Mite allergens: an overview.

Mite allergens from the Pyroglyphidae family are the most frequent and potent sources of perennial asthma and rhinitis. Since 1988 molecular knowledge has considerably increased and structures and functions have been determined for most of them. Of the 22 denominated allergens, Der p 1 and Der p 2 are major allergens recognized by more than 80% of lgE from Dpt allergic patients in Europe. Der p 4, Der p 5 and Der p 7 appeared to be intermediate allergens. The binding of IgE to groups 3, 6, 8, 9, 10 and 20 is constantly low. Most of the allergens can be identified by amino-acid sequences and the tertiary structure of the major allergens has been solved. Most Dpt mite allergens are proteolytic enzymes: Der p 1 for instance is a cysteine protease. Der p 2 has structural homology with MD-2, a co-receptor of the Toll-like receptor (TLR4) whose ligand is LPS. Knowledge of the mite allergens structure has allowed a better interpretation of cross reactions between allergens from the same family or from more distant families. From a practical point of view molecular epidemiology has allowed a better choice of allergen molecules useful for diagnosis. Finally, new concepts of immunotherapy based on genetically engineered hypoallergenic variants of major allergens, used alone or in combination, can be considered.

[House dust mites allergens]. / Les acariens domestiques et leurs allergènes.

INTRODUCTION: House dust mite allergens from the Pyroglyphidae family are one of the most frequent and potent causes of allergic sensitatisation. Since 1988, molecular knowledge has increased considerably and structures and functions have been determined for most of them. BACKGROUND: Of the 22 defined allergens, the major IgE-binding has been reported for groups 1 and 2 accounting for 40-60% of the anti-house dust mite titres. Der p 1, 2, 4, 5, 7 allergens account for about 80% of the IgE-response. Der p 4, 5, 7, 11, 14, 15 have a prevalence of sensitization of about 10% each. The IgE-binding to groups 3, 8, 10, 20 is low. Most of the allergens can be identified by amino-acid sequences and the tertiary structures of the major allergens have been solved. Most allergens are proteolytic enzymes: Der p1 for instance is a cysteine protease. Der p 2 has structural homology with MD-2, a co-receptor of the Toll-like receptor (TLR4) whose ligand is LPS. Knowledge of the structure of mite allergens has allowed better interpretation of cross-reactions between allergens from the same family or from more distant families. CONCLUSIONS: From a practical point of view: the occurrence of multisensitisation is better explained and molecular epidemiology has allowed a better choice of allergen molecules useful for diagnosis. Finally, new concepts of immunotherapy based on genetically engineered hypoallergenic variants of major allergens, used alone or in combination, may lead to useful therapeutic approach.

[House dust mites and their allergens]. / Les acariens domestiques et leurs allergènes. Biologie et écologie des acariens.

The taxonomy, anatomy, life cycle and ecology of Pyroglyphidae mites and storage mites (Acaridae, Glycyphagidae, B. tropicalis) are described. Pyroglyphidae and storage mites have similar morphologies: they are octopods, with characteristic gnathosoma and sensory hairs. Salivary glands and the mid gut produce most of the allergens excreted, which are enzymatic proteins. Biological cycles and development are similar, although fecundity is superior in storage mites compared to the Pyroglyphides. Relative humidity is the main parameter, which regulates mite development, with a higher degree of temperature and humidity required for storage mites. Bedding is the ecological niche of Pyroglyphidae, which feed on human skin. Moulds and food products are the storage mite biotope from which they spread in the dwelling. Initially considered as rural mites, storage mites are also present in urban dwellings. B. tropicalis, in tropical regions is a true domestic mite. Because of this, it is justified to denominate Pyroglyphidae "house dust mites" and storage mites "domestic mites". In addition to the respiratory allergic symptoms, the storage mites can also cause occupational contact dermatoses.

Molecular allergology in practice: an unusual case of LTP allergy.

The authors describe an unusual case of LTP allergy. A 35 years old patient presented repeated episodes of angiooedema after food intake and complained 10 years ago of contact urticaria and rhinoconjunctivitis when exposed to cannabis leaves and to marijuana smoke. The suspected responsible foods, such as wheat flour in bread, are known to contain LTR Oral syndrome occurred after ingestion of walnuts. Cutaneous tests confirmed immediate responses to several flours and nuts and also to cannabis leaf and flower. A few months later he had similar accidents following peach ingestion and drinking of beer and several wines which all induced positive skin tests. Serological investigations using ImmunoCAP and ISAC microarray confirmed IgE positivity for n Pru p3, r Cor a 8 and n Art v3. It was assumed that sensitization to LTP, the major allergen of cannabis, was responsible of the primary sensitization and induced further LTP food allergies.

Tropomyosin or not tropomyosin, what is the relevant allergen in house dust mite and snail cross allergies?

Since tropomyosin is cross reactive in many arthropods, it was assumed that this highly conserved protein could be responsible for cross reactions in house dust mite (HDM) allergic patients who experienced adverse reactions after crustacean and mollusc ingestion. Here we report two clinical cases where the role of tropomyosin is a matter of debate. In the first case, the clinical history, as well as the results of in vivo and in vitro investigations, are in favour of a shrimp allergy without any snail allergy in a patient sensitized to HDM. In the second, the clinical history and the cutaneous tests are in favour of an allergy to snails without any allergy to shrimps in a patient suffering from HDM allergies. The clinical presentation is different in shrimp and snail allergies. In shrimp allergy, symptoms are mainly urticaria or angio-oedema. In snail allergies, adverse reactions are especially severe asthma. Shrimp tropomyosin is a dominant allergen in crustaceans whereas has a much less prominent role in HDM sensitization. Cross reactivities between HDM and snails have been confirmed by inhibition experiments. However, tropomyosin appears to be a minor allergen or even is not involved in snail allergy. It is necessary to clarify the allergens shared between HDMI and snails. The effects of HDM immunotherapy in snail allergy are questioned. Knowledge of taxonomy can contribute to more precise evaluation of cross reactivities between crustaceans and molluscs.

Rare indoor allergens.

Rare allergens in indoor environment are insufficiently recognized. The sources are diverse: they include animal, namely acaride, insect and mammalian allergens or vegetable allergens. The prevalence of sensitization to rare allergens depends on geographical and climatological characteristics, on people's habits and overall on dwelling specificities. Sensitizations to new rare allergens should be confirmed by documented clinical history, by immunological tests, and by the beneficial effects of avoidance. A review of rare and/or new allergens likely to be present in indoor environment is presented.

[Respiratory allergies: current data]. / Les allergènes respiratoires: données actuelles.

Over the last decade, advances in our knowledge of allergens and in methods for determining their structure have given the clinician a molecular rather than macroscopic view of allergy. The prevalence of sensitization to different allergenic molecules is known for the principal pneumallergens. This knowledge is crucial for understanding the cross reactions between respiratory allergens. The main cross reactions are described here for pollen, mites, roaches, and mammals. In addition, the biological function of a certain number of respiratory allergens are known. Allergens with an enzymatic function, allergens with a transport function, allergens implicated in the regulation of muscle contraction, and allergens participating in the protein defense system have been identified. Potential factors underlying the allergenicity of airborne allergens are discussed: physical properties, structures, biological functions. The diversity of biological functions prohibits retaining a single specific function as a prerequisite for allergenicity; certain major allergens do not have a defined function. No structural form appears to be incompatible with the allergenic potential of a protein found in the environment.

[Asthma from tropical abachi wood]. / L'asthme au bois d'abachi.

We report the case of a 28-year old man suffering from rhinitis and asthma which appeared 8 years after exposure to different woods, especially abachi wood. Serial PEFR monitoring at work and away from work were consistent with occupational asthma. Spirometry showed an airway obstruction, and metacholine inhalation test was positive. Skin prick-tests performed with different woods were only positive to abachi wood extract. The search for specific IgE was positive to abachi wood (4, 98 KU/l, class 3). The diagnosis of occupational asthma caused by exposure to abachi wood was established, the mechanism underlying this asthma was IgE mediated. Despite respiratory protection measures, the patient had persisting symptoms and was laid off. The German service for social cover asked for an expert evaluation: specific nasal and inhalation provocation tests performed by exposure to fine abachi wood dust were positive. This is an observation with a double significance: first, although the mechanisms underlying wood occupational asthma remain largely unknown, an IgE mechanism for abachi wood was demonstrated; second, legislation is different in France and Germany where occupational asthma will only be acknowledged if inhalation tests are positive.

Urticaria and rhinitis to shrubs of Ficus benjamina and breadfruit in a banana-allergic road worker: evidence for a cross-sensitization between Moracea, banana and latex.

BACKGROUND: We report the case of a road worker with a food allergy to banana, who developed urticaria and rhinitis when cutting shrubs of Ficus benjamina and breadfruit. He did not develop an allergy to latex of Hevea brasiliensis. RESULTS: Sensitization to latex of F. benjamina, H. brasiliensis, breadfruit and banana was demonstrated using skin tests and specific IgE measurements. RAST inhibitions procedures showed that specific IgE to breadfruit latex cross-reacted more strongly with latex of H. brasiliensis and banana than with latex of F. benjamina with the same extract. CONCLUSION: Given the wide distribution of Moracea trees in tropical regions, sensitization to latex of H. brasiliensis and banana could be a consequence of sensitization to Moracea members; F. benjamina does not seem to be the only Moracea responsible for cross-allergy with latex and fruit. Consequently, it seems interesting to test other members of the Moracea family in patients sensitized to latex of H. brasiliensis and banana. Sensitization to breadfruit could be a risk factor for sensitization to latex of H. brasiliensis.

[Physiopathology of hay fever]. / Physiopathologie de la pollinose.

Pollinosis is a model physio-pathology for IgE-dependent diseases. Rhinitis and conjunctivitis are the parent symptoms, with asthma a non-exceptional complication. The mechanisms are linked to an immuno-allergic inflammation; the observed differences are due to specific anatomo-physiologies of the sensitive cells. The pollen allergens are collected by the CPA and expressed after cleavage into peptides, at the surface of the CPA in association with class II HLA molecules. T-lymphocytes recognise the complex HLA-peptide molecules. Type Th2 lymphocytes produce the cytokines that the necessary for the synthesis of IgE (IL4, IL13...). At the stage of silent clinical sensitivity the precocious and delayed effector stages of immediate hypersensitivity follow. The precocious stage corresponds with degranulation of cells that express Fc epsilon R1, for release of vaso-active and lipid mediators that produce the immediate symptoms of pollinosis. The delayed phase corresponds with a flood of eosinophils, which release their toxic proteins proteins and also take part in oedema and nasal obstruction. Mucosal innervation, neurotransmitters and neuromediators also intervene in the modulation of symptoms.

[Mites and their allergens: identification and extermination methods]. / Les acariens et leurs allergènes: identification et mesures d'éviction.

Mite allergens are the main allergens in indoor environment. Using different means of assessing exposure to house dust mites (Acarex-test, major allergen (Der p 1 + Der f 1, Der p 2 + Der f 2), content measured by ELISA) has allowed better identification of mite reservoirs and allergens in patients' homes. House dust mite control measures are based on the knowledge of factors contributing to mite development, especially indoor relative humidity. Mite allergen avoidance strategies include 3 different methods: avoidance of mite producing allergens, elimination of mite reservoirs, especially textile reservoirs, dwellings designed so as to inhibit mite proliferation. Only controlled trials can estimate patients' compliance with proposed avoidance measures. Avoidance protocols should be adjusted to each individual by medical indoor environment counselors in order to optimize mite allergen reduction.

[Respiratory allergies and household allergenic environment]. / Allergies respiratoires et environnement allergénique domestique.

Based on immunoassay techniques used to identify and quantify major indoor allergens, epidemiological studies have demonstrated that level of exposure depends on the geographical situation (climate, urbanization) and that there is a relationship between exposure and sensitization of predisposed patients. Most of the major mite allergens are proteases. For mammals and cockroaches, the major allergens belong to the retinal protein binding group. Determination of the airborne characteristics of the major indoor allergens is helpful in better understanding the pathophysiology of asthma. In the future, more precise diagnosis and more efficient immunotherapy will be possible through the development of recombinant allergens. The efficacy of allergen avoidance in allergic asthma has been demonstrated in several studies. Thus the respective role of different household allergens should lead to improved diagnosis and treatment of allergic diseases.

[Exploration of respiratory allergies and prevention]. / Exploration des allergies respiratoires et prévention.

Respiratory allergies are found in more than 50% of the asthmatics. Allergen sources and their secondary reservoirs are better known. The different methods of exploration of allergic asthma consist of clinical history, skin tests, and in vitro tests particularly measurement of specific serum IgE. Specific challenge tests are realized with nebulized allergenic extracts as well as in the realistic manner with substances in occupational environment. It is equally important to evaluate the allergenic environment, especially by simple but informative techniques such as the Acarex test for mites. The eviction methods are the same for primary prevention (to prevent sensitization) as well as for the secondary prevention (to reduce the disease exacerbation in the patients already sensitized). The eviction methods mainly concern the allergens of mites, domestic animals, cockroaches and the molds.

[Occupational asthma caused by a coloring reagent]. / Asthme et rhinite professionnels à un colorant réactif.

A case of occupational asthma associated with rhinitis and conjunctivitis occurred in a patient working in a textile factory and exposed to different coloring reagents is reported. Symptoms appeared in phases correlated with changes in the use of the coloring reagents. Prick tests were carried out with the different coloring reagents and were positive for the yellow color. The test was followed by a clear increase in bronchial hyperreactivity to methacholine. Some individual preventive measures, such as wearing a face mask, led to reduction then disappearence of the symptoms.

Genetics and specific immune response in allergy to birch pollen and food: evidence of a strong, positive association between atopy and the HLA class II allele HLA-DR7.

BACKGROUND: In some geographic areas birch pollen represents the most prominent cause for airborne allergic diseases. Up to 70% of patients allergic to birch pollen are hypersensitive to fruits, especially apples. Associations have been found, in some instances, with a sensitivity to aeroallergens and HLA class II genes. OBJECTIVES: We investigated whether susceptibility or resistance to birch pollen allergy with and without food allergy was associated with HLA class II genes. METHODS: Blood samples were obtained from 2 groups of unrelated European-born white adults: 42 atopic patients (31 of them with asthma) and 42 healthy control subjects with no personal or familial history of asthma or atopy. Their antibody responses to birch pollen, apples, grass, and weed pollens were evaluated by skin tests, RASTs, and immunoprints. Genomic DNA was extracted from PBLs. The exons of DQA1, DQB1, DRB1, and DPB1 genes were selectively amplified by using the PCR method. Genotyping was carried out by digestion of the amplified DNA products with allele-specific endonucleases (PCR-RFLP), which recognize allelic variations in the polymorphic exon. RESULTS: We found no significant differences in the frequency of DPB1 alleles between patients and control subjects. HLA class II DR4 and/or DR7 alleles were present in 42.6% of the patients and in only 2.4% of the healthy subjects. These results confirm a previous study of a group of polysensitized atopic patients, which showed that DR4 and DR7 alleles were rare in healthy control subjects and frequently observed in atopic subjects with or without concomitant asthma. CONCLUSION: We conclude that the allele HLA-DR7 is significantly involved in the presentation of apple and pollen allergens. However, we suggest that this susceptibility is more related to atopy than to specific responses to allergens.

[Occupational asthma]. / Asthmes professionnels.

Occupational asthma is specifically induced by repeated exposure to substances in the work place. Diagnosis requires using the results of numerous tests, and a challenge test is the most appropriate to establish the diagnosis of occupational asthma due to chemical agents. Agents responsible for occupational asthma may be of animal or vegetable origin, or may be chemical agents. The pathophysiological mechanisms of occupational asthma are not well known. It is probable that immunologic mechanisms play an important role, in particular in occupational asthma due to glycoproteins. An important feature of occupational asthma is the relationship to chemical substances, for which the mechanisms are often still hypothetical. From the legal viewpoint, a recent law holds the promise of better compensation for those who are afflicted.