Objective: To investigate the peritoneal mast cell stabilization activity of Ziziphus xylopyrus extracts. Materials and Methods: Ziziphus Xylopyrus L. (family- Rhamnaceae) stem part was successively extracted with ethanol and aqueous to prepare extract of the plant. The extracts of Ziziphus Xylopyrus (Z. xylopyrus) were evaluated for stabilization of mast cell in rat for the evaluation of Hypersensitivity type I allergic reaction in animal models. The extract of Z. xylopyrus ethanolic and aqueous (1, 10 and 100 μg/ml) was evaluated for peritoneal mast cell stabilization activity in rat mesenteric preparation induced by C 48/80. Result: Preliminary phytochemical analysis revealed the presence of carbohydrates, fixed oil, proteins, alkaloids, glycosides, flavonoids and phenolic compounds. The ethanolic and aqueous extracts of Z. xylopyrus showed dose dependent increase in the number of intact cells when compare with C 48/80 at the concentration of 10 and 100 μg/ml. It virtues further work towards the isolation of phyto constituents from this plant. Conclusion: This finding provides evidence that the Z. xylopyrus inhibits mast cell-derived immediate-type allergic reactions and mast cell degranulation. Z. xylopyrus has a potential as allergic anti-asthmatic agent.

Allergic fungal rhinosinusitis (AFRS) is the most common form of fungal sinusitis in the United States. Its pathophysiological basis is associated with a predisposed person's type I IgE-mediated allergic response to inhaled mold spores that are ubiquitous in the environment. AFRS is a well-recognized type of chronic, recurrent, and non-invasive hypertrophic sinus disease that affects immunocompetent hosts, most commonly young African American males. There are 5 main criteria used for the diagnosis of AFRS, one being the presence of nasal polyposis. A review of the current literature was performed in order to provide the most up-to-date knowledge regarding the background, diagnosis, management, recent research, and controversies surrounding AFRS. Although much is known about the pathophysiology and etiology of this disease, controversy exists regarding the importance of type I hypersensitivity in AFRS, as humoral immunity and immunoglobulin-independent pathways may also contribute. The potential role of local sinonasal IgE production in the pathophysiology of AFRS is an area of discussion, as is the role of preoperative antifungal medication in improving postoperative patient outcomes. Recent advancements in the diagnosis of AFRS include identification of genes and proteins unique to or over-expressed in AFRS patients. Although AFRS is a well-known and well-described cause of nasal polyposis, controversy still exists regarding this diagnosis. Advances in research may eventually resolve any diagnostic controversies in AFRS.

Immunoglobulin E (IgE) is implicated in immunity against parasitic infections. However, its prominent role in type I hypersensitivity and anaphylactic reactions has attracted attention for therapeutic interventions. Disorders such as allergic rhinitis (hay fever), asthma, atopic dermatitis (eczema), and food allergies are an increasing problem in need of effective therapies. Central to each of these disorders is the interplay between IgE and its receptors, FceRI and FceRII, on mast cells and other inflammatory cell types. Given its potential to generate acute immunological reactions, the level and activity of IgE is tightly regulated on several tiers: de novo production, uptake by, and regulation of its receptors on a wide range of cell types. In this article, we discuss the biology of IgE and its role in the pathophysiology of allergic diseases.

Mast cells play a central role in type I hypersensitivity reactions and allergic disorders such as anaphylaxis and asthma. Activation of mast cells, through a cascade of phosphorylation events, leads to the release of mediators of the early phase allergic response. Understanding the molecular architecture underlying mast cell signaling may provide possibilities for therapeutic intervention in asthma and other allergic diseases. Although many details of mast cell signaling have been described previously, a systematic, quantitative analysis of the global tyrosine phosphorylation events that are triggered by activation of the mast cell receptor is lacking. In many cases, the involvement of particular proteins in mast cell signaling has been established generally, but the precise molecular mechanism of the interaction between known signaling proteins often mediated through phosphorylation is still obscure. Using recently advanced methodologies in mass spectrometry, including automation of phosphopeptide enrichments and detection, we have now substantially characterized, with temporal resolution as short as 10 s, the sites and levels of tyrosine phosphorylation across 10 min of FcεRI-induced mast cell activation. These results reveal a far more extensive array of tyrosine phosphorylation events than previously known, including novel phosphorylation sites on canonical mast cell signaling molecules, as well as unexpected pathway components downstream of FcεRI activation. Furthermore, our results, for the first time in mast cells, reveal the sequence of phosphorylation events for 171 modification sites across 121 proteins in the MCP5 mouse mast cell line and 179 modification sites on 117 proteins in mouse bone marrow-derived mast cells.

Given the importance of immunoglobulin (Ig) E in mediating type I hypersensitivity, inhibiting IgE production would be a general way of controlling allergic disease. The low-affinity IgE receptor (FceRII or CD23) has long been proposed to be a natural regulator of IgE synthesis. In vivo research supporting this concept includes the observation that mice lacking CD23 have increased IgE production whereas mice overexpressing CD23 show strongly suppressed IgE responses. In addition, the finding that mice injected with monoclonal antibody directed against the coiled-coil stalk of CD23 have enhanced soluble CD23 release and increased IgE production demonstrates that full-length, trimeric CD23 is responsible for initiating an IgE inhibitory signal. The recent identification of ADAM10 (a disintegrin and metalloprotease) as the CD23 metalloprotease provides an alternative approach for designing therapies to combat allergic disease. Current data suggest that stabilizing cell-surface CD23 would be a natural means to decrease IgE synthesis and thus control type I hypersensitivity.

Glatiramer acetate (GA), a well tolerated immunomodulatory treatment for relapsing—remitting multiple sclerosis (RR-MS), consists of a 4-amino acid polymer that mimics the myelin basic protein (MBP). We report the first case of biopsy-proven erythema nodosum (EN) in a patient presenting RR-MS under GA treatment. Comprehensive exams were negative in the search of the etiology of EN, which spontaneously resolved despite treatment continuation. GA treatment is known to generate reactive polyclonal antibodies that can cross-react with myelin epitopes, like MBP. These antibodies may also be implicated in allergenic reactions and auto-immune adverse events, such as anaphylactic shock, lymphadenopathy, livedo-like dermatitis, or lymphocytic infiltration. EN is an unspecific skin reaction occurring in several disorders and induced by many treatments. As EN can result from a polyclonal antibody response or type I hypersensitivity mechanisms, we hypothesize that GA treatment could be responsible for the occurrence of EN. Multiple Sclerosis 2007; 13: 941—944. http://msj.sagepub.com

A broad spectrum of adverse events is reported following human vaccination but such reactions are considered to be relatively rare. A variety of mechanisms has been proposed to account for such adverse events. These most commonly relate to the actual process of vaccination and range from the vagal reaction associated with anxiety about needle injection, to use of an inappropriate site of administration, or infection of the healthcare worker by accidental injection during needle-capping. Other adverse events directly associated with the vaccine include reversion to virulence of attenuated vaccine strains of organisms, or contamination of the vaccine product. Adverse events may involve immune-mediated phenomena triggered by exposure to the microbial or other components of vaccines. These include: classical IgE-mediated type I hypersensitivity reactions, and immune-complex type III hypersensitivity (Arthus) reactions. Such reactions may be localized or systemic in nature. A variety of autoimmune reactions has been suggested to be triggered by vaccination, but in general the evidence for such associations remains largely anecdotal. Finally, many reported adverse events are simply chance instances of infection or disease onset around the time of vaccination and are not causally associated with administration of vaccine.

Fullerenes are a class of novel carbon allotropes that may have practical applications in biotechnology and medicine. Human mast cells (MC) and peripheral blood basophils are critical cells involved in the initiation and propagation of several inflammatory conditions, mainly type I hypersensitivity. We report an unanticipated role of fullerenes as a negative regulator of allergic mediator release that suppresses Ag-driven type I hypersensitivity. Human MC and peripheral blood basophils exhibited a significant inhibition of IgE dependent mediator release when preincubated with C60 fullerenes. Protein microarray demonstrated that inhibition of mediator release involves profound reductions in the activation of signaling molecules involved in mediator release and oxidative stress. Follow-up studies demonstrated that the tyrosine phosphorylation of Syk was dramatically inhibited in Ag-challenged cells first incubated with fullerenes. In addition, fullerene preincubation significantly inhibited IgE-induced elevation in cytoplasmic reactive oxygen species levels. Furthermore, fullerenes prevented the in vivo release of histamine and drop in core body temperature in vivo using a MC-dependent model of anaphylaxis. These findings identify a new biological function for fullerenes and may represent a novel way to control MC-dependent diseases including asthma, inflammatory arthritis, heart disease, and multiple sclerosis.

Reports suggest that pyrethrum, the insecticidally active extract from Chrysanthemum cinerariifolium, can induce Type I hypersensitivity reactions in humans. Using knowledge of pyrethrum chemistry and an evidence-based analysis of literature, whether current refined pyrethrum induces and/or elicits skin manifestations of contact urticaria was assessed. Current extraction and refinement techniques suggest that refined pyrethrum lacks the presence of significant, if any, proteins speculated to induce Type I hypersensitivity. Our interpretation suggests that no reports of Type I reactions presented in the literature fulfill the criteria for immunologic contact urticaria. Future patient testing with current commercial material should clarify its Type I immunologic potential, if any.

Cockroach (CR) allergies caused by the American cockroach hyave been recognized to be repsonsible for IgE-mediated type I hypersensitivity worldwide. Per a 10 is one of the recognized main allergens of the American CR. In a previous study, we examined another American CR allergen, Per a 9 in patients with CR allergies and examined epitope sequences in this allergen. In the present study, we aimed to examine epitope sequences in the Per a 10 allergen. for this purpose, the Per a 10 gene was cloned and expressed in Escherichia coli (E. coli) systems. Our results revealed that 9 out of 16 (56.3%) sera from patients with American CR allergies reacted to Per a10, as assessed by ELISA, confirming that Per a 10 is a major allergen of the American CR. Our results also revealed that the expression of CD63 and CCR3 on passively sensitized basophils (obtained sera of patients with American CR allergies) was increased by approximately 2.3-fold, indicating that recombinant Per a 10 is functionally active. In addition, 3 immunoinformatics tools, namely the DNAStar Protean system, the Bioinformatics Predicted Antigenic Peptides (BPAP) system and the BepiPred 1.0 server were used to predict the peptides and the results revealed 8 peptides (2-12, 55-67, 98-120, 125-133, 149-160, 170-182, 201-208 and 223-227) as potential B cell epitopes of the Per a 10 allergen. Moreover, Per a 10 was predicted to have 3 T cell epitope sequences, namely 83-92, 139-147 and 162-170. The findings of our study on the CR allergen may prove to be useful in the development of peptide-based vaccine for the prevention and/or treatment of CR allergies.

Mast cells are well established effector cells of type I hypersensitivity reactions such as allergic rhinitis. However, recent studies have suggested that activated mast cells enhance local immunoglobulin E (IgE) synthesis in the nasal mucosa of allergic rhinitis patients. Therefore, we hypothesized that non-immunological mast cell activators may have the potential to enhance local IgE synthesis. Here, we examined the effect of compound 48/80 (C48/80), a mast cell activator, on IgE and immunoglobulin G (IgG) synthesis. Female Balb/c mice were intranasally administered a mixture of ovalbumin (OVA) (1-10 µg/nose) and C48/80 (1-100 µg/nose) on days 0, 7, 14 and 21 and on consecutive days from day 28 to day 42. Intranasal administration of C48/80 with OVA increased serum OVA-specific IgE and IgG. Double staining with fluorescent-labeled OVA and fluorescent-labeled IgE- or IgG-specific antibody demonstrated the presence of OVA-specific IgE- or IgG-producing cells in the nasal mucosa of sensitized mice. Moreover, intranasal administration of C48/80 with OVA increased the nasal mucosal interleukin (IL)-4 level and enhanced the OVA-induced symptom of sneezing. These results suggested that simultaneous activation of mast cells with antigen exposure enhances local IgE and IgG synthesis.

Allergens extracts from cats and dogs dander were prepared by extraction, followed by purification and fractionation by gel filtration. One major peak was obtained from cat dander with a molecular weight 35KDa, where as two major peaks were obtained from dog dander with a molecular weight 21 and 18 KDa. Total and specific IgE ELISA test was performed on 137 patient’s sera samples. The rate of the total IgE positive ELISA results was (72.99%). From the total IgE positive, it was found that the rate of the specific IgE positive ELISA results was 49% in case of patients examined with cat dander and 29% in patients examined with dog dander. There was significant difference (P

Mast cells (MCs) were first described by Paul Ehrlich as well fed granular cells that stain metachromatically. Today MCs are regarded as multifunctional, granulated, tissue-dwelling cells distributed in the perivascular spaces and connective tissues of every major organ of the body. Their long recognized phenotypic diversity might be associated not only with their anatomic distribution and mediator repertoire, but also with their functional characteristics related to the regulation of effector pathways. In addition to their historical involvement in type I hypersensitivity response, MCs have emerged as versatile effector cells with functional diversity and homeostatic functions in non-IgE-mediated inflammatory responses, autoimmunity, bidirectional interactions with the neuroendocrine circuit, the urinary, gastrointestinal, cardiovascular and endocrine systems, in metabolism and malignancy. Thus, MCs appear to receive, integrate and transmit a wide range of signals in their microenvironment, coordinated by the differential release of their pro-inflammatory and anti-inflammatory granular mediators. Understanding the heterogeneity of this complex cellular communication may provide a tool for selective pharmacological intervention directed to specific MC subsets.

Background Corticosteroid contact allergy is not uncommon. The diagnosis can be made with either patch testing or intradermal (ID) testing. In view of a few problems that have been encountered with patch testing, patch testing is considered inferior to ID testing. The reported reproducibility of positive patch-test results in the literature ranges from 47 to 98%. Objectives This study was conducted to (1) determine the reproducibility of patch testing with topical steroid preparations and their clinical relevance, (2) correlate positive results with ID testing, (3) address the issue of cross-reactivity between different steroid groups, and (4) identify the percentage of positive reactions to preservatives and vehicles used in commercial topical steroids. Methods A total of 19 patients with positive patch-test reactions to steroids from 1995 to 2004 were identified. Atopic patients and patients with type I hypersensitivity were excluded. The patients were patch-tested with a steroid series, select commercial steroid products, and vehicles and preservatives used in these preparations. The same patients were subjected to ID testing with select steroids. Readings were done on days 2, 5, and 7. ID testing was also performed on 9 control patients. Results Tixocortol-21-pivalate is the most common steroid allergen (68%). The reproducibility of patch testing with topical steroid preparations ranged from 66 to 100%. Reactions to both ID testing and patch testing occurred in 16 patients (89%); 1 patient reacted to patch testing and 1 other reacted to ID testing. Formaldehyde and formaldehyde releasers accounted for the majority of reactions in the vehicles and preservatives group. Conclusion Patch testing is sufficient in diagnosing allergic contact dermatitis from topical steroids. Testing with commercial products is not a good screen for steroid allergy. The most common cross-reactions were between group A (hydrocortisone-type) corticosteroids and group D2 corticosteroids (composed of labile esters, with a long-chain ester at C17 and possibly C21).

All chemotherapy agents can cause hypersensitivity reactions, which have limited the used of critical drugs in very sick patients for fear of inducing a more severe reaction and possibly death. The choice of an alternative chemotherapy regimen is often limited by tumor sensitivity and, because of the increasing number of cancer survivors, exposure to multiple courses of the same or similar chemotherapy agents. Increased exposures lead to sensitization and to hypersensitivity reactions in an increasing patient population. The need to offer first line therapy after cancer recurrence has spurred the clinical development of rapid desensitizations, which allow patients to be treated with medications to which they have presented hypersensitivity reactions. Desensitization protocols are available to treat hypersensitivity reactions to most chemotherapy agents including taxenes, platinums, doxorubicin, monoclonal antibodies and others, by gradual re-introduction of small amounts of drug antigens up to full therapeutic doses. Candidate patients include those who present mild to severe type I hypersensitivity, mast cell/IgE dependent, reactions during the chemotherapy infusion or shortly after. Symptoms include pruritus, flushing, urticaria, angioedema, respiratory and gastrointestinal distress, changes in blood pressure including hypotension, and shock with anaphylaxis. Associated musculoskeletal symptoms and pain can be present in patients reacting to taxenes as in anaphylactoid reactions, in which mast cell/IgE mechanisms cannot be demonstrated. There is now strong evidence that anaphylactoid reactions are amendable to treatment with the same rapid desensitization protocols as for type I hypersensitivity reactions. Initial rapid desensitizations should only be performed in settings with one on one nurse-patient care and where resuscitation personnel and resources are readily available. Temporary tolerization is achieved in a few hours. After the first desensitization, standard protocols are available for safe, repeated desensitizations in outpatient settings with similar conditions, which not only provides flexibility, but allows patients to remain in clinical studies. Breakthrough symptoms are less severe than the initial hypersensitivity reaction in all series reviewed, and deaths have not been reported. The aim of this review is to familiarize the medical community with the type of hypersensitivity reactions amendable to rapid desensitization and to review protocols for chemotherapy desensitization that can be used for most chemotherapy agents. Few studies have measured the cancer response to the chemotherapy agents delivered through rapid desensitizations. One patient population in which 26 patients were desensitized to carboplatin and 16 to paclitaxel had similar rates of remission as for non-desensitized patients. Education of nurses, pharmacists, oncology and allergy specialists will lead to the universal use of rapid desensitization protocols for all cancer patients with hypersensitivity reactions to chemotherapy agents. Basic research is needed to uncover the cellular and molecular mechanisms underlying the temporary tolerization induced by rapid desensitization, so that pharmacological interventions can improve its safety and efficacy.

Cardiac anaphylaxis refers to the functional and metabolic changes in the heart caused by the anaphylactic release of histamine and vasoactive products of arachidonic acid cascade by mast cells and basophils. As in most type I hypersensitivity-based diseases, histamine plays a key role in the pathophysiology of cardiac anaphylaxis. In the heart, mast cell activation and histamine release are controlled by multiple endogenous mechanisms, including adrenergic neural control, histamine-dependent negative feedback operated through H2 receptors, and the endogenous generation of nitric oxide (NO) and carbon monoxide (CO). All these mechanisms can be targeted by substances that have revealed a clear-cut effect in blunting cardiac anaphylaxis in experimental animal models, and could be developed as potential, novel anti-anaphylactic drugs. In this article, we discuss new findings and significant trends related to this topic.

INTRODUCTION Although the tests could be done at any site, the proximal part of the flexor aspect of the forearm is Intradermal tests are widely used to support the conventionally used. This site can be conveniently diagnosis of dermatological and nondermatological exposed and the skin of the proximal area is more diseases. They are mainly indicated for the detection sensitive than the distal. of immediate (Type I hypersensitivity) and delayed type hypersensitivity (DTH, Type IV hypersensitivity) INTERPRETATION OF INTRADERMAL TESTS towards exogenous or endogenous antigens. Intradermal tests for the diagnosis of infectious The optimal time for reading the reaction depends diseases in relevance to dermatovenereology are upon the pharmacological agent used for the test discussed in this section. and the type of immunological reaction to be observed. Intradermal tests for the detection of DTH Intradermal tests for the diagnosis of infectious are read at 48h, although they can be read as early diseases are listed in Table 1. They are indicated to as 12h and as late as four days. (The lepromin test detect DTH to organisms or their antigens. is read at four weeks and depends on the formation of a granuloma, which is a measure of cell-mediated Before undertaking intradermal test, it is advisable to immunity.) The size of the induration is more stop or avoid systemic steroids or immunosuppressive important than erythema while interpreting Type agents at least three days before the procedure as IV hypersensitivity. moderate to large doses of corticosteroids may inhibit a DTH reaction.

Urticaria is dermal edema resulting from vascular dilatation and leakage of fluid into the skin in response to molecules released from mast cells. The major preformed mediator histamine produces a prototypic, short-lived urticaria. However, the clinical spectrum and pattern of lesions indicate that other molecules, including prostaglandins, leukotrienes, cytokines, and chemokines, produced at different times after mast cell activation contribute to the polymorphism of this symptom and the variable evolution of this disease. It is a common practice to distinguish immunological and nonimmunological urticaria. Immunological urticaria is a hypersensitivity reaction mediated by antibodies and/or T-cells that results in mast cell activation. Although immunoglobulin (Ig)E-mediated type I hypersensitivity (HS) was long postulated to be the major immunological pathway associated with mast cell activation, interaction between IgE-bound mast cells and allergens is unlikely to be the mechanism by which urticaria develops in most patients. It is now well established that urticaria may result from the binding of IgG auto-antibodies to IgE and/or to the receptor for IgE molecules on mast cells, thus corresponding to a type II HS reaction. These auto-immune urticarias represent up to 50% of patients with chronic urticaria. Mast cell activation can also result from type III HS through the binding of circulating immune complexes to mast cell-expressing Fc receptors for IgG and IgM. Finally, under certain circumstances, T-cells can induce activation of mast cells, as well as histamine release (type IV HS). Nonimmunological urticarias result from mast cell activation through membrane receptors involved in innate immunity (e.g., complement, Toll-like, cytokine/chemokine, opioid) or by direct toxicity of xenobiotics (haptens, drugs). In conclusion, urticaria may result from different pathophysiological mechanisms that explain the great heterogeneity of clinical symptoms and the variable responses to treatment.

Type I hypersensitivity reactions are in constant progression in industrialized countries. The physiopathologic mechanism of these diseases implicates the production of specific immunoglobulin (Ig)E to allergenic molecules, their binding to the Fcepsilon receptor on the surface of mast cells and basophils, and the release of inflammatory mediators when allergens are introduced into the body and crosslink with the IgE bound to the cell surface. An allergen is defined as a molecule that induces the production of, and binds to, IgE. The identification of the allergenic molecules is an important goal to improve diagnosis and treatment of allergy. This characterization aims to extract proteins from the allergenic source, to analyze IgE specificity by immunoblotting and to identify the proteins that bind IgE.

SummaryThe study of the singular hypersensitivity reactions to Anisakis simplex (A.s) proteins, may help us to undestand many of the unknown immune interactions between helmiths infections and allergy. We have developed a murine model of allergy to A. simplex, that mimics human A. simplex allergy to study the specific aspects of anaphylaxis induced by parasites. Male C3H/HeJ mice were intraperitoneally sensitized to A. simplex. Mice were then intravenous or orally challenged with A. simplex. Antigen-specific immunoglobulins, polyclonal IgE, anaphylactic symptoms, plasma histamine levels and cytokine profiles were determined. Comparative IgE immunoblot analyses were also performed. Specific IgE, IgG1 and IgG2a were detected in sensitized mice since week 3. Polyclonal IgE raised and peaked with different kinetics. Intravenous A. simplex challenge produced anaphylaxis in mice, accompanied by plasma histamine release. Oral A. simplex challenge in similarly sensitized mice did not caused symptoms nor histamine release. Numerous A. simplex allergens were recognized by sensitized mouse sera, some of them similar to human serum. The A. simplex stimulated splenocytes released IL-10, IFN-γ, IL-4, IL-13 and IL-5. We describe a new animal model of anaphylaxis. It exhibits characteristics of type I hypersensitivity reactions to Anisakis simplex similar to those observed in allergic humans. Different responses to i.v. or oral A. simplex challenges emerged, which did not reflect a window tolerization period. The cytokine profile developed (mixed Th1/Th2 pattern) differed from the observed in classical models of anaphylaxis or allergy to food antigens. This model may permit to investigate the peculiar allergic reactions to parasitic proteins.

Rifampin is commonly used as a first-line anti-tuberculosis drug, but it can induce a serum sickness-like reaction or anaphylaxis. However, it is possible for 1 drug antigen to induce 2 or more simultaneous immunologic reactions. Here, we report a case of a serum-sickness-like reaction and anaphylaxis induced concurrently by rifampin. A 25-year-old male presented with high fever and a maculopapular rash with vesicles on the hands, which developed 2 weeks following regular administration of anti-tuberculosis drugs for tuberculous meningitis, including rifampin. Elevated liver enzymes, peripheral neuropathy, and decreased serum C3 and C4 levels were found. Interestingly, these symptoms were accompanied by severe hypotension. A serum-sickness-like reaction was considered after excluding other potential causes for the fever. A drug provocation test showed that the fever developed after oral administration of rifampin, suggesting that rifampin was the cause of the allergic reaction. However, hypotension, epigastric discomfort, and diarrhea also accompanied these symptoms, indicating that IgE-mediated type I hypersensitivity could be part of the serum sickness-like reaction. An intradermal skin test clearly showed an immediate positive reaction to rifampin. This case was diagnosed as concurrent serum-sickness-like reaction and anaphylaxis induced by rifampin. One drug may therefore induce combined allergic reactions via 2 or more simultaneous hypersensitivity responses.

Objective The purpose of this study was to determine whether type I hypersensitivity can induce preterm labor and delivery that may be prevented by the administration of an H 1 receptor antagonist or a mast-cell stabilizer. Study design At days 40 through 50 of gestation, ovalbumin-sensitized guinea pigs that had not been treated or had been pretreated with an H 1 receptor antagonist (ketotifen) or a mast-cell stabilizer (cromolyn sodium) were challenged with either ovalbumin or saline solution. Nonsensitized guinea pigs were challenged with ovalbumin. Results The duration of gestation was significantly shorter in sensitized animals that were challenged with ovalbumin than in the other groups. Pretreatment with ketotifen significantly increased the duration of pregnancy in sensitized animals, compared with untreated animals. Cromolyn sodium had no effect. Conclusion An allergic reaction can induce premature labor/delivery, and pretreatment with histamine H 1 receptor antagonist can prevent it. These observations provide evidence of a novel mechanism of disease for premature labor and delivery.

Mosquito bites in humans are characterized by an immediate wheal-and-flare type I hypersensitivity response, followed by a delayed type IV papular reaction approximately 24 h later. An intense pruritic reaction may accompany all phases of the bite. Prophylactically administered oral second-generation antihistamines inhibit the immediate histamine induced wheal-and-flare in skin, and some studies show that they are also useful in alleviating delayed bite symptoms. Topical antihistamines have not been documented to be useful in treatment; however, topical ammonium solution and other common allergic reaction remedies are promising as after-bite treatments. This review assesses the current evidence analyzing the efficacy of prophylactic, oral, second-generation antihistamines as well as topical therapies for mosquito bites.

Due to IgE cross-reactivity, birch pollen-allergic individuals frequently develop type I hypersensitivity reactions to celery tuber. We evaluated the T cell response to the major allergen in celeriac, Api g 1, and the cellular cross-reactivity with its homologous major allergen in birch pollen, Bet v 1. Api g 1-specific T cell lines (TCL) and clones (TCC) were established from peripheral blood mononuclear cells of allergic patients. Epitope mapping of Api g 1 with overlapping Api g 1-derived peptides revealed one dominant T cell-activating region, Api g 1(109-126). TCL and TCC generated with Api g 1 cross-reacted with the birch pollen allergen and, although initially stimulated with the food allergen, cellular responses to Bet v 1 were stronger than to Api g 1. Epitope mapping with Bet v 1-derived peptides revealed that T cells specific for several distinct epitopes distributed over the complete Bet v 1 molecule could be activated by Api g 1. Bet v 1(109-126) was identified as the most important T cell epitope for cross-reactivity with Api g 1. This epitope shares 72% amino acid sequence similarity with the major T cell-activating region of the food allergen, Api g 1(109-126). Our data provide evidence that humoral as well as cellular reactivity to the major celery allergen is predominantly based on cross-reactivity with the major birch pollen allergen. The activation of Bet v 1-specific Th2 cells by Api g 1, in particular outside the pollen season, may have consequences for birch pollen-allergic individuals.

Ficus benjamina is a plant very often used for indoor decorations that can generate allergies, e.g. rhinoconjunctivitis, urticaria and Quinke's edema as well as anaphylactic reactions. We report the case of a patient withhypersensitivity to Ficus benjamina without cross-reactivity to Natural Rubber Latex (NRL) or several fruits, like mango, banana and spinach, but with cross-reactivity to fig. The hypersensitivity to Ficus benjamina was investigated by means of the prick test, the determination of specific IgE antibodies, the cellular antigen stimulation test (CAST) and Westemblots. A self-produced Ficus benjamina extract, a Ficus benjamina extract from Allergopharma, extract of Hevea brasiliensis and extracts of several fruits were used in the prick tests as well as in the CAP and CAST experiments. CAP inhibition assays were carried out to study a suspected cross-reactivity of Ficus benjamina to NRL and several fruits, respectively. The hypersensitivity to Ficus benjamina was clearly demonstrated. Inhibition assay showed the inhibition of the specific IgE antibody up to 95%, and 82% by the self-produced Ficus benjamina extract and the commercial Ficus benjamina, respectively. Neither sensitization nor cross-reactivity to Hevea brasiliensis and several fruit proteins could be found, apart from cross-reactivity to fig. In our patient, an isolated type I hypersensitivity to Ficus benjamina with cross-reactivity to fig could be found, but without cross-reactivity to NRL. The Ficus benjamina protein seems to become an important indoor allergen with increasing significance.

The administration of killed Propionibacterium acnes suspension to mice enhances macrophage phagocytic and tumoricidal activities, have an adjuvant effect to antibody response and increases resistance to infection. Recent reports demonstrated that P. acnes treatment promotes IL-12 and IL-18 synthesis in mice inducing IFN-gamma release, enhancement of IgG2a switch and inhibition of Th2 cell expansion. These findings led us to investigate whether P. acnes could modulate hypersensitivity type I reaction observed in a murine model. Animals were implanted with heat coagulated hen's egg white (HEW) into the subcutaneous tissue, followed by OVA-challenge in the footpad. The observed reaction was characterized by elevated Th2 cytokine levels, especially IL-4 and increase in eosinophil infiltration as occurs in the late phase reaction (LPR) of type I hypersensitivity, a pattern observed in allergic asthma in human. Two different biological effects were induced by killed P. acnes depending on the experimental protocol used. When mice were treated with one dose of P. acnes per week during 3 weeks and the last dose administrated at the same time of HEW implantation, a strong adjuvant effect on type I hypersensitivity reaction with intense eosinophilic infiltration was observed. On the other hand, when the HEW implant was made 1 week after the administration of the last dose of P. acnes, animals developed a typical delayed type hypersensitivity reaction, and a cytokines pattern characteristic of the Th1 immune response.

Latex hypersensitivity manifests itself most commonly with contact urticaria. In this study, we investigated the frequency of latex hypersensitivity as a possible aetiological factor in patients with chronic urticaria (CU) and compared latex hypersensitivity of CU patients (n = 50) with that of rubber factory workers (n = 50) and healthy controls (n = 50). Prick test with latex and fruit extracts and determination of latex-specific immunoglobulin E (IgE) were performed. As a risk factor, contact dermatitis due to rubber additives was tested by patch test. Latex hypersensitivity was detected in 14% of CU patients, 12% of rubber factory workers and 12% of healthy controls (P > 0.05). Positive patch test with rubber additives was detected in 6% of CU and 4% of rubber factory workers. 3 of 7 CU patients had sensitivity to fruits in addition to latex hypersensitivity. In 1 patient with CU, the clinical complaints were found to be related to latex hypersensitivity. These findings suggest that the frequency of latex hypersensitivity in CU patients is no higher than that in healthy individuals. However, CU patients should be carefully asked about latex allergy, as we demonstrated that 1 of the CU patients had undiagnosed symptomatic latex allergy.

Anaphylaxis is a potentially life threatening, type I hypersensitivity reaction which can occur within seconds to minutes after exposure to an allergen. Sulfites have been implicated in causing such reactions with symptoms ranging from mild to potentially life threatening. Here we present a patient who had an anaphylactic reaction secondary to exposure to sulfites found in sparkling water.

Mast cells and immunoglobulin E (IgE) are most familiar as the effectors of type I hypersensitivity reactions including anaphylaxis. It is becoming clear however that this pair has important immunomodulatory effects on innate and adaptive cells of the immune system. In this purview, they act as endogenous adjuvants to ignite evolving immune responses, promote the transition of allergic disease into chronic illness, and disrupt the development of active mechanisms of tolerance to ingested foods. Suppression of IgE-mediated mast cell activation can be exerted by molecules targeting IgE, FcɛRI, or signaling kinases including Syk, or by IgG antibodies acting via inhibitory Fcγ receptors. Recent reports indicate that such interventions have promise in the development of strategies to treat allergic disease.

RESUMO As alergias oculares englobam uma série de doenças inflamatórias da superfície ocular, causadas por diferentes mecanismos de hipersensibilidade. Acometem aproximadamente 20% da população e podem ser classificadas em formas mediadas por hipersensibilidade tipo I (CAS, CAP), tipo I e IV (CCV, CCA) e tipo IV (BCC, CPG). As formas mais prevalentes são CAS e CAP. As formas crônicas (CCV, CCA) estão mais frequentemente relacionadas a complicações e comprometimento da função visual decorrentes do processo inflamatório e consequente remodelação da superfície ocular. Comorbidades como olho seco e ceratocone podem estar presentes. O tratamento envolve diagnóstico e afastamento dos fatores etiológicos envolvidos, uso de drogas anti-inflamatórias que atuem na ação de linfócitos Th2, eosinófilos, mastócitos e células dendríticas Avanços no conhecimento da ativação e tráfego de células do sistema imune têm sido promissores na perspectiva de novas abordagens terapêuticas. ABSTRACT Ocular allergies encompass a number of inflammatory diseases in the ocular surface which have different hypersensitivity mechanisms and occur in 20% of population. They can be classified as being type I hypersensitivity mediated (PAC, SAC), type I and IV (VKC, AKC) and type IV (BKC, GPC). The most prevalent forms are PAC and SAC. The chronic presentations are mostly related to visual impairment due to remodeling in the ocular surface caused by chronic inflammation. Dry eye disease and keratoconus are comorbidities observed in severe cases. The management is based on accurate diagnosis, avoidance of etiological factors and the rational use of drugs that control the inflammatory events caused by Th2 driven. The advances in knowledge on activation and traffic of immune cells are providing new drugs and many perspectives on different approaches.

The accurate diagnosis of hypersensitivity to natural rubber latex is the initial step in the effective management of individuals with latex allergy and in ensuring the quality of epidemiologic studies. The diagnostic algorithm used in the evaluation of an individual with suspected latex allergy begins with a comprehensive clinical history during which risk factors (atopy, food allergies, hand dermatitis) and temporal relationships between symptoms and natural rubber product exposure are identified. If type IV hypersensitivity is suspected because of the delayed nature (hours to days) and confinement of symptoms to the skin-latex product contact areas, patch testing can be conducted to confirm the presence of activated T cells with specificity for rubber chemicals. If type I hypersensitivity is suspected because of ocular, upper and lower airway, and/or systemic symptoms that have rapid onset (minutes) after a definable latex exposure, a confirmatory skin or blood test for IgE antibody may be conducted to verify a state of sensitization within the individual. The definitive diagnosis would then be made only after consideration of the individual's clinical history and confirmatory in vivo and/or in vitro laboratory test results. If discordance remains between highly convincing latex-associated symptoms as identified in the history and repetitively negative confirmatory IgE antibody test results, then one of several types of in vivo provocation tests may be performed for adjudication. This overview examines the current state of the art in both in vivo and in vitro diagnostic methods for latex-specific IgE antibody detection in skin and blood. The performance, advantages, and limitations of each diagnostic method are compared.

Objectives. To describe the types of allergic responses which can be seen among employees working in the chemical industry. Methods. This is a review of current literature. Results. Although allergic reactions are more frequently attributed to protein exposure, there is increasing evidence that certain chemicals can produce allergic disease for each of the four types of allergic reactions described by Gell and Coombs. Type I hypersensitivity reactions are seen with certain low-molecular-weight chemicals. Type II hypersensitivity reactions, exemplified by Goodpasture's syndrome, have been associated with certain metal exposures. Low-molecular-weight chemicals have been reported to cause type III hypersensitivity reactions such as those seen in hypersensitivity pneumonitis. Finally, the majority of type IV reactions are characterized by allergic contact dermatitis, although some hard metals have produced type IV pulmonary disease. Several predictive tests are now available to screen chemicals for pulmonary and skin sensitizing capability. Conclusions. Chemicals have been implicated in producing a wide variety of hypersensitivity reactions. Screening tests can be of use in managing the risks of these chemicals.

This study investigated the capacity of conjugated linoleic acids (CLA) to reduce ex vivo antigen-induced release of eicosanoids in a type I hypersensitivity model. Guinea pigs were fed a diet containing 0.25% safflower oil (control) or 0.25% CLA [43% trans( t)10, cis ( c)12; 41% c9, t11/ t9, c11 18:2] for 2 wk before and during sensitization to ovalbumin (OVA). Lungs, tracheas, and bladders were incubated in physiological saline solution (PSS) for 1 h (basal mediator release) and challenged with OVA (0.01 g/l PSS) for 1 h (mediator release in response to antigen). Eicosanoids were quantified by HPLC/tandem mass spectrometry or enzyme immunoassay. CLA feeding resulted in no change in basal release but decreased eicosanoid release from sensitized tissues in response to antigen challenge in the following manner: thromboxane B2, 6-keto-prostaglandin (PG)F1α, PGF2α, PGD2, PGE2by 57–75% in lung, 45–65% in trachea, and 38–60% in bladder; and leukotriene C4/D4/E4by 87, 90, and 50% in lung, trachea, and bladder, respectively. These data indicate that feeding CLA reduces lipid-derived inflammatory mediators produced by this type I hypersensitivity model.

Background It has been established that there are type I and type IV allergens in latex gloves. Objective The purpose of the study was to establish the prevalence of rubber glove-induced skin symptoms among health care workers in one Italian hospital. Methods Health care workers (n = 1584) were evaluated using a written questionnaire and 295 respondents with glove-induced skin symptoms were tested. We performed: skin prick test with latex glove extract and commercial latex, and environmental and food allergens; glove use test; patch tests with a rubber additive series; and RASTs. Results Hospital employees who used or had used latex gloves at work were 1294. Three hundred and sixteen (24.4%) reported glove-induced symptoms, namely, cutaneous symptoms in all the cases and non-cutaneous symptoms in 105 subjects (8.1%). Twenty-seven of the 295 symptomatic employees tested (9.1%) were latex sensitive. Thirty-one patients (10.5%) exhibited positive patch test to rubber-related allergens. The most positive readings were obtained from the Thiuram mix and the Carba mix, with 12 and 9 positivities, respectively. The risk factors for latex skin sensitization were: a previous history of atopy and asthma; history of surgery; pre-existing hand dermatitis; work-related symptoms; and positive skin tests to common inhalant and certain foods (P

Background: Maternal exposure to environmental ubiquitous allergens could exert an influence on the newborn’s immune repertoire and the later development of allergy. The aim of this study was to investigate the effects of maternal immunization with Dermatophagoides pteronyssinus (Dp) on the hypersensitivity response and IgG subclass production in offspring using a murine model. Methods: A/Sn mice were immunized with Dp before mating with normal A/Sn males. Diaplacental serum samples were collected from newborn mice delivered by cesarean section, and maternal milk samples were extracted from the stomachs of newborn mice. Groups of offspring 25 or 45 days old were Dp immunized and boosted on the 10th day after sensitization. The animals were bled 7 days after the booster. Results: High levels of anti-Dp IgG subclasses – mainly IgG1, but also IgG2a and IgG2b – were transmitted by immunized mice via the placenta to the offspring. In the milk from immunized mothers, significant levels of anti-Dp IgG subclasses and anti-Dp IgM and IgA antibodies were detected. Moreover, the increase in total IgA antibodies in the milk of the immunized females correlated with a significantly increased level of TGF-β1. TGF-β2 levels were markedly higher than the β1 isoform in the milk, although no difference was observed between the groups. When offspring from immunized mothers were sensitized at 25 days, a significant decrease in total and anti-Dp IgE antibodies as well as total and anti-Dp IgG1, IgG2a and IgG2b subclasses was observed compared to normal female offspring, whereas when offspring were sensitized at 45 days, both offspring groups showed similar levels of IgE and IgG subclasses. Conclusions: Our study showed that maternal immunization with Dp promotes the transference of specific antibodies and/or TGF-β, which can negatively modulate the allergic response in offspring, and suggests that maternal preexposure to allergen before mating can protect mice during the early phase.

Allergic reactions against GH are rare, and usually represented by the hypersensitivity type I (IgE-mediated). This type of reaction can be treated by desensitization. In this case report, we present a patient showing an allergic reaction soon after starting GH therapy mediated by immune complex (hypersensitivity type III reaction). In this condition, the attempt to perform the desensitization procedure can perpetuate immune complex deposition determining a life threatening renal and respiratory insufficiency.

Background Itch is a major symptom of allergic skin disease. Acupuncture has been shown to exhibit a significant effect on histamine-induced itch in healthy volunteers. We investigated the effect of acupuncture on type I hypersensitivity itch and skin reaction in a double-blind, randomized, placebo-controlled, crossover trial. Methods An allergen stimulus (house dust mite or grass pollen skin prick) was applied to 30 patients with atopic eczema before (direct effect) and after (preventive effect) two experimental approaches or control observation: acupuncture at points Quchi and Xuehai (verum acupuncture [VA], dominant side), ‘placebo-point’ acupuncture (PA, dominant side), no acupuncture (NA). Itch intensity was recorded on a visual analogue scale. After 10 min, wheal and flare size and skin perfusion (via LASER-Doppler) were measured at the stimulus site, and the validated Eppendorf Itch Questionnaire (EIQ) was answered. Results Mean itch intensity was significantly lower in VA (35.7 ± 6.4) compared to NA (45.9 ± 7.8) and PA (40.4 ± 5.8) regarding the direct effect; and significantly lower in VA (34.3 ± 7.1) and PA (37.8 ± 5.6) compared to NA (44.6 ± 6.2) regarding the preventive effect. In the preventive approach, mean wheal and flare size were significantly smaller in VA (0.38 ± 0.12 cm2/8.1 ± 2.0 cm2) compared to PA (0.54 ± 0.13 cm2/13.5 ± 2.8 cm2) and NA (0.73 ± 0.28 cm2/15.1 ± 4.1 cm2), and mean perfusion in VA (72.4 ± 10.7) compared to NA (84.1 ± 10.7). Mean EIQ ratings were significantly lower in VA compared to NA and PA in the treatment approach; and significantly lower in VA and PA compared to NA in the preventive approach. Conclusions Acupuncture at the correct points showed a significant reduction in type I hypersensitivity itch in patients with atopic eczema. With time the preventive point-specific effect diminished with regard to subjective itch sensation, whereas it increased in suppressing skin-prick reactions.

Little is known about the clinical and immunological changes in the nickel allergic patients with systemic symptoms. We aimed to evaluate T helper cell responses of patients with different clinical presentations due to nickel.Patients having various allergic symptoms and positive patch test results to nickel and 20 controls underwent skin prick tests with nickel. IL-10, IL-4, IL-5 and IFN-gamma were measured in the culture supernatants of PBMC stimulated by nickel during lymphocyte proliferation test (LTT).69 patients (56 female, mean age: 49.2 ± 13.1), 97% having nickel containing dental devices and 20 controls (8 female, mean age 34.9 ± 12.06) were evaluated. Skin prick tests with nickel were positive in 70% of the patients (p0.001), being significantly higher in the patients with urticaria/angioedema (p=0.02). The LTT stimulation index (p0.0001), IL-4 (p=0.002), IFN-gamma (p=0.01), IL-5 (p=0.04) and IL-10 (p=0.003) were higher in the patient group. LTT stimulation index, IL-4 and IL-10 were significantly elevated in patients having urticaria, angioedema and respiratory symptoms when compared to those who had only oral symptoms or systemic dermatitis (p=0.004, p=0.002 and p=0.01, respectively).This study suggests the presence of Type I hypersensitivity in addition to a Type IV immune reaction in patients with chronic systemic symptoms related to nickel. Nickel containing dental alloys and oral nickel intake seem to trigger systemic symptoms in previously nickel sensitized patients.

In this study we evaluated the effect chronic helminth infection has on allergic disease in mice previously sensitized to ovalbumin (OVA). Ten weeks of infection with Litomosoides sigmodontis reduced immunological markers of type I hypersensitivity, including OVA-specific IgE, basophil activation, and mast cell degranulation. Despite these reductions, there was no protection against immediate clinical hypersensitivity as measured by changes in vascular permeability following intradermal OVA challenge. However, late phase ear swelling, due to type III hypersensitivity, was significantly reduced in chronically infected animals. Immune complexes visualized in the ear were slightly larger in the infected group. Levels of total IgG2a, OVA-specific IgG2a, and OVA-specific IgG1 were all reduced in the setting of infection. These reductions were likely due to increased antibody catabolism as ELISPOT assays demonstrated that infected animals do not have suppressed antibody production. Ear histology 24 hours after challenge showed infected animals have reduced cellular infiltration in the ear, with significant decreases in numbers of neutrophils and macrophages. Consistent with this finding, infected animals had significantly fewer neutrophil-specific chemokines CXCL1 and CXCL2 in the ear following challenge. Additionally, in vitro stimulation with immune-complexes resulted in significantly less CXCL1 and CXCL2 production by eosinophils from chronically infected mice. Expression of FcyRI was also significantly reduced on eosinophils from infected animals. Finally, we found that L. sigmodontis infection decreased anti-ds DNA autoantibodies and prevented mesangial expansion in mice with previously established systemic lupus erythematosus. These data indicate that chronic filarial infection suppresses eosinophilic responses to antibody-mediated activation and has the potential to be used as a therapeutic for pre-existing hypersensitivity diseases.

Allergy is an abnormal immune response to an allergen. Type I hypersensitivity is an immunoglobulin (Ig) E-mediated allergic disorder. Fructus piperis is derived from the ripe fruit of the pepper, which is widely used as a spice in human diets and is also administered as a medicine in many countries. Piperine has been shown to have anti-oxidant, anti-depressant, anti-tumor, and anti-inflammatory activities. However, the effect of piperine on IgE-mediated allergic responses has not been reported. Here, the rat basophilic leukemia cells by membrane chromatography (RBL-2H3/CMC) coupled to high performance liquid chromatography/mass spectrometry (HPLC/MS) to discover and identify piperine can bind to RBL-2H3 cell membranes. Piperine inhibited the expression of cytokines, and the release of both β-hexosaminidase and histamine, which could be stimulated by antigen in RBL-2H3 mast cells. We found that the levels of intracellular Ca(2+) also decreased. Furthermore, RT-PCR showed that the mRNA expression levels of IL-4, IL-13, and TNF-α were significantly suppressed by piperine. The inhibitory effect of piperine on IgE-mediated degranulation and cytokine production by RBL-2H3 cells may be caused by the inhibition of IgE-mediated signaling pathways, including the phosphorylation of Lyn, p38, Erk, and Ras. In summary, piperine can inhibit antigen-induced allergic reactions that control degranulation.

R.J. is a 51-year-old man who has had type 2 diabetes for 18 years. Because of poor metabolic control with oral agents, he was prescribed a premixed formulation of regular and NPH insulin (Novo Nordisk, Madrid, Spain). Two weeks later, he developed pruritic lesions at the injection site. As treatment continued, lesions of similar characteristics developed in previous injection sites. He was switched to a different brand of the same mixture of insulins (Eli Lilly, Madrid, Spain). He presented to the emergency department when, after injecting a dose of insulin, he developed nausea, labial edema, shortness of breath, and urticaria lesions progressing from trunk to extremities. He improved rapidly with oral antihistamines and intravenous corticosteroids. R.J. was then evaluated by the Allergology Department and was diagnosed with having experienced an anaphylactic reaction. Three days later, blood samples were taken for laboratory testing (Table 1). Skin prick and intradermal tests revealed sensitization to all insulins tested: regular, NPH, and premixed formulations (Novo Nordisk and Eli Lilly), as well as lispro, aspart, glulisine, glargine, detemir, aspart/aspart protamine, and lispro/lispro protamine. Results were considered positive when the diameter of the wheal was ≥ 3 mm larger than the negative control. Saline solution and histamine were used as negative and positive controls, respectively. Tests against other potential allergens were not deemed necessary because he showed reaction to all the preparations tested, which had different excipients. A diagnosis of type I hypersensitivity to insulin was established. R.J. underwent a rapid subcutaneous desensitization to the initial mixture of insulins (regular and NPH …

A subset of coronary arterial dissections is associated with eosinophilic coronary periarteritis (ECPA); however, the pathogenesis of the process remains unclear. Mast cells normally reside in coronary arterial adventitia and are known mediators of eosinophilic inflammatory conditions such as type I hypersensitivity reactions. We report two cases in which coronary arterial dissection with ECPA was detected at autopsy. Tryptase, CD68, CD4, CD8, and CD1a immunohistochemical staining was performed to better characterize inflammation. While eosinophils represented a prominent periadventitial inflammatory cell, there were slightly more lymphocytes: CD4/CD8 ratios were within expected reference ranges. There were moderate numbers of macrophages, and few neutrophils or dendritic cells. Numbers of mast cells in dissected versus nondissected sections were compared: adventitial mast cell densities were threefold higher in dissected portions and showed a trend toward increased degranulation. These findings suggest that mast cells may play a role in orchestrating inflammation in cases of ECPA.

Ocular allergic disease affects not only the conjunctivae but also surrounding structures including the eyelids. Allergic diseases of the eyelid include atopic dermatitis, contact dermatitis, and urticaria/angioedema. They must be differentiated from nonallergic eyelid diseases. Allergic diseases of the conjunctivae comprise a spectrum of disorders from common, non-sight-threatening conditions such as seasonal allergic conjunctivitis, perennial allergic conjunctivitis, and giant papillary conjunctivitis to less common and potentially sight-threatening diseases such as vernal keratoconjunctivitis and atopic keratoconjunctivitis. Each of these conditions is mediated primarily by type I hypersensitivity reactions. The clinical manifestations, differential diagnosis, and treatment of these conditions are reviewed in this article.