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Trifonova D, Curin M, Riabova K, Karsonova A, Keller W, Grönlund H, Käck U, Konradsen JR, van Hage M, Karaulov A, Valenta R. Allergenic Activity of Individual Cat Allergen Molecules. Int J Mol Sci 2023; 24:16729. [PMID: 38069052 PMCID: PMC10706119 DOI: 10.3390/ijms242316729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 11/03/2023] [Accepted: 11/06/2023] [Indexed: 12/18/2023] Open
Abstract
More than 10% of the world's population suffers from an immunoglobulin E (IgE)-mediated allergy to cats which is accompanied mainly by respiratory symptoms such as rhinitis and asthma. Several cat allergen molecules have been identified, but their allergenic activity has not been investigated in depth. Purified cat allergen molecules (Fel d 1, Fel d 2, Fel d 3, Fel d 4, Fel d 6, Fel d 7 and Fel d 8) were characterized via mass spectrometry and circular dichroism spectroscopy regarding their molecular mass and fold, respectively. Cat-allergen-specific IgE levels were quantified via ImmunoCAP measurements in IgE-sensitized subjects with (n = 37) and without (n = 20) respiratory symptoms related to cat exposure. The allergenic activity of the cat allergens was investigated by loading patients' IgE onto rat basophils expressing the human FcεRI receptor and studying the ability of different allergen concentrations to induce β-hexosaminidase release. Purified and folded cat allergens with correct masses were obtained. Cat-allergen-specific IgE levels were much higher in patients with a respiratory allergy than in patients without a respiratory allergy. Fel d 1, Fel d 2, Fel d 4 and Fel d 7 bound the highest levels of specific IgE and already-induced basophil degranulation at hundred-fold-lower concentrations than the other allergens. Fel d 1, Fel d 4 and Fel d 7 were recognized by more than 65% of patients with a respiratory allergy, whereas Fel d 2 was recognized by only 30%. Therefore, in addition to the major cat allergen Fel d 1, Fel d 4 and Fel d 7 should also be considered to be important allergens for the diagnosis and specific immunotherapy of cat allergy.
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Affiliation(s)
- Daria Trifonova
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria; (D.T.)
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, 119991 Moscow, Russia (A.K.)
| | - Mirela Curin
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria; (D.T.)
| | - Ksenja Riabova
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, 119991 Moscow, Russia (A.K.)
| | - Antonina Karsonova
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, 119991 Moscow, Russia (A.K.)
| | - Walter Keller
- Institute of Molecular Biosciences, BioTechMed Graz, University of Graz, 8010 Graz, Austria;
| | - Hans Grönlund
- Therapeutic Immune Design Unit, Department of Clinical Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden;
| | - Ulrika Käck
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, 11883 Stockholm, Sweden;
| | - Jon R. Konradsen
- Pediatric Allergy and Pulmonology, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, 17164 Stockholm, Sweden
- Department of Women’s and Children’s Health, Karolinska Institutet, 17177 Stockholm, Sweden
| | - Marianne van Hage
- Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet and University Hospital, 17177 Stockholm, Sweden;
| | - Alexander Karaulov
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, 119991 Moscow, Russia (A.K.)
| | - Rudolf Valenta
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria; (D.T.)
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, 119991 Moscow, Russia (A.K.)
- Karl Landsteiner University for Healthcare Sciences, 3500 Krems, Austria
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Popescu FD, Ganea CS, Panaitescu C, Vieru M. Molecular diagnosis in cat allergy. World J Methodol 2021; 11:46-60. [PMID: 34026578 PMCID: PMC8127422 DOI: 10.5662/wjm.v11.i3.46] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 02/22/2021] [Accepted: 05/10/2021] [Indexed: 02/06/2023] Open
Abstract
Domestic cats represent one of the most common sources of indoor allergens. All over the world, many households own cats, whose allergens are persistent and widespread. Cat allergy itself is frequent, and its symptoms vary from rhinoconjunctivitis to life-threatening asthma. In vitro diagnosis using precision medicine allergy immunoassays is important because natural cat dander extracts may differ in quality and quantity of some of the individual allergen components and other molecules. In the component-resolved diagnosis of cat allergy, singleplex and multiplex specific immunoglobulin (Ig) E assays include use of the cat-specific major allergen, secretoglobin Fel d 1 (as a species-specific molecule), other allergen components (such as lipocalins Fel d 4, cross-reacting with other animal similar molecules, and Fel d 7, present in small quantities in natural extracts), and serum albumin Fel d 2 (related to the cat-pork syndrome). IgA Fel d 5 and IgM Fel d 6 are not available as allergen components in the current commercial IgE immunoassays, but they may impair the in vitro diagnostic evaluation of cat allergy because galactose-α1,3-galactose is an IgE-binding epitope of these native feline allergens. The benefits of molecular-based cat allergy diagnosis are continually evaluated, as the role of recombinant allergen components already known is detailed and new other molecules of interest may be discovered in the future.
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Affiliation(s)
- Florin-Dan Popescu
- Department of Allergology and Clinical Immunology, “Nicolae Malaxa” Clinical Hospital, Bucharest 022441, Romania
- Department of Allergology, “Carol Davila” University of Medicine and Pharmacy, Bucharest 022441, Romania
| | - Carmen Saviana Ganea
- Department of Allergology and Clinical Immunology, “Nicolae Malaxa” Clinical Hospital, Bucharest 022441, Romania
| | - Carmen Panaitescu
- Department III Functional Sciences, Physiology Discipline, “Victor Babes” University of Medicine and Pharmacy, Timișoara 300041, Romania
- Center for Gene and Cell Therapies in Cancer Treatment OncoGen-SCJUPB Timisoara, Timișoara 300041, Romania
| | - Mariana Vieru
- Department of Allergology and Clinical Immunology, “Nicolae Malaxa” Clinical Hospital, Bucharest 022441, Romania
- Department of Allergology, “Carol Davila” University of Medicine and Pharmacy, Bucharest 022441, Romania
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Caraballo L, Valenta R, Puerta L, Pomés A, Zakzuk J, Fernandez-Caldas E, Acevedo N, Sanchez-Borges M, Ansotegui I, Zhang L, van Hage M, Abel-Fernández E, Karla Arruda L, Vrtala S, Curin M, Gronlund H, Karsonova A, Kilimajer J, Riabova K, Trifonova D, Karaulov A. The allergenic activity and clinical impact of individual IgE-antibody binding molecules from indoor allergen sources. World Allergy Organ J 2020; 13:100118. [PMID: 32373267 PMCID: PMC7195550 DOI: 10.1016/j.waojou.2020.100118] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 03/27/2020] [Accepted: 03/30/2020] [Indexed: 02/07/2023] Open
Abstract
A large number of allergens have been discovered but we know little about their potential to induce inflammation (allergenic activity) and symptoms. Nowadays, the clinical importance of allergens is determined by the frequency and intensity of their IgE antibody binding (allergenicity). This is a rather limited parameter considering the development of experimental allergology in the last 20 years and the criteria that support personalized medicine. Now it is known that some allergens, in addition to their IgE antibody binding properties, can induce inflammation through non IgE mediated pathways, which can increase their allergenic activity. There are several ways to evaluate the allergenic activity, among them the provocation tests, the demonstration of non-IgE mediated pathways of inflammation, case control studies of IgE-binding frequencies, and animal models of respiratory allergy. In this review we have explored the current status of basic and clinical research on allergenic activity of indoor allergens and confirm that, for most of them, this important property has not been investigated. However, during recent years important advances have been made in the field, and we conclude that for at least the following, allergenic activity has been demonstrated: Der p 1, Der p 2, Der p 5 and Blo t 5 from HDMs; Per a 10 from P. americana; Asp f 1, Asp f 2, Asp f 3, Asp f 4 and Asp f 6 from A. fumigatus; Mala s 8 and Mala s 13 from M. sympodialis; Alt a 1 from A. alternata; Pen c 13 from P. chrysogenum; Fel d 1 from cats; Can f 1, Can f 2, Can f 3, Can f 4 and Can f 5 from dogs; Mus m 1 from mice and Bos d 2 from cows. Defining the allergenic activity of other indoor IgE antibody binding molecules is necessary for a precision-medicine-oriented management of allergic diseases.
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Affiliation(s)
- Luis Caraballo
- Institute for Immunological Research, University of Cartagena, Cartagena, Colombia
- Corresponding author. Institute for Immunological Research, University of Cartagena, Cartagena de Indias, Colombia.
| | - Rudolf Valenta
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- NRC Institute of Immunology FMBA of Russia, Moscow, Russian Federation
- Department of Clinical Immunology and Allergy, Laboratory of Immunopathology, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Leonardo Puerta
- Institute for Immunological Research, University of Cartagena, Cartagena, Colombia
| | - Anna Pomés
- Indoor Biotechnologies, Inc. Charlottesville, VA, USA
| | - Josefina Zakzuk
- Institute for Immunological Research, University of Cartagena, Cartagena, Colombia
| | | | - Nathalie Acevedo
- Institute for Immunological Research, University of Cartagena, Cartagena, Colombia
| | - Mario Sanchez-Borges
- Allergy and Clinical Immunology Department, Centro Médico Docente La Trinidad, Caracas, Venezuela
| | - Ignacio Ansotegui
- Department of Allergy & Immunology Hospital Quironsalud Bizkaia, Bilbao, Spain
| | - Luo Zhang
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
| | - Marianne van Hage
- Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Eva Abel-Fernández
- Inmunotek, Madrid, Spain and University of South Florida College of Medicine, Tampa, USA
| | - L. Karla Arruda
- Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Susanne Vrtala
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Mirela Curin
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Hans Gronlund
- Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
| | - Antonina Karsonova
- Department of Clinical Immunology and Allergy, Laboratory of Immunopathology, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Jonathan Kilimajer
- Inmunotek, Madrid, Spain and University of South Florida College of Medicine, Tampa, USA
| | - Ksenja Riabova
- Department of Clinical Immunology and Allergy, Laboratory of Immunopathology, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Daria Trifonova
- Department of Clinical Immunology and Allergy, Laboratory of Immunopathology, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Alexander Karaulov
- Department of Clinical Immunology and Allergy, Laboratory of Immunopathology, Sechenov First Moscow State Medical University, Moscow, Russia
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Linhart B, Freidl R, Elisyutina O, Khaitov M, Karaulov A, Valenta R. Molecular Approaches for Diagnosis, Therapy and Prevention of Cow´s Milk Allergy. Nutrients 2019; 11:E1492. [PMID: 31261965 PMCID: PMC6683018 DOI: 10.3390/nu11071492] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Revised: 06/24/2019] [Accepted: 06/25/2019] [Indexed: 12/12/2022] Open
Abstract
Cow´s milk is one of the most important and basic nutrients introduced early in life in our diet but can induce IgE-associated allergy. IgE-associated allergy to cow´s milk can cause severe allergic manifestations in the gut, skin and even in the respiratory tract and may lead to life-threatening anaphylactic shock due to the stability of certain cow´s milk allergens. Here, we provide an overview about the allergen molecules in cow´s milk and the advantages of the molecular diagnosis of IgE sensitization to cow´s milk by serology. In addition, we review current strategies for prevention and treatment of cow´s milk allergy and discuss how they could be improved in the future by innovative molecular approaches that are based on defined recombinant allergens, recombinant hypoallergenic allergen derivatives and synthetic peptides.
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Affiliation(s)
- Birgit Linhart
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, 1090 Vienna, Austria.
| | - Raphaela Freidl
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, 1090 Vienna, Austria
| | - Olga Elisyutina
- NRC Institute of Immunology FMBA of Russia, 115478, Moscow, Russia
| | - Musa Khaitov
- NRC Institute of Immunology FMBA of Russia, 115478, Moscow, Russia
| | - Alexander Karaulov
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
| | - Rudolf Valenta
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, 1090 Vienna, Austria
- NRC Institute of Immunology FMBA of Russia, 115478, Moscow, Russia
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
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Wilson JM, Platts-Mills TAE. Meat allergy and allergens. Mol Immunol 2018; 100:107-112. [PMID: 29685461 DOI: 10.1016/j.molimm.2018.03.018] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Revised: 03/19/2018] [Accepted: 03/20/2018] [Indexed: 12/11/2022]
Abstract
IgE-mediated hypersensitivity to ingested animal products, including both mammalian and avian sources, is increasingly appreciated as an important form of food allergy. Traditionally described largely in children, it is now clear that allergy to meat (and animal viscera) impacts both children and adults and represents a heterogeneous group of allergic disorders with multiple distinct syndromes. The recognition of entities such as pork-cat syndrome and delayed anaphylaxis to red meat, i.e- the α-Gal syndrome, have shed light on fundamental, and in some cases newly appreciated, features of allergic disease. These include insights into routes of exposure and mechanisms of sensitization, as well as the realization that IgE-mediated reactions can be delayed by several hours. Here we review mammalian and avian meat allergy with an emphasis on the molecular allergens and pathways that contribute to disease, as well as the role of in vitro IgE testing in diagnosis and management.
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Affiliation(s)
- Jeffrey M Wilson
- Division of Allergy & Immunology, University of Virginia, Charlottesville, VA, USA
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Allergy to pets and new allergies to uncommon pets. Allergol Select 2017; 1:214-221. [PMID: 30402618 PMCID: PMC6040002 DOI: 10.5414/alx01842e] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Accepted: 02/22/2016] [Indexed: 12/16/2022] Open
Abstract
Abstract. Animal dander is an important source of respiratory allergens, and sensitization to allergens from cat and/or dog during childhood represents a risk factor for the development of asthma and rhinitis later in life. The identification and characterization of allergenic components is crucial to improve diagnosis and therapy in patients with allergy to pets. Allergens from furry animals belong to a restricted number of protein families, a large majority are lipocalins or albumins, some are secretoglobins or latherins. Animal dander contains cross-reactive molecules and current efforts aim at defining species-specific allergens that have a high diagnostic sensitivity. Component-resolved diagnosis allows to discriminate genuine sensitization from cross-sensitization. This review contains a detailed description of allergenic components of cat, dog, horse, and small mammalian pets. Sensitizations to exotic pets, a newly emerging issue, are also discussed.
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Gonzalez-Quintela A, Dam Laursen AS, Vidal C, Skaaby T, Gude F, Linneberg A. IgE antibodies to alpha-gal in the general adult population: relationship with tick bites, atopy, and cat ownership. Clin Exp Allergy 2015; 44:1061-8. [PMID: 24750173 DOI: 10.1111/cea.12326] [Citation(s) in RCA: 97] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Revised: 03/06/2014] [Accepted: 03/17/2014] [Indexed: 01/04/2023]
Abstract
BACKGROUND The carbohydrate alpha-gal epitope is present in many animal proteins, including those of red meat and animal immunoglobulins, such as cat IgA. Systemic anaphylaxis to the alpha-gal epitope has recently been described. OBJECTIVE To investigate and compare the prevalence of alpha-gal-specific (s)IgE and its associated factors in the general adult population from two separated (Northern and Southern) European regions (Denmark and Spain, respectively). METHODS Cross-sectional study of 2297 and 444 randomly selected adults from 11 municipalities in Denmark and one in Spain. Alpha-gal sIgE was assessed by ImmunoCAP to bovine thyroglobulin. Additional assessments included a panel of skin prick test (SPT) to common aeroallergens and epidemiological factors, including the history of tick bites in the Danish series. RESULTS The prevalence of positive (≥ 0.1 kUA /L) sIgE to alpha-gal was 5.5% and 8.1% in the Danish and Spanish series, respectively. The prevalence of sIgE ≥ 0.35 kUA /L was 1.8% and 2.2% in Denmark and Spain, respectively. Alpha-gal sIgE positivity was associated with pet ownership in both series and, particularly, cat ownership (data available in the Danish series). Alpha-gal sIgE positivity was associated with atopy (SPT positivity) in both series, although it was not associated with SPT positivity to cat or dog dander. Alpha-gal sIgE positivity was strongly associated with a history of tick bites. CONCLUSIONS AND CLINICAL RELEVANCE The prevalence of alpha-gal sIgE antibodies in these general adult European populations is similarly low. The presence of alpha-gal sIgE antibodies is associated with a history of tick bites, atopy, and cat ownership.
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Lambert C, Sarrat A, Bienvenu F, Brabant S, Nicaise-Roland P, Alyanakian MA, Apoil PA, Capron C, Couderc R, Evrard B, Jaby D, Hémont C, Lainé C, Lelong M, Mariotte D, Martinet J, Rénier G, Sainte-Laudy J, Tabary T, Treiner E, Uring-Lambert B, Vigneron C, Vivinus M, Witthuhn F, Vitte J. The importance of EN ISO 15189 accreditation of allergen-specific IgE determination for reliable in vitro allergy diagnosis. Allergy 2015; 70:180-6. [PMID: 25394543 DOI: 10.1111/all.12546] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/09/2014] [Indexed: 01/05/2023]
Abstract
BACKGROUND Allergen-specific serum immunoglobulin E detection and quantification have become an important step in allergy diagnosis and follow-up. In line with the current trend of laboratory test accreditation to international standards, we set out to design and assess an accreditation procedure for allergen-specific serum IgE. METHODS Method validation according to the accreditation procedure under the EN ISO 15189 standard was carried out for allergen-specific immunoglobulin E determination using the fluoroimmunoenzymatic method ImmunoCAP(®) (ThermoFisher). Data were produced by 25 hospital laboratories in France. A total of 29 allergen specificities including mixes, extracts, and molecular allergens were assayed. Allergen-specific serum immunoglobulin E concentrations ranged from 0.1 to 100 kUA /l. RESULTS Repeatability, reproducibility, and accuracy results fulfilled method validation criteria for automated laboratory tests and proved similar irrespective of the allergen specificity, allergen-specific serum immunoglobulin E concentration, or individual laboratory. CONCLUSION Allergen-specific serum immunoglobulin E determination with the fluoroimmunoenzymatic method ImmunoCAP(®) is a highly repeatable, reproducible, and accurate method which may be considered as a single analyte assay in view of the EN ISO 15189 accreditation procedure.
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Affiliation(s)
- C. Lambert
- Laboratoire d'Immunologie; Pôle de Biologie-Pathologie; CHU St Etienne; Saint-Etienne France
| | - A. Sarrat
- Laboratoire Immunologie-Immunogénétique; Hôpital Pellegrin; CHU Bordeaux; Bordeaux France
| | - F. Bienvenu
- Laboratoire d'Immunologie; CH Lyon-Sud; CHU Lyon; Hospices Civils de Lyon; Pierre-Bénite France
| | - S. Brabant
- Laboratoire d'Immunologie; CHRU Lille; Lille France
| | - P. Nicaise-Roland
- UF d'Immunologie Autoimmunité et Hypersensibilités; Hôpital Bichat Claude Bernard, AP-HP; Paris France
| | - M.-A. Alyanakian
- Laboratoire d'Immunologie Biologique; Hôpital Universitaire Necker Enfants-Malades, AP-HP; Paris France
| | - P.-A. Apoil
- Laboratoire d'Immunologie; Pôle de Biologie; Hôpital de Rangueil; CHU Toulouse; Toulouse France
| | - C. Capron
- Laboratoire d'Hématologie Immunologie; Hôpital Ambroise-Paré; Boulogne Billancourt; France
| | - R. Couderc
- Service de Biochimie et Département d'Immunologie; Hôpital Armand Trousseau; Groupe Hospitalier HUEP, AP-HP; Paris France
| | - B. Evrard
- Laboratoire d'Immunologie CHU Clermont-Ferrand; Clermont-Ferrand France
| | - D. Jaby
- Laboratoire de Biochimie Immunologie Hôpital Delafontaine; CH Saint-Denis; Saint-Denis France
| | - C. Hémont
- Laboratoire d'Immunologie; CHU Nantes; Nantes France
| | - C. Lainé
- Laboratoire Immunologie Cellulaire - Allergologie; Hôpital Pontchaillou; CHU Rennes; Rennes France
| | - M. Lelong
- Laboratoire de Biochimie; CH Le Mans; Le Mans France
| | - D. Mariotte
- Laboratoire d'Immunologie et Immunopathologie; CHU Clemenceau; Caen France
| | - J. Martinet
- Department of Immunology; Rouen University Hospital; Rouen France
| | - G. Rénier
- Laboratoire d'Immunologie et d'Allergologie; CHU Angers; Angers France
| | - J. Sainte-Laudy
- Laboratoire d'immunologie; Hôpital Dupuytren; CHU Limoges; Limoges France
| | - T. Tabary
- Laboratoire d'Immunologie; Hôpital Robert Debré; CHU Reims; Reims France
| | - E. Treiner
- Laboratoire d'Immunologie; Hôpital Sud; CHU Amiens; Amiens France
| | - B. Uring-Lambert
- Laboratoire d'Immunologie; NHC; CHU Strasbourg; Strasbourg France
| | - C. Vigneron
- Laboratoire d'Immunologie; Hôpital Bretonneau; CHRU Tours; Tours France
| | - M. Vivinus
- Laboratoire d'Immunologie; Pôle de Biologie; Hôpital l'Archet 1; CHU Nice; Nice France
| | - F. Witthuhn
- Service Immunologie et Inflammation; Pôle Biologie Santé; CHU Poitiers; Poitiers France
| | - J. Vitte
- Laboratoire d'Immunologie; Assistance Publique Hôpitaux de Marseille; Marseille France
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Abstract
PURPOSE OF REVIEW A novel form of anaphylaxis has been described that is due to IgE antibody (Ab) directed against a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal). Ongoing work regarding the cause and distribution of this IgE response is reviewed. RECENT FINDINGS Our recent work has identified a novel IgE Ab response that has been associated with two distinct forms of anaphylaxis: immediate-onset anaphylaxis during first exposure to intravenous cetuximab and delayed-onset anaphylaxis 3-6 h after ingestion of mammalian food products (e.g. beef and pork). Further studies strongly suggested that tick bites were a cause, if not the only significant cause, of IgE Ab responses to alpha-gal in the United States and internationally. SUMMARY Large numbers of patients with IgE Ab to alpha-gal continue to be identified in the USA and globally. Clinicians should be aware of this IgE response as the reactions often appear to be idiopathic because of the significant delay between eating mammalian meat and the appearance of symptoms.
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Nilsson OB, van Hage M, Grönlund H. Mammalian-derived respiratory allergens - implications for diagnosis and therapy of individuals allergic to furry animals. Methods 2013; 66:86-95. [PMID: 24041755 DOI: 10.1016/j.ymeth.2013.09.002] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2012] [Revised: 08/07/2013] [Accepted: 09/02/2013] [Indexed: 02/08/2023] Open
Abstract
Furry animals cause respiratory allergies in a significant proportion of the population. A majority of all mammalian allergens are spread as airborne particles, and several have been detected in environments where furry animals are not normally kept. The repertoire of allergens from each source belongs to a restricted number of allergen families. Classification of allergen families is particularly important for the characterization of allergenicity and cross-reactivity of allergens. In fact, major mammalian allergens are taken from only three protein families, i.e. the secretoglobin, lipocalin and kallikrein families. In particular, the lipocalin superfamily harbours major allergens in all important mammalian allergen sources, and cross-reactivity between lipocalin allergens may explain cross-species sensitization between mammals. The identification of single allergen components is of importance to improve diagnosis and therapy of allergic patients using component-resolved diagnostics and allergen-specific immunotherapy (ASIT) respectively. Major disadvantages with crude allergen extracts for these applications emphasize the benefits of careful characterization of individual allergens. Furthermore, detailed knowledge of the characteristics of an allergen is crucial to formulate attenuated allergy vaccines, e.g. hypoallergens. The diverse repertoires of individual allergens from different mammalian species influence the diagnostic potential and clinical efficacy of ASIT to furry animals. As such, detailed knowledge of individual allergens is essential for adequate clinical evaluation. This review compiles current knowledge of the allergen families of mammalian species, and discusses how this information may be used for improved diagnosis and therapy of individuals allergic to mammals.
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Affiliation(s)
- Ola B Nilsson
- Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet, Stockholm, Sweden; Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
| | - Marianne van Hage
- Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet, Stockholm, Sweden
| | - Hans Grönlund
- Department of Clinical Neuroscience, Therapeutic Immune Design Unit, Karolinska Institutet, Stockholm, Sweden.
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Abstract
Food allergy is an emerging epidemic in the United States and the Western world. The determination of factors that make certain foods allergenic is still not clearly understood. Only a tiny fraction of thousands of proteins and other molecules is responsible for inducing food allergy. In this review, the authors present 3 examples of food allergies with disparate clinical presentations: peanut, soy, and mammalian meat. The potential relationships between allergen structure and function, emphasizing the importance of cross-reactive determinants, immunoglobulin E antibodies to the oligosaccharides, and the immune responses induced in humans are discussed.
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Affiliation(s)
- Madhan Masilamani
- Division of Allergy and Immunology, Department of Pediatrics, The Jaffe Food Allergy Institute, Mount Sinai School of Medicine, Anbg 17-40, One Gustave L Levy Place, New York, NY 10029, USA
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Impaired allergy diagnostics among parasite-infected patients caused by IgE antibodies to the carbohydrate epitope galactose-α 1,3-galactose. J Allergy Clin Immunol 2011; 127:1024-8. [PMID: 21376382 DOI: 10.1016/j.jaci.2011.01.033] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2010] [Revised: 01/12/2011] [Accepted: 01/13/2011] [Indexed: 12/18/2022]
Abstract
BACKGROUND The carbohydrate epitope galactose-α 1,3-galactose (α-Gal) is abundantly expressed on nonprimate mammalian proteins. We have recently shown that α-Gal is responsible for the IgE binding to cat IgA, a newly identified cat allergen (Fel d 5). OBJECTIVE We sought to investigate the diagnostic relevance of IgE antibodies to Fel d 5 and α-Gal among parasite-infected patients from central Africa without cat allergy compared with patients with cat allergy from the same region. METHODS Sera from 47 parasite-infected patients and 31 patients with cat allergy were analyzed for total IgE and IgE antibodies against cat dander extract (CDE) by using the ImmunoCAP system. Inhibition assay was performed with α-Gal on solid phase-bound CDE. The presence of IgE specific for the major cat allergen Fel d 1, Fel d 5, and α-Gal was analyzed by means of ELISA. RESULTS Among the 47 parasite-infected patients, 85% had IgE antibodies against α-Gal (OD; median, 0.175; range, 0.102-1.466) and 66% against Fel d 5 (OD; median, 0.13; range, 0.103-1.285). Twenty-four of the parasite-infected patients were sensitized to CDE, and 21 of them had IgE antibodies to Fel d 5 and α-Gal. There was no correlation between IgE levels to CDE and rFel d 1 among the parasite-infected patients but a strong correlation between CDE and Fel d 5 and α-Gal (P < .001). Among the group with cat allergy, only 5 patients had IgE to α-Gal, and nearly 75% (n = 23) had IgE to rFel d 1 (median, 7.07 kU(A)/L; range, 0.51-148.5 kU(A)/L). In contrast, among the patients with cat allergy, there was a correlation between IgE levels to CDE and rFel d 1 (P < .05) but no correlation between CDE and Fel d 5 and α-Gal. CONCLUSION IgE to α-Gal causes impaired allergy diagnostics in parasite-infected patients. Screening for IgE to rFel d 1 and other allergens without carbohydrates might identify patients with true cat sensitization/allergy in parasite-infested areas.
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Grönlund H, Adédoyin J, Commins SP, Platts-Mills TAE, van Hage M. The carbohydrate galactose-alpha-1,3-galactose is a major IgE-binding epitope on cat IgA. J Allergy Clin Immunol 2009; 123:1189-91. [PMID: 19362358 DOI: 10.1016/j.jaci.2009.03.011] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2008] [Revised: 03/03/2009] [Accepted: 03/05/2009] [Indexed: 12/23/2022]
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Adédoyin J, Grönlund H, Oman H, Johansson SGO, van Hage M. Cat IgA, representative of new carbohydrate cross-reactive allergens. J Allergy Clin Immunol 2007; 119:640-5. [PMID: 17336613 DOI: 10.1016/j.jaci.2006.11.637] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2006] [Revised: 11/17/2006] [Accepted: 11/17/2006] [Indexed: 11/16/2022]
Abstract
BACKGROUND Allergens from cat are among the most potent elicitors of allergic disease. Four cat allergens have been identified; however, evidence indicates the existence of additional allergens. OBJECTIVE In this study, we evaluated IgE sensitization to IgA from cat. METHODS Sera from cat-sensitized patients (n = 81) were analyzed for IgE antibodies to purified cat IgA in the Pharmacia CAP System. Indirect ELISA was performed with cat IgA, cat IgM, and deglycosylated cat IgA. Competitive inhibition ELISA was performed with cat IgA, cat IgM, calf intestine alkaline phosphatase (CIP), and cat serum albumin on solid phase bound cat IgA. IgE reactivity was also evaluated on membrane blotted cat IgA. RESULTS Thirty-eight percent (31/81) of the cat-sensitized sera were ImmunoCAP-positive to cat IgA. Indirect ELISA demonstrated a high correlation between IgE reactivity to cat IgA and cat IgM (r = 0.94; P < .001). Very low responses were observed to deglycosylated IgA. Strong inhibition of cat IgA was observed in all sera after preincubation with cat IgA and cat IgM. Inhibition was also observed in most sera after preincubation with CIP. Immunoblotting demonstrated that the IgE reactivity was mainly directed to the heavy chain of IgA. CONCLUSION This study has revealed a new allergen, cat IgA, containing a novel group of cross-reactive epitopes depending on carbohydrates also present on IgM and partially on CIP. CLINICAL IMPLICATIONS This new group of cross-reactive carbohydrate IgE epitopes should be taken into consideration when diagnosing patients with suspected animal allergy.
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Affiliation(s)
- Justus Adédoyin
- Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet, University Hospital, Stockholm, Sweden.
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Gafvelin G, Parmley S, Neimert-Andersson T, Blank U, Eriksson TLJ, van Hage M, Punnonen J. Hypoallergens for allergen-specific immunotherapy by directed molecular evolution of mite group 2 allergens. J Biol Chem 2006; 282:3778-87. [PMID: 17170112 DOI: 10.1074/jbc.m607938200] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Allergen-specific immunotherapy is the only treatment that provides long lasting relief of allergic symptoms. Currently, it is based on repeated administration of allergen extracts. To improve the safety and efficacy of allergen extract-based immunotherapy, application of hypoallergens, i.e. modified allergens with reduced IgE binding capacity but retained T-cell reactivity, has been proposed. It may, however, be difficult to predict how to modify an allergen to create a hypoallergen. Directed molecular evolution by DNA shuffling and screening provides a means by which to evolve proteins having novel or improved functional properties without knowledge of structure-function relationships of the target molecules. With the aim to generate hypoallergens we applied multigene DNA shuffling on three group 2 dust mite allergen genes, two isoforms of Lep d 2 and Gly d 2. DNA shuffling yielded a library of genes from which encoded shuffled allergens were expressed and screened. A positive selection was made for full-length, high-expressing clones, and screening for low binding to IgE from mite allergic patients was performed using an IgE bead-based binding assay. Nine selected shuffled allergens revealed 80-fold reduced to completely abolished IgE binding compared with the parental allergens in IgE binding competition experiments. Two hypoallergen candidates stimulated allergen-specific T-cell proliferation and cytokine production at comparable levels as the wild-type allergens in patient peripheral blood mononuclear cell cultures. The two candidates also induced blocking Lep d 2-specific IgG antibodies in immunized mice. We conclude that directed molecular evolution is a powerful approach to generate hypoallergens for potential use in allergen-specific immunotherapy.
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Affiliation(s)
- Guro Gafvelin
- Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet, 17176 Stockholm, Sweden.
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Abstract
The asparagine-linked carbohydrate moieties of plant and insect glycoproteins are the most abundant environmental immune determinants. They are the structural basis of what is known as cross-reactive carbohydrate determinants (CCDs). Despite some structural variation, the two main motifs are the xylose and the core-3-linked fucose, which form the essential part of two independent epitopes. Plants contain both epitopes, insect glycoproteins only fucose. These epitopes and other fucosylated determinants are also found in helminth parasites where they exert remarkable immunomodulatory effects. About 20% or more of allergic patients generate specific anti-glycan IgE, which is often accompanied by IgG. Even though antibody-binding glycoproteins are widespread in pollens, foods and insect venoms, CCDs do not appear to cause clinical symptoms in most, if not all patients. When IgE binding is solely due to CCDs, a glycoprotein allergen thus can be rated as clinical irrelevant allergen. Low binding affinity between IgE and plant N-glycans now drops out as a plausible explanation for the benign nature of CCDs. This rather may result from blocking antibodies induced by an incidental 'immune therapy' ('glyco-specific immune therapy') exerted by everyday contact with plant materials, e.g. fruits or vegetables. The need to detect and suppress anti-CCD IgE without interference from peptide epitopes can be best met by artificial glycoprotein allergens. Hydroxyproline-linked arabinose (single beta-arabinofuranosyl residues) has been identified as a new IgE-binding carbohydrate epitope in the major mugwort allergen. However, currently the occurrence of this O-glycan determinant appears to be rather restricted.
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Affiliation(s)
- Friedrich Altmann
- Divison of Biochemistry, Department of Chemistry, University of Natural Resources and Applied Life Sciences, Vienna, Austria.
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