IgE and anaphylaxis specific to the carbohydrate alpha-gal depend on IL-4.

BACKGROUND: Alpha-gal (Galα1-3Galß1-4GlcNAc) is a carbohydrate with the potential to elicit fatal allergic reactions to mammalian meat and drugs of mammalian origin. This type of allergy is induced by tick bites, and therapeutic options for this skin-driven food allergy are limited to the avoidance of the allergen and treatment of symptoms. Thus, a better understanding of the immune mechanisms resulting in sensitization through the skin is crucial, especially in the case of a carbohydrate allergen for which underlying immune responses are poorly understood. OBJECTIVE: We aimed to establish a mouse model of alpha-gal allergy for in-depth immunologic analyses. METHODS: Alpha-galactosyltransferase 1-deficient mice devoid of alpha-gal glycosylations were sensitized with the alpha-gal-carrying self-protein mouse serum albumin by repetitive intracutaneous injections in combination with the adjuvant aluminum hydroxide. The role of basophils and IL-4 in sensitization was investigated by antibody-mediated depletion. RESULTS: Alpha-gal-sensitized mice displayed increased levels of alpha-gal-specific IgE and IgG1 and developed systemic anaphylaxis on challenge with both alpha-gal-containing glycoproteins and glycolipids. In accordance with alpha-gal-allergic patients, we detected elevated numbers of basophils at the site of sensitization as well as increased numbers of alpha-gal-specific B cells, germinal center B cells, and B cells of IgE and IgG1 isotypes in skin-draining lymph nodes. By depleting IL-4 during sensitization, we demonstrated for the first time that sensitization and elicitation of allergy to alpha-gal and correspondingly to a carbohydrate allergen is dependent on IL-4. CONCLUSION: These findings establish IL-4 as a potential target to interfere with alpha-gal allergy elicited by tick bites.

Creation of a pandemic memory by tracing COVID-19 infections and immunity in Luxembourg (CON-VINCE).

BACKGROUND: During the COVID-19 pandemic swift implementation of research cohorts was key. While many studies focused exclusively on infected individuals, population based cohorts are essential for the follow-up of SARS-CoV-2 impact on public health. Here we present the CON-VINCE cohort, estimate the point and period prevalence of the SARS-CoV-2 infection, reflect on the spread within the Luxembourgish population, examine immune responses to SARS-CoV-2 infection and vaccination, and ascertain the impact of the pandemic on population psychological wellbeing at a nationwide level. METHODS: A representative sample of the adult Luxembourgish population was enrolled. The cohort was followed-up for twelve months. SARS-CoV-2 RT-qPCR and serology were conducted at each sampling visit. The surveys included detailed epidemiological, clinical, socio-economic, and psychological data. RESULTS: One thousand eight hundred sixty-five individuals were followed over seven visits (April 2020-June 2021) with the final weighted period prevalence of SARS-CoV-2 infection of 15%. The participants had similar risks of being infected regardless of their gender, age, employment status and education level. Vaccination increased the chances of IgG-S positivity in infected individuals. Depression, anxiety, loneliness and stress levels increased at a point of study when there were strict containment measures, returning to baseline afterwards. CONCLUSION: The data collected in CON-VINCE study allowed obtaining insights into the infection spread in Luxembourg, immunity build-up and the impact of the pandemic on psychological wellbeing of the population. Moreover, the study holds great translational potential, as samples stored at the biobank, together with self-reported questionnaire information, can be exploited in further research. TRIAL REGISTRATION: Trial registration number: NCT04379297, 10 April 2020.

High-dimensional immune profiles correlate with phenotypes of peanut allergy during food-allergic reactions.

BACKGROUND: Food challenges carry a burden of safety, effort and resources. Clinical reactivity and presentation, such as thresholds and symptoms, are considered challenging to predict ex vivo. AIMS: To identify changes of peripheral immune signatures during oral food challenges (OFC) that correlate with the clinical outcome in patients with peanut allergy (PA). METHODS: Children with a positive (OFC+ , n = 16) or a negative (OFC- , n = 10) OFC-outcome were included (controls, n = 7). Single-cell mass cytometry/unsupervised analysis allowed unbiased immunophenotyping during OFC. RESULTS: Peripheral immune profiles correlated with OFC outcome. OFC+ -profiles revealed mainly decreased Th2 cells, memory Treg and activated NK cells, which had an increased homing marker expression signifying immune cell migration into effector tissues along with symptom onset. OFC- -profiles had also signs of ongoing inflammation, but with a signature of a controlled response, lacking homing marker expression and featuring a concomitant increase of Th2-shifted CD4+ T cells and Treg cells. Low versus high threshold reactivity-groups had differential frequencies of intermediate monocytes and myeloid dendritic cells at baseline. Low threshold was associated with increased CD8+ T cells and reduced memory cells (central memory [CM] CD4+ [Th2] T cells, CM CD8+ T cells, Treg). Immune signatures also discriminated patients with preferential skin versus gastrointestinal symptoms, whereby skin signs correlated with increased expression of CCR4, a molecule enabling skin trafficking, on various immune cell types. CONCLUSION: We showed that peripheral immune signatures reflected dynamics of clinical outcome during OFC with peanut. Those immune alterations hold promise as a basis for predictive OFC biomarker discovery to monitor disease outcome and therapy of PA.

EAACI Molecular Allergology User's Guide 2.0.

Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.

α-Gal present on both glycolipids and glycoproteins contributes to immune response in meat-allergic patients.

BACKGROUND: The α-Gal syndrome is associated with the presence of IgE directed to the carbohydrate galactose-α-1,3-galactose (α-Gal) and is characterized by a delayed allergic reaction occurring 2 to 6 hours after ingestion of mammalian meat. On the basis of their slow digestion and processing kinetics, α-Gal-carrying glycolipids have been proposed as the main trigger of the delayed reaction. OBJECTIVE: We analyzed and compared the in vitro allergenicity of α-Gal-carrying glycoproteins and glycolipids from natural food sources. METHODS: Proteins and lipids were extracted from pork kidney (PK), beef, and chicken. Glycolipids were purified from rabbit erythrocytes. The presence of α-Gal and IgE binding of α-Gal-allergic patient sera (n = 39) was assessed by thin-layer chromatography as well as by direct and inhibition enzyme-linked immunosorbent assay. The in vitro allergenicity of glycoproteins and glycolipids from different meat extracts was determined by basophil activation test. Glycoprotein stability was evaluated by simulated gastric and intestinal digestion assays. RESULTS: α-Gal was detected on glycolipids of PK and beef. Patient IgE antibodies recognized α-Gal bound to glycoproteins and glycolipids, although binding to glycoproteins was more potent. Rabbit glycolipids were able to strongly activate patient basophils, whereas lipid extracts from PK and beef were also found to trigger basophil activation, but at a lower capacity compared to the respective protein extracts. Simulated gastric digestion assays of PK showed a high stability of α-Gal-carrying proteins in PK. CONCLUSION: Both α-Gal-carrying glycoproteins and glycolipids are able to strongly activate patient basophils. In PK and beef, α-Gal epitopes seem to be less abundant on glycolipids than on glycoproteins, suggesting a major role of glycoproteins in delayed anaphylaxis upon consumption of these food sources.

Allergenic risk assessment of cowpea and its cross-reactivity with pea and peanut.

BACKGROUND: Novel protein sources can represent a risk for allergic consumers. The aim of this study was to evaluate the allergenicity of cowpea (Vigna unguiculata), an increasingly consumed legume and potential new industrial food ingredient which may put legume-allergic patients at risk. METHODS: Children with allergy to legumes associated to peanut (LP group: n = 13) or without peanut allergy (L group: n = 14) were recruited and sensitization to several legumes including cowpea was assessed by prick tests and detection of specific IgE (sIgE). Cowpea protein extract was analyzed by SDS-PAGE and immunoblotting, IgE-reactive spots were subjected to mass spectrometry. IgE-cross-reactivity between cowpea, pea, and peanut was determined using ELISA inhibition assays. Basophil activation tests were performed to evaluate sensitivity and reactivity of patient basophils toward legumes. RESULTS: Prick tests and sIgE levels to cowpea were positive in 8/14 and 4/13 patients of the L group and in 9/13 and 10/13 patients of the LP group, respectively. Four major IgE-binding proteins were identified as vicilins and seed albumin. Cowpea extract and its vicilin fraction strongly inhibited IgE-binding to pea and peanut extract. Peanut, lentil, and pea were the strongest activators of basophils, followed by cowpea, soybean, mung bean, and lupin. CONCLUSION: A majority of patients with legume allergy were sensitized to cowpea proteins. Four novel allergens were identified in cowpea, among which storage proteins were playing an important role in IgE-cross-reactivity, exposing legume-allergic patients to the risk of clinical cross-reactivity to cowpea and thus adding cowpea to the group of nonpriority legumes that are not subjected to allergen labeling such as chickpea, pea, and lentil.

Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone.

SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here, we compared the neutralizing abilities of sera from 70 unvaccinated COVID-19 patients infected before the emergence of variants of concern (VOCs) and of 16 vaccine breakthrough infection (BTI) cases infected with Gamma or Delta against the ancestral B.1 strain, the Gamma, Delta and Omicron BA.1 VOCs using live virus. We further determined antibody levels against the Nucleocapsid (N) and full Spike proteins, the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the Spike protein. Convalescent sera featured considerable variability in the neutralization of B.1 and in the cross-neutralization of different strains. Their neutralizing capacity moderately correlated with antibody levels against the Spike protein and the RBD. All but one convalescent serum failed to neutralize Omicron BA.1. Overall, convalescent sera from patients with moderate disease had higher antibody levels and displayed a higher neutralizing ability against all strains than patients with mild or severe forms of the disease. The sera from BTI cases fell into one of two categories: half the sera had a high neutralizing activity against the ancestral B.1 strain as well as against the infecting strain, while the other half had no or a very low neutralizing activity against all strains. Although antibody levels against the spike protein and the RBD were lower in BTI sera than in unvaccinated convalescent sera, most neutralizing sera also retained partial neutralizing activity against Omicron BA.1, suggestive of a better cross-neutralization and higher affinity of vaccine-elicited antibodies over virus-induced antibodies. Accordingly, the IC50: antibody level ratios were comparable for BTI and convalescent sera, but remained lower in the neutralizing convalescent sera from patients with moderate disease than in BTI sera. The neutralizing activity of BTI sera was strongly correlated with antibodies against the Spike protein and the RBD. Together, these findings highlight qualitative differences in antibody responses elicited by infection in vaccinated and unvaccinated individuals. They further indicate that breakthrough infection with a pre-Omicron variant boosts immunity and induces cross-neutralizing antibodies against different strains, including Omicron BA.1.

Component-resolved diagnosis using guinea-pig allergens elucidates allergen sensitization profiles in allergy to furry animals.

BACKGROUND: Furry animals are an important source of indoor allergens. Diagnosis of allergy to small pets such as guinea-pigs still relies on animal dander extracts which do not allow to define the primary sensitization source. OBJECTIVE: To identify major guinea-pig allergens and to evaluate their potential as marker allergens for in vitro IgE-diagnosis in comparison with dander extracts. METHODS: A group of patients allergic to guinea-pig (n = 29) and a group of patients allergic to cat and dog (n = 30) were recruited for the study. A panel of four guinea-pig lipocalin allergens was expressed as recombinant proteins in E. coli. Specific IgE were quantified by ImmunoCAP and ELISA. RESULTS: The combination of 4 guinea-pig lipocalin allergens, including 2 new lipocalins, Cav p 1.0201 and Cav p 6.0101, and the previously characterized lipocalins Cav p 2 and Cav p 3, enabled the identification of 90% of all patients allergic to guinea-pig. The vast majority had specific IgE to Cav p 1 (83%). Cav p 6 shares 54% sequence identity with Fel d 4 and Can f 6 and was found to be IgE-cross-reactive with these allergens. In the group of cat- and dog-allergic patients, 73% had also specific IgE to guinea-pig dander. However, only 27% of the cat /dog-allergic patients had specific IgE to any of the non-cross-reactive guinea-pig allergens Cav p 1, Cav p 2 or Cav p 3. The high prevalence of IgE to guinea-pig dander could be explained by IgE-cross-reactivity among serum albumins and certain lipocalins. CONCLUSIONS AND CLINICAL RELEVANCE: The availability of specific allergen markers is essential for the assessment of primary sensitization, especially in polysensitized patients. The proposed panel of guinea-pig allergens Cav p 1, Cav p 2 and Cav p 3 is a first step to component-resolved IgE-diagnosis of allergy to small furry pets.

Carbohydrate epitopes currently recognized as targets for IgE antibodies.

Until recently, glycan epitopes have not been documented by the WHO/IUIS Allergen Nomenclature Sub-Committee. This was in part due to scarce or incomplete information on these oligosaccharides, but also due to the widely held opinion that IgE to these epitopes had little or no relevance to allergic symptoms. Most IgE-binding glycans recognized up to 2008 were considered to be "classical" cross-reactive carbohydrate determinants (CCD) that occur in insects, some helminths and throughout the plant kingdom. Since 2008, the prevailing opinion on lack of clinical relevance of IgE-binding glycans has been subject to a reevaluation. This was because IgE specific for the mammalian disaccharide galactose-alpha-1,3-galactose (alpha-gal) was identified as a cause of delayed anaphylaxis to mammalian meat in the United States, an observation that has been confirmed by allergists in many parts of the world. Several experimental studies have shown that oligosaccharides with one or more terminal alpha-gal epitopes can be attached as a hapten to many different mammalian proteins or lipids. The classical CCDs also behave like haptens since they can be expressed on proteins from multiple species. This is the explanation for extensive in vitro cross-reactivity related to CCDs. Because of these developments, the Allergen Nomenclature Sub-Committee recently decided to include glycans as potentially allergenic epitopes in an adjunct section of its website (www.allergen.org). In this article, the features of the main glycan groups known to be involved in IgE recognition are revisited, and their characteristic structural, functional, and clinical features are discussed.

The basophil activation test differentiates between patients with alpha-gal syndrome and asymptomatic alpha-gal sensitization.

BACKGROUND: Galactose-alpha-1,3-galactose (alpha-gal) syndrome is characterized by the presence of serum specific IgE antibodies to alpha-gal and delayed type I allergic reactions to the carbohydrate alpha-gal after consumption of mammalian (red) meat products and drugs of mammalian origin. Diagnostics currently rely on patient history, skin tests, determination of serum specific IgE antibodies, and oral food or drug challenges. OBJECTIVE: We sought to assess the utility of different basophil parameters (basophil reactivity and sensitivity, the ratio of the percentage of CD63+ basophils induced by the alpha-gal-containing allergen to the percentage of CD63+ basophils after stimulation with anti-FcεRI antibody [%CD63+/anti-FcεRI], and area under the dose-response curve [AUC]) as biomarkers for the clinical outcome of patients with alpha-gal syndrome compared with subjects with asymptomatic alpha-gal sensitization. METHODS: In addition to routine diagnostics, a basophil activation test (Flow CAST) with different concentrations of alpha-gal-containing allergens (eg, commercially available alpha-gal-carrying proteins and pork kidney extracts) was performed in 21 patients with alpha-gal syndrome, 12 alpha-gal-sensitized subjects, and 18 control subjects. RESULTS: Alpha-gal-containing allergens induced strong basophil activation in a dose-dependent manner in patients. Basophil reactivity at distinct allergen concentrations, the %CD63+/anti-FcεRI ratio across most allergen concentrations, the AUC of dose-response curves, and basophil allergen threshold sensitivity (CD-sens) with pork kidney extract were significantly higher in patients with alpha-gal syndrome compared with those in sensitized subjects. All parameters were negative in control subjects. CONCLUSION: The basophil activation test should be considered as an additional diagnostic test before performing time-consuming and potentially risky oral provocation tests. The %CD63+/anti-FcεRI ratio for all allergens and AUCs for pork kidney were the best parameters for distinguishing patients with alpha-gal syndrome from subjects with asymptomatic alpha-gal sensitization.

Role and Mechanism of Galactose-Alpha-1,3-Galactose in the Elicitation of Delayed Anaphylactic Reactions to Red Meat.

PURPOSE OF REVIEW: The alpha-Gal (α-Gal) syndrome is characterized by the presence of IgE antibodies directed at the carbohydrate galactose-alpha-1,3-galactose (α-Gal). In this article, we review the presence of α-Gal in food and non-food sources; we discuss the evolutionary context of the antibody response to α-Gal and highlight immune responses to α-Gal and other carbohydrates. RECENT FINDINGS: IgE antibodies have been associated with delayed allergy to red meat. In addition to food, drugs, and other products of animal origin are increasingly perceived as a risk for patients sensitized to α-Gal. The link between tick bites and anti-α-Gal IgE-antibody production that has been established first by epidemiological studies has now been confirmed in mouse models. The anti-α-Gal immune response is complex and characterized by a unique feature. IgM and IgG antibodies have been found to confer protection against pathogens whereas the IgE-response to α-Gal is detrimental and causes severe reactions upon exposure to mammalian meat and other products.

Diagnosis of Allergy to Mammals and Fish: Cross-Reactive vs. Specific Markers.

PURPOSE OF REVIEW: Allergen extracts are still widely used in allergy diagnosis as they are regarded as sensitive screening tools despite the fact that they may lack some minor allergens. Another drawback of extracts is their low specificity, which is due to the presence of cross-reactive allergens. Progress in allergen identification has disclosed a number of allergenic molecules of homologous sequence and structure which are present in different animal species. This review summarizes recent advances in mammalian and fish allergen identification and focuses on their clinical relevance. RECENT FINDINGS: Serum albumins and parvalbumins are well-known animal panallergens. More recently several members of the lipocalin family were found to be cross-reactive between furry animals whereas in fish, additional allergens, enolase, aldolase and collagen, were found to be important and cross-reactive allergens. New epidemiological studies have analysed the prevalence and clinical relevance of mammalian and fish components. Primary sensitization can be distinguished from cross-sensitization by using marker allergens. Although substantial progress has been made in allergen identification, only few markers are commercially available for routine clinical practice.

Urtica dioica pollen allergy: Clinical, biological, and allergomics analysis.

BACKGROUND: The most emblematic members of Urticaceae at allergic risk level are wall pellitories (Parietaria), whereas nettle (Urtica) pollen is considered as poorly allergenic. No allergen from nettle pollen has yet been characterized, whereas 4 are listed for Parietaria pollen by the International Union of Immunological Societies. Clinical and biological profiles of 2 adult men who developed symptoms against nettle pollen and/or leaves were studied. OBJECTIVE: To characterize the allergic reaction and identify the potential nettle pollen sensitizing allergens. METHODS: IgE-mediated reaction to nettle pollen extract was evaluated by skin prick test, immunoassay, nasal provocation, and basophil activation test. To characterize specific nettle pollen allergens, an allergomic (IgE immunoproteomic) analysis was performed combining 1- and 2-dimensional electrophoresis, IgE immunoblots of nettle pollen extract, identification of allergens by mass spectrometry, and database queries. RESULTS: The results of biological and immunochemical analyses revealed that the allergic rhinitis was due to Urtica dioica pollen in both patients. The allergomic analysis of nettle pollen extract allowed the characterization of 4 basic protein allergens: a thaumatin-like protein (osmotin) with a relative molecular mass of 27 to 29 kDa, a pectinesterase (relative molecular mass, 40 kDa), and 2 other basic proteins with relative molecular masses of 14 to 16 kDa and 43 kDa. There is no or only very weak allergen associations between pellitory and nettle pollen. CONCLUSION: Exposure to nettle pollen can be responsible of allergic symptoms, and several allergens were characterized. Unravelling the allergens of this underestimated allergy might help to improve diagnosis and care for patients, to predict cross-reactivities and design adapted specific immunotherapy.

Allergy to furry animals: New insights, diagnostic approaches, and challenges.

The prevalence of allergy to furry animals has been increasing, and allergy to cats, dogs, or both is considered a major risk factor for the development of asthma and rhinitis. An important step forward in the diagnosis of allergy to furry animals has been made with the introduction of molecular-based allergy diagnostics. A workshop on furry animals was convened to provide an up-to-date assessment of our understanding of (1) the exposure and immune response to the major mammalian allergens, (2) the relationship of these responses (particularly those to specific proteins or components) to symptoms, and (3) the relevance of these specific antibody responses to current or future investigation of patients presenting with allergic diseases. In this review research results discussed at the workshop are presented, including the effect of concomitant exposures from other allergens or microorganisms, the significance of the community prevalence of furry animals, molecular-based allergy diagnostics, and a detailed discussion of cat and dog components.

Male-specific submaxillary gland protein, a lipocalin allergen of the golden hamster, differs from the lipocalin allergens of Siberian and Roborovski dwarf hamsters.

BACKGROUND: An increasing number of asthma cases upon exposure to hamsters and anaphylactic reactions following hamster bites are being reported, but the allergens responsible are still poorly characterized. In the Golden hamster, male-specific submaxillary gland protein (MSP), a lipocalin expressed in a sex- and tissue-specific manner in the submaxillary and lacrimal glands, is secreted in the saliva, tears and urine. The purpose of this study was to determine if MSP is an allergen, to identify IgE-reactive proteins of different hamster species and to analyse potential cross-reactivities. METHODS: Fur extracts were prepared from four hamster species. Hamster-allergic patients were selected based on a history of positive IgE-test to hamster epithelium. The IgE-reactivity of patients' sera was investigated by means of immunoblot and ELISA. IgE-reactive proteins in fur extracts and the submaxillary gland were identified using anti-MSP antibodies, Edman sequencing or mass spectrometry. MSP was purified from Golden hamster and recombinant MSP was expressed in E. coli. RESULTS: Four patients had IgE-antibodies against 20.5-kDa and 24-kDa proteins of Golden hamster fur extract, which were identified as MSP. IgE-reactive MSP-like proteins were detected in European hamster fur extract. Three patient sera showed IgE-reactive bands at 17-21 kDa in Siberian and Roborovski hamster fur extracts. These proteins were identified as two closely related lipocalins. Immunoblot inhibition experiments showed that they are cross-reactive and are different from MSP. CONCLUSION: MSP lipocalin of the Golden hamster was identified as an allergen, and it is different from the cross-reactive lipocalin allergens of Siberian and Roborovski hamsters. Our findings highlight the need for specific tools for the in vitro and in vivo diagnosis of allergy to different hamster species.

Identification and isolation of a Fel d 1-like molecule as a major rabbit allergen.

BACKGROUND: Rabbits are increasingly kept as domestic pets. Several rabbit allergens have been characterized. However, their sequences are still elusive, and none of these molecules are available for diagnosis. OBJECTIVE: We sought to isolate major allergens from the rabbit Oryctolagus cuniculus and to investigate their importance in sensitized patients. METHODS: Proteins were extracted from rabbit hair, and IgE-reactive proteins were purified by using sequential chromatography. Allergens were characterized by means of N-terminal sequencing and mass spectrometry. IgE reactivity to a new allergen was analyzed in sera of 35 patients sensitized to rabbits in a domestic setting. A model of the crystal structure of the isolated proteins was constructed. RESULTS: A new IgE-reactive allergen, Ory c 3, was identified as rabbit lipophilin. The molecule that belongs to the secretoglobin family is a heterodimer of 18 to 19 kDa composed of 2 polypeptide chains, CL2 and AL. CL2 has a predicted N-linked glycosylation site confirmed by using mass spectrometry. Of the 35 patients with rabbit allergy studied, 27 (77%) had IgE to both the glycosylated and deglycosylated Ory c 3 heterodimer. Allergenicity of Ory c 3 was confirmed by using skin prick tests and the basophil activation assay. Modeling of the structure revealed a marked homology to Fel d 1, the major cat allergen. However, no IgE cross-reactivity was detected between Fel d 1 and Ory c 3. CONCLUSION: The rabbit lipophilin heterodimer AL-CL2 has been identified as a major rabbit allergen. After Fel d 1, Ory c 3 is the second mammalian secretoglobin shown to be a major allergen.

Hypoallergenic animals: A promise of hope for allergic patients?

Furry pets are beloved companion animals; horse riding is a popular leisure activity. So-called hypoallergenic animals have gained high interest as sensitization to animal dander and allergy to furry animals are widespread. Allergen immunotherapy to furry animals is still limited, and allergen avoidance in addition to symptomatic pharmaceutical treatment is often the only available option. Patients with an existing allergy to furry animals or with an atopic background are seeking for a hypoallergenic alternative. This review summarizes current knowledge and discusses future strategies.

Recurrent tick bites induce high IgG1 antibody responses to α-Gal in sensitized and non-sensitized forestry employees in Luxembourg.

BACKGROUND: The α-Gal syndrome (AGS) is characterized by the presence of specific IgE-antibodies to the carbohydrate galactose-α-1,3-galactose (α-Gal). Sensitization to α-Gal has been associated with tick bites and individuals exposed to ticks have an elevated risk of sensitization. The aim of this study was to analyze IgG and IgE antibody responses to α-Gal in a high-risk cohort of forestry employees (FE) in Luxembourg. METHODS: Questionnaires and serum samples of FE from Luxembourg (n = 219) were retrospectively analyzed. α-Gal specific IgE was quantified by ImmunoCAP, α-Gal specific IgG and subclasses IgG1-4 were determined by ELISA. Additionally, sera from population-based controls (n = 150) and two groups of food-allergic patients, patients with AGS (n = 45) and fish-allergic patients (n = 22) were assessed for IgG antibody responses to α-Gal and cod extract. RESULTS: Twenty-one percent of FE was sensitized to α-Gal (sIgE ≥ 0.1 kUA/L). Both sensitized and non-sensitized FE exhibited high levels of α-Gal specific IgG, IgG1 and IgG3 compared with controls, indicating a stimulation of IgG responses by recurrent tick bites, independent of the sensitization status. AGS patients had the highest levels of IgG1 and IgG2 antibodies, whereas the profile of fish-allergic patients was similar to the profile of the controls for which anti-α-Gal responses were dominated by IgG2 antibodies. α-Gal sIgG4 levels were either very low or undetectable in all groups. CONCLUSION: Our study provides evidence for a continuous stimulation of α-Gal related immune responses by repeated tick bites, translating into highly elevated levels of IgG1 antibodies directed against α-Gal.