Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling? The MeDALL hypothesis.
Allergic diseases [asthma, rhinitis and atopic dermatitis (AD)] are complex. They are associated with allergen-specific IgE and nonallergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono- and polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE-mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re-occurrence of foetal type 2 signalling. Asthma, rhinitis and AD are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This study proposes a new classification of IgE-mediated allergic diseases that allows the definition of novel phenotypes to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis and (iii) propose novel strategies of treatment and prevention.
University Hospital, Montpellier, France.|MACVIA-LR, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon, European Innovation Partnership on Active and Healthy Ageing Reference Site, Paris, France.|INSERM, VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches, U1168, Paris, France.|UVSQ, UMR-S 1168, Université Versailles St-Quentin-en-Yvelines, Versailles, France.
J
J
Bousquet
Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Hospital del Mar Research Institute (IMIM), Barcelona, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.|Department of Experimental and Health Sciences, University of Pompeu Fabra (UPF), Barcelona, Spain.
J M
JM
Anto
Sachs' Children's Hospital, Stockholm, Sweden.|Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
M
M
Wickman
Institute of Social Medicine, Epidemiology and Health Economics, Charité - Universitätsmedizin Berlin, Berlin, Germany.|Institute for Clinical Epidemiology and Biometry, University of Wuerzburg, Wuerzburg, Germany.
T
T
Keil
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
R
R
Valenta
Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland.
T
T
Haahtela
Department of Paediatrics, Oslo University Hospital, Oslo, Norway.|Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
K
K
Lodrup Carlsen
Clinical Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet and University Hospital, Stockholm, Sweden.
M
M
van Hage
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
C
C
Akdis
ENT Department, Ghent University Hospital, Gent, Belgium.
C
C
Bachert
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
M
M
Akdis
European Institute for Systems Biology and Medicine, Lyon, France.
C
C
Auffray
EPAR U707 INSERM, Paris, France.|EPAR UMR-S UPMC, Paris VI, Paris, France.
I
I
Annesi-Maesano
Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark.
C
C
Bindslev-Jensen
UMR Inserm U1027, Université de Toulouse III Paul Sabatier, Toulouse, France.
A
A
Cambon-Thomsen
Department of Paediatrics, Oslo University Hospital, Oslo, Norway.|University of Oslo, Oslo, Norway.
K H
KH
Carlsen
Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
L
L
Chatzi
Department of Epidemiology, Regional Health Service Lazio Region, Rome, Italy.
F
F
Forastiere
Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Hospital del Mar Research Institute (IMIM), Barcelona, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.|Department of Experimental and Health Sciences, University of Pompeu Fabra (UPF), Barcelona, Spain.
J
J
Garcia-Aymerich
Julius Center of Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands.
U
U
Gehrig
Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
S
S
Guerra
Institute of Epidemiology, German Research Centre for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany.
J
J
Heinrich
Department of Pediatric Pulmonology and Pediatric Allergology, GRIAC Research Institute, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, the Netherlands.
G H
GH
Koppelman
Department of Immunology, Rheumatology and Allergy, Medical University of Lodz, Lodz, Poland.
M L
ML
Kowalski
VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
B
B
Lambrecht
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
C
C
Lupinek
Biomay AG, Wien, Austria.
D
D
Maier
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
E
E
Melén
Department of Public Health and Biostatistics, EA 4064, Paris Descartes University, Paris, France.|Paris Municipal Department of Social Action, Childhood, and Health, Paris, France.
I
I
Momas
EFA European Federation of Allergy and Airways Diseases Patients' Associations, Brussels, Belgium.
S
S
Palkonen
Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
M
M
Pinart
Department of Respiratory Medicine, GRIAC Research Institute, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, the Netherlands.
D
D
Postma
Inserm, U823, Grenoble, France.
V
V
Siroux
Julius Center of Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands.
H A
HA
Smit
Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Hospital del Mar Research Institute (IMIM), Barcelona, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.|Department of Experimental and Health Sciences, University of Pompeu Fabra (UPF), Barcelona, Spain.
J
J
Sunyer
Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, UK.
J
J
Wright
Allergy-Centre-Charité at the Department of Dermatology, Charité - Universitätsmedizin Berlin, Berlin, Germany.|Secretary General of the Global Allergy and Asthma European Network (GA2LEN), Berlin, Germany.
T
T
Zuberbier
David Hide Asthma and Allergy Research Centre, Isle of Wight, UK.
S H
SH
Arshad
INSERM, VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches, U1168, Paris, France.|UVSQ, UMR-S 1168, Université Versailles St-Quentin-en-Yvelines, Versailles, France.
R
R
Nadif
Department of Epidemiology, CAPHRI School of Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands.
C
C
Thijs
Sachs' Children's Hospital, Stockholm, Sweden.|Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
N
N
Andersson
Sachs' Children's Hospital, Stockholm, Sweden.|Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
A
A
Asarnoj
Sachs' Children's Hospital, Stockholm, Sweden.|Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
N
N
Ballardini
European Institute for Systems Biology and Medicine, Lyon, France.
S
S
Ballereau
MACVIA-LR, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon, European Innovation Partnership on Active and Healthy Ageing Reference Site, Paris, France.
A
A
Bedbrook
Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
M
M
Benet
Sachs' Children's Hospital, Stockholm, Sweden.|Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
A
A
Bergstrom
Julius Center of Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands.
B
B
Brunekreef
INSERM, VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches, U1168, Paris, France.|UVSQ, UMR-S 1168, Université Versailles St-Quentin-en-Yvelines, Versailles, France.
E
E
Burte
National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital NHS, London, UK.
M
M
Calderon
EFA European Federation of Allergy and Airways Diseases Patients' Associations, Brussels, Belgium.
G
G
De Carlo
Department of Respiratory Diseases, Montpellier University Hospital, Montpellier, France.
P
P
Demoly
Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark.
E
E
Eller
Department of Medicine and Public Health, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
M P
MP
Fantini
VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
H
H
Hammad
Institute of Social Medicine, Epidemiology and Health Economics, Charité - Universitätsmedizin Berlin, Berlin, Germany.
C
C
Hohman
Allergology Department, Centre de l'Asthme et des Allergies, Hôpital d'Enfants Armand-Trousseau (APHP), Paris, France.|Institut Pierre Louis d'Epidémiologie et de Santé Publique, Equipe EPAR, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Paris, France.
J
J
Just
Department of Respiratory Medicine, GRIAC Research Institute, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, the Netherlands.
M
M
Kerkhof
Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Hospital del Mar Research Institute (IMIM), Barcelona, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.|Department of Experimental and Health Sciences, University of Pompeu Fabra (UPF), Barcelona, Spain.
M
M
Kogevinas
Sachs' Children's Hospital, Stockholm, Sweden.|Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
I
I
Kull
Department for Pediatric Pneumology and Immunology, Charité Medical University, Berlin, Germany.
S
S
Lau
European Institute for Systems Biology and Medicine, Lyon, France.
N
N
Lemonnier
Department of Epidemiology, CAPHRI School of Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands.
M
M
Mommers
Department of Pediatric Pulmonology and Pediatric Allergology, GRIAC Research Institute, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, the Netherlands.
M
M
Nawijn
Biomay AG, Wien, Austria.
A
A
Neubauer
Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, UK.
S
S
Oddie
European Institute for Systems Biology and Medicine, Lyon, France.
J
J
Pellet
Département de pédiatrie, CHU de Grenoble, Grenoble Cedex 9, France.
I
I
Pin
Department of Epidemiology, Regional Health Service Lazio Region, Rome, Italy.
D
D
Porta
VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
Y
Y
Saes
Department of Paediatrics, Oslo University Hospital, Oslo, Norway.|Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
I
I
Skrindo
Institute of Epidemiology, German Research Centre for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany.
C G
CG
Tischer
Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Area de Salut de Menorca, ib-salut, Illes Balears, Spain.
M
M
Torrent
Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland.
L
L
von Hertzen
D000485:Allergens / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism*; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology*; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D015398:Signal Transduction
D000485:Allergens; D007073:Immunoglobulin E
IgE; asthma; atopic dermatitis; polysensitization; rhinitis