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Resume Les examens biologiques d’allergie contribuent de facon significative au diagnostic et au suivi des allergies aux piqures et morsures d’arthropodes. Les dosages d’IgE specifiques apportent la preuve d’un mecanisme allergique IgE-dependant. L’utilisation rationnelle des outils biologiques disponibles selon les donnees actualisees de la science est a meme de garantir l’efficience diagnostique. Le mesusage de la biologie de l’allergie et/ou leur interpretation erronee risque d’aboutir a des attitudes therapeutiques inadaptees. Consciente de cet enjeu, la Societe francaise d’allergologie (SFA) a mis en place un groupe de travail multidisciplinaire pour l’actualisation des recommandations de biologie de l’allergie, les precedentes recommandations elaborees en 2005 par la Haute autorite de sante (HAS) etant devenues en partie obsoletes en raison de l’evolution des techniques et concepts. La methodologie utilisee est celle des recommandations pour la pratique clinique (RPC) elaboree par la HAS, meme si le texte n’a pas ete labellise par celle institution. Le groupe de travail a redige 8 recommandations gradees sur l’allergie aux piqures et morsures d’arthropodes et 5 recommandations gradees sur d’autres pathologies immuno-allergiques ou frontiere. Bien que non exhaustives, ces 13 questions repondent aux preoccupations les plus courantes des prescripteurs qu’ils soient allergologues ou non, tout en tenant compte du contexte reglementaire francais.

Resume Contrairement aux allergies respiratoires, alimentaires et aux venins d’hymenopteres qui concernent des allergenes proteiques, la prise en charge des allergies aux medicaments necessite rarement le recours aux examens biologiques pour obtenir la preuve d’un mecanisme allergique IgE-dependant. Un nombre tres restreint de dosages d’IgE specifiques de medicaments est disponible car la grande majorite des medicaments sont des haptenes. L’utilisation rationnelle des outils biologiques disponibles selon les donnees actualisees de la science est a meme de garantir l’efficience diagnostique. Le mesusage de la biologie de l’allergie et/ou leur interpretation erronee risque d’aboutir a des attitudes therapeutiques inadaptees voire dangereuses. Consciente de cet enjeu, la Societe francaise d’allergologie (SFA) a mis en place un groupe de travail multidisciplinaire pour l’actualisation des recommandations de biologie de l’allergie, les precedentes recommandations elaborees en 2005 par la Haute autorite de sante (HAS) etant devenues en partie obsoletes en raison de l’evolution des techniques et concepts. La methodologie utilisee est celle des recommandations pour la pratique clinique (RPC) elaboree par la HAS, meme si le texte n’a pas ete labellise par celle institution. Le groupe de travail a redige 11 recommandations gradees sur l’allergie aux medicaments. Bien que non exhaustives, ces 11 questions repondent aux preoccupations les plus courantes des prescripteurs qu’ils soient allergologues ou non pour la prise en charge des patients ayant une suspicion d’allergie aux medicaments, tout en tenant compte du contexte reglementaire francais.

Resume En France, 20 a 25 % de la population generale souffrent d’une maladie allergique. Les allergies respiratoires, preponderantes et au premier rang des maladies chroniques de l’enfant, sont majoritairement dues aux grains de pollen d’arbres et de plantes anemophiles. Les sensibilisations croisees entre des pollens et certains aliments sont de plus en plus frequentes, etendant ainsi le profil symptomatique du respiratoire au digestif voire a la reaction anaphylactique en presence de cofacteurs. Certaines familles de proteines allergisantes impliquees dans le syndrome pollen-aliment sont bien caracterisees du point de vue moleculaire et clinique : la famille des PR-10 dont le prototype est Bet v 1, allergene majeur du pollen de bouleau, les lipotransferases non specifiques, les profilines et les proteines Thaumatin-like. Le mecanisme du syndrome peche-cypres a ete recemment precise grâce a la mise en evidence dans le pollen de cypres d’un allergene de la famille des proteines regulees par la gibberelline (Gibberellin-regulated proteins : GRP) (Cup s 7) responsable de la primo-sensibilisation chez de nombreux patients allergiques a la peche. Le premier allergene de la famille des snakin/GRP, la peamacleine ou Pru p 7, a ete decrit en 2013 dans la peche, puis dans d’autres fruits comme l’abricot japonais, l’orange, et la grenade. Le rechauffement climatique induit une redistribution des especes allergisantes vers les regions du nord. Il allonge la periode de pollinisation et est un facteur important favorisant les pollutions atmospheriques qui augmentent le pouvoir allergisant des pollens et la sensibilite des personnes atopiques.

Resume L’evolution des connaissances, des techniques et la mise a disposition en routine d’un nombre important d’allergenes moleculaires, ainsi que les evolutions reglementaires qui ont fait disparaitre certains extraits allergeniques pour prick tests, ont eu des repercussions sur le diagnostic biologique de l’allergie. La ociete francaise d’allergologie a constitue un groupe de travail, dont l’objectif etait d’actualiser les recommandations de biologie de l’allergie initialement elaborees par la HAS 2 en 2005. La methodologie utilisee pour la redaction est celle de la « Recommandation de bonne pratique », selon la methode « Recommandation pour la pratique clinique » de la HAS. Elle a permis d’elaborer 73 recommandations gradees selon le niveau de preuves, destinees a tous les prescripteurs, dont les principales sont decrites ici.

Resume La verification d’une methode de dosage selon la norme NF/EN/ISO 15189 requiert l’analyse des performances de la technique (repetabilite, fidelite intermediaire, exactitude et incertitude de mesure) avant toute utilisation en routine. Les coefficients de variation (CV) des resultats de precision intra-essai et inter-essais obtenus doivent etre compares a ceux des pairs et a ceux qui pratiquent ces memes dosages quelle que soit la technique. En l’absence de publications nationales ou internationales pour les IgE specifiques et la tryptase, le reseau des biologistes des centres hospitaliers AllergoBioNet a analyse les resultats fournis par 24 centres pour proposer des limites acceptables des criteres de performance pour le dosage des IgE totales et specifiques et de la tryptase.

Resume Les cypres comprennent 160 especes dont les principaux representants sont Cupressus et Hesperocyparis autour du bassin mediterraneen, Juniperus aux Etats-Unis et Cryptomeria au Japon. Leur pollen, abondant en saison est tres allergenique et responsable de rhinoconjonctivite, asthme et toux chronique. Quatre groupes d’allergenes, agrees WHO/IUIS, sont decrits : le groupe 1, une pectate lyase, allergene majeur, marqueur specifique de l’allergie au cypres, le groupe 2, des polygalacturonases, le groupe 3, des proteines thaumatin-like et le groupe 4 correspondant a des proteines fixant le calcium. En 2010, un allergene cationique de petite taille, BP14, sensibilisant principalement les patients allergiques au pollen de cypres du sud-est de la France a ete decrit. L’allergene, de pertinence clinique, appartient a une famille de proteine non decrite comme allergene dans le pollen, les snakin/gibberellin regulated proteins (GRP), petites proteines cationiques possedant des proprietes antimicrobiennes. La gibberelline est une phytohormone qui controle differentes voies metaboliques, dont la reponse au stress biotique et abiotique. Des allergenes de la famille snakin/GRP ont ete caracterises dans la peche (Pru p 7), les agrumes (Cit s 7), l’abricot du Japon (Pru m 7) et la grenade (Pun g 7). BP14 croise avec Pru p 7 et Cit s 7, ce qui explique les syndromes cliniques associes decrits cypres/peche et cypres/agrumes. Une vingtaine d’autres allergenes est, par ailleurs, repertoriee dans la litterature. Les etudes d’allergologie moleculaire sur ce pollen permettent de comprendre les reactions croisees soutenues par les donnees cliniques et ainsi d’accroitre la precision du diagnostic et du traitement immunotherapeutique.

Immunoglobulin-E mediated-cow's milk allergy (IgE-CMA) is the one of the most frequent IgE mediated-food allergy in children in industrialized countries and may cause life- threatening anaphylaxis. The natural history of CM IgE mediated food allergy is favorable for most children. However, the clinical outcome of CMA seems worse than previously described, with less chance of recovery after the age of 31. This article is protected by copyright. All rights reserved.

Early diagnosis of dopamine and serotonin metabolic defects is of importance notably because of the availability of therapeutic strategies able to prevent the associated progressive brain dysfunction. The diagnosis of these diseases relies on the determination of monoamine metabolites and pterins in cerebrospinal fluid (CSF). Current methods involve at least two high-performance liquid chromatography runs of CSF analysis. The first one is devoted to the quantification of dopamine and serotonin metabolites and the second one to the quantification of pterins. Here, we describe a single-step method to measure monoamine neurotransmitter metabolites and pterins of interest in less than 10 min by ultrahigh-performance liquid chromatography coupled to sequential coulometric oxidation and fluorescence detections. All target compounds were quantified in CSF with a small volume (50 μL) and a single filtration step for sample preparation and analysis. After validation, the proposed method was applied to the determination of age-related reference ranges in the CSF of target compounds from a series of 1372 samples collected in France from 2008 to 2014. In the same period, the results obtained for 19 CSF samples from patients with known neurotransmitter disorders and 115 CSF samples with known immune system activation confirmed the expected pattern of changes in monoamine metabolites and pterins.

Introduction Les proteines regulees par l’hormone de plante Gibberelline (GRP pour Gibberellin-regulated protein) sont des allergenes dans 4 fruits (peche, abricot japonais, agrumes et grenade) et dans le pollen d’au moins trois arbres de la famille des Cupressacees, le cypres de Provence, le cedre du Japon et le genevrier d’Ashe. Elles sont produites en reponse a un stress de la plante et possedent une activite anti-microbienne. Resultats Ce sont des petites proteines cationiques, monomeriques, non glycosylees avec 6 ponts disulfures, aux epitopes IgE conformationnels. Elles sont resistantes a la trypsine et a la chaleur. La sequence complete de Cup s 7 a ete determinee par Next Generation Sequencing. Elle corrobore la sequence d’un peptide interne obtenue par spectrometrie de masse et la sequence N-terminale obtenue par la technique d’Edman. Sa conformation lui donne une masse moleculaire apparente de 14 000 Da en conditions non reduites en SDS-PAGE, 8359 Da en centrifugation analytique et 6821 Da calculee a partir de la sequence. Elle sensibilise 40 % des patients allergiques au pollen de cypres (PAPC) et la proteine purifiee active des basophiles de PAPC. Avec 66 % d’identite de sequences, des reactivites croisees IgE sont observees avec la GRP d’orange Cit s 7, de peche Pru p 7 et de grenade Pun g 7, expliquant les syndromes pollen/aliments cypres/peche et cypres/agrumes. La snakine-1, GRP de pomme de terre, non decrite comme allergene, partage 60 % d’identite de sequence avec Cup s 7, suffisant pour observer une reactivite croisee IgE mais pas suffisant pour activer des basophiles de PAPC Cup s 7+. Cup s 7 et Cry j 7 ont 92 % d’identite de sequence. La modelisation moleculaire 3D de Cup s 7 ou de Pru p 7 montre une crevasse dans la molecule, probable site d’interaction avec un ligand potentiel. Quatre epitopes peuvent etre predits. Conclusion La sensibilisation aux GRP pourrait etre un marqueur des syndromes pollen/aliments dont la prevalence augmente. L’hormone gibberelline est utilisee comme traitement dans l’industrie agro-alimentaire. Ce traitement ou autre stress telle que la pollution pourraient entrainer la surproduction de GRP favorisant ainsi la sensibilisation d’individus predisposes.

International audience; A pollen/food-associated syndrome (PFAS) has been described between peach and cypress pollen. Cross-reactive allergens were characterized which belong to the Gibberellinregulated protein (GRP) family, BP14 in cypress pollen and Pru p 7 in peach. GRP are small cationic protein with anti-microbial properties. A patient suffering from a peach/cypress syndrome was explored clinically and biologically using 2 types of immunoglobulin E (IgE) multiarray microchip, immunoblots and a basophil activation test to assess the clinical relevance of various extracts and purified allergens from fruits or cypress pollen. In addition to PR10 sensitization, the patient showed specific IgE to Pru p 7, BP14 and allergen from pomegranate. These last 3 allergens and allergenic sources are able to induce ex vivo basophil activation characterized by the monitoring of the expression of CD63 and CD203c, both cell surface markers correlated with a basophil mediator release. Up to 100% of cells expressed CD203c at 50 ng/mL of BP14 protein. In contrast, snakin-1, a GRP from potato sharing 82% sequence identity with Pru p 7 did not activate patient's basophils. These results strongly suggest that, like Pru p 7, BP14 is a clinically relevant allergenic GRP from pollen. Allergen members of this newly described protein family are good candidates for PFAS where no cross-reactive allergens have been characterized.

Introduction L’etiquetage des allergenes alimentaires est soumis a une reglementation europeenne avec une liste de 14 allergenes a declaration obligatoire (DO), dont le lait de vache (LDV). Methodes Nous decrivons le cas d’un enfant de 18 mois suivi depuis l’âge de 6 mois pour une allergie IgE-mediee aux proteines de LDV a seuil bas. Apres ingestion d’un biscuit au chocolat noir, fabrique par une biscuiterie familiale dite « bio et artisanale », il a presente une anaphylaxie de grade 2. Il consommait regulierement ces memes biscuits sans manifestation allergique jusqu’alors. Resultats L’etiquette du produit, inchangee, mentionne un simple etiquetage de precaution : « peut contenir du lait ». Le reste des ingredients est consomme par l’enfant sans reaction clinique. Les Prick-tests realises avec le lot du gâteau sont positifs pour la partie chocolatee du biscuit et negatifs pour le reste du biscuit. L’IgE caseine est a 25 KU/L. Le service consommateur nous a informe que ce gâteau provenait d’un lot fabrique immediatement apres la fabrication d’un lot de gâteaux au chocolat au lait, expliquant la contamination du chocolat noir par le lait. Un Western Blot a ete realise a partir des differentes parties du gâteau confirmant la presence de lait dans la partie chocolatee. Discussion Les produits artisanaux sont souvent issus d’entreprises familiales qui ont plus de difficultes qu’une grande entreprise, a assurer l’absence de contamination des produits dans la chaine de production. Conclusion L’education therapeutique des patients allergiques et la vigilance vis a vis de l’etiquetage de precaution sont fondamentales pour diminuer le risque d’accidents allergiques.

International audience; What is already known about this topic? Peanut allergy is one of the most frequent causes of anaphylaxis in children with food allergies. Oral food challenge remains the gold standard to evaluate the threshold dose and severity of peanut allergy. What does this article add to our knowledge? This study reports the relevance of allergen-specific and noneallergen-specific basophil activation test parameters to determine the severity and threshold dose of a peanut-allergic reaction in children. How does this study impact current management guidelines? Introduction of these multivariable models in routine practice could avoid an oral food challenge in some children with peanut allergy. BACKGROUND: Safe and cost-effective biological surrogate markers to evaluate the severity and threshold dose of peanut allergy (PA) reactions during an oral food challenge (OFC) are lacking. OBJECTIVE: To evaluate biological markers associated with the severity and threshold dose of an allergic reaction during an OFC in a population of children with PA. METHODS: Demographic and biological parameters of children with peanut OFC and basophil activation test (BAT) results were collected. Patients were stratified into 2 severity groups (mild-to-moderate and severe) and 2 cumulative threshold dose groups: low (LCTG) £100 mg crushed peanut and high >100 mg. RESULTS: Among the 68 children included, there was a 96% concordance between the OFC and BAT result for the diagnosis of PA. Of the 56 children with a positive OFC and BAT to peanut (median age: 8.8 years), the severity of an allergic reaction and the cumulative threshold dose were not correlated (P [ .24). Higher Ara h 2especific IgE and FcεRI-positive control values were both associated with severe reactions to peanut. Combining these 2 markers led to a 92% sensitivity (84%-97%) and an 82% specificity (71%-89%) for severe

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.

Background Allergic sensitisation is poorly documented in infants. This study aims to provide new insights into allergic sensitisation patterns and related factors in infancy. Methods This study concerns 1860 infants involved in the Pollution and Asthma Risk: an Infant Study (PARIS) population-based birth cohort who had a standardised health examination when 18 months old, from 2004 to 2008. Sensitisation was assessed by measurements of serum specific IgE to 12 food and 4 inhalant allergens and defined by IgE ≥ 0.35 kUA/L. Information regarding lifestyle and environment were obtained from questionnaires prospectively administered. Results Prevalence of allergic sensitisation to any allergen, to food allergens, and to aeroallergens was 13.8%, 12.3%, and 2.3%, respectively. Multiple sensitisation (to at least two allergens) concerned 6.2% of toddlers. Intrinsic factors such as male gender, family history of allergy, and high birth weight increased the risk of food allergen sensitisation and multiple sensitisation. Caesarean section was also positively associated with multiple sensitisation. Day-care attendance was negatively related to food allergen, aeroallergen, and multiple sensitisation. A cat entering the baby’s room in early life was strongly associated with aeroallergen sensitisation (ORa 3.21, 95%CI: 1.29–8.01). An introduction of meat in infant’s diet after 6 months of age was negatively related to food allergen sensitisation (ORa 0.46, 95%CI: 0.24–0.91). Conclusion Our results suggest that intrinsic factors and indicators of exposure to microorganisms such as caesarean section and day-care attendance may be associated with inhalant as well as food allergen sensitisation in infancy. For example, male gender, family history of allergy, high birth weight, and caesarean section could be positively related whereas day-care attendance could be negatively related to both aeroallergen and food allergen sensitisation. Conversely, early life exposure to inhalant allergens or food allergens may be specifically linked to either aeroallergen sensitisation or food allergen sensitisation, respectively.

Introduction L’omalizumab est une biotherapie indiquee chez l’enfant presentant un asthme allergique severe. Il est donc important de definir plus clairement la population cible qui peut beneficier au mieux de cette biotherapie. Objectifs Le but de cette etude est de definir les facteurs predictifs de reponse complete a l’omalizumab a 4 mois de traitement. Methodes Nous avons inclus retrospectivement des enfants presentant un asthme severe ou refractaire traite par omalizumab. La reponse complete a l’omalizumab etait evaluee a 4 mois lors d’une reunion multidisciplinaire (en tenant compte de l’ACT, des exacerbations severes, des EFR) et classee en reponse partielle, complete ou non reponse. Resultats Pour les 45 inclus dans l’etude, 22 patients (49 %) avaient une reponse complete, 20 (44 %) une reponse partielle, et 3 (7 %) etaient non repondeurs. Dans l’analyse par regression logistique la presence d’un eczema et un VEMS eleve etaient des facteurs predictifs de reponse complete a l’omalizumab a 4 mois (en comparaison aux non-repondeurs ou aux repondeurs partiels) avec un OR de 1,50 (IC 95 % [1,09 ; 1,9], p = 0,005), et 1,02 (IC 95 % [1,01 ; 1,20], p = 0,001), respectivement. Nous avons identifie 3 clusters independants de reponse a l’omalizumab. Cluster 1, 16 patients avec un asthme eosinophilique (eosinophilie > 300/mm3, n = 15 (94 %), p = 0,001), VEMS moyen 65,4 ± 10,2, (p = 0,006) avec une faible reponse a l’omalizumab (n = 1 (6 %), p Conclusion De multiples morbidites allergiques (dont l’eczema) avec des sensibilisations allergiques multiples et une fonction pulmonaire normale s’associent a une reponse precoce a l’omalizumab.

Introduction Le fullerene est une sphere de 1 nm de diametre composee de 60 atomes de carbones en forme de ballon de football. Ses 30 double-liaisons lui conferent une grande affinite pour les radicaux libres et cette propriete a ete exploree dans le stress oxydant ou l’equilibre redox est implique, dans des situations pathophysiologiques inflammatoires telle que l’allergie. Methodes Le compartiment cellulaire cible par les fullerenes a ete etudie apres injection in vivo chez la souris, et recherche dans le foie par microscopie electronique et mesure de l’activite d’enzymes de la chaine respiratoire. L’effet des fullerenes sur l’activation des cellules impliquees dans l’allergie a ete etudie, in vitro sur la lignee cellulaire mastocytaire RBL-2H3 et ex vivo sur le sang de patients allergiques dans un test d’activation des basophiles. Pour rendre les fullerenes solubles dans les milieux aqueux ils ont ete greffes avec : des radicaux OH (fullerol), du serinol-malonate, de la β-cyclodextrine ou des dendromeres. Resultats Apres injection chez la souris, les fullerenes sont retrouves dans le foie, dans les mitochondries avec des modifications limitees mais specifiques de l’activite des enzymes de la chaine respiratoire. In vitro les derives de fullerenes ne sont pas toxiques sauf la cyclodextrine fullerene. La degranulation IgE-dependante et -independante des cellules RBL-2H3 a ete significativement inhibee a des concentrations nanomolaires par le dendro-fullerene. Les differents derives sont capables d’interferer ex vivo avec l’activation de basophiles de patients allergiques en sang total et le taux d’inhibition de l’expression de CD63 et CD203c depend des derives et des patients (maximum : 35 % avec le serinol-malonate fullerene). Discussion Le serinol-malonate et le dendro fullerene ont des index d’inhibition les plus reproductibles. Les mecanismes d’action au niveau cellulaire restent a definir. Ces inhibitions ont ete reproduites sur des basophiles humains purifies en etudiant les marqueurs CD107a et CD69. Conclusion En accord avec leur capacite anti-oxydante les fullerenes in vivo ciblent preferentiellement les mitochondries. Ils sont capables d’interferer avec les mecanismes de degranulation des basophiles.

Supplementation with arginine in combination with atorvastatin is more efficient in reducing the size of an atherosclerotic plaque than treatment with a statin or arginine alone in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits. We evaluated the mechanism behind this feature by exploring the role of the arginine/asymmetric dimethylarginine (ADMA) ratio, which is the substrate and inhibitor of nitric oxide synthase (NOS) and thereby nitric oxide (NO), respectively. Methods: Rabbits were fed either an arginine diet (group A, n = 9), standard rabbit chow plus atorvastatin (group S, n = 8), standard rabbit chow plus an arginine diet with atorvastatin (group SA, n = 8) or standard rabbit chow (group C, n = 9) as control. Blood was sampled and the aorta was harvested for topographic and histological analysis. Plasma levels of arginine, ADMA, cholesterol and nitric oxide were determined and the arginine/ADMA ratio was calculated. Results: The decrease in ADMA levels over time was significantly correlated to fewer aortic lesions in the distal aorta and total aorta. The arginine/ADMA ratio was correlated to cholesterol levels and decrease in cholesterol levels over time in the SA group. A lower arginine/ADMA ratio was significantly correlated to lower NO levels in the S and C group. Discussion: A balance between arginine and ADMA is an important indicator in the prevention of the development of atherosclerotic plaques.

International audience; At least two pollen food associated syndromes were described with cypress pollen allergy involving peach and citrus. Snakin/gibberellin regulated proteins are described herein to be the cross-reactive allergens between Cupressus sempervirens pollen and fruit/vegetables.

Background Childhood recurrent wheezing and consequently asthma corresponds to various phenotypes. Our aim was to link genetic variants of asthma candidate genes to the phenotypes of early onset wheezing. Study design We included very young consecutive children presenting with recurrent wheezing who had been evaluated for the severity of wheezing, associated atopic comorbidities, and tested for biomarkers of atopy and inflammation. All were genotyped for 16 single nucleotide polymorphisms (SNPs) linked with asthma or atopy. An unsupervised hierarchical bottom-up method was used for clustering the phenotypes and a multinomial logistic regression was performed for each individual SNP. Results We replicated the three phenotypes previously described Trousseau Asthma Program in 317 children aged 21.5 ± 7.9 months: cluster 1 (nonatopic uncontrolled severe wheeze), n = 207, a severe viral-induced wheeze, cluster 2 (atopic multiple trigger wheeze), n = 61, with multiple allergic comorbidities, and cluster 3 (episodic viral wheeze), n = 49, a mild viral-induced wheeze. The TT-genotype of the IL-4 rs2070874 polymorphism was significantly associated with the nonatopic uncontrolled severe wheeze compared to the episodic viral wheeze (OR 7.9; CI95% [2.5-25.3]; P = 0.001). Conclusion Association between the TT-genotype of IL-4 rs2070874 polymorphism and a severe phenotype of viral-induced wheeze further underlines the role IL-4 plays in the inflammation pathway leading to viral respiratory infections.

Background Angiogenesis is essential for the progression and metastatic spread of solid tumours. Expression of vascular endothelial growth factor (VEGF) has been linked to poor survival among osteosarcoma patients but the clinical relevance of monitoring blood and urine angiogenic factors is uncertain. The aim of this study was to determine the prognostic significance of blood VEGF and blood and urinary basic fibroblast growth factor (bFGF) levels in osteosarcoma patients, both at diagnosis and during treatment. Methods Patients with localised or metastatic osteosarcoma enrolled in OS2005 and OS2006 studies between 2005 and 2011 were prospectively included in this study. VEGF and bFGF levels in serum and plasma and bFGF levels in urine were measured by ELISA at diagnosis, before surgery, and at the end of treatment. Endpoints considered for the prognostic analysis were histological response, progression-free and overall survival. Kruskal-Wallis tests were used to compare the distribution of baseline biomarker values across the different subgroups, and paired sample Wilcoxon rank tests were used to analyze changes over time. Association between biomarker levels and outcomes were assessed in multivariable models (logistic regression for histologic response, and Cox models for survival). Results Samples were available at diagnosis for 269 patients (54% males; age ≤ 18 years: 73%; localised disease in 68%, doubtful lung lesions in 17%, and metastases in 15%). High serum VEGF and bFGF levels were observed in respectively 61% and 51% of patients. Serum and plasma VEGF values were not strongly correlated with one another (r = 0.53). High serum and plasma VEGF levels were significantly more frequent in patients with large tumours (≥10 cm; p = 0.003 and p = 0.02, respectively). VEGF levels fell significantly during pre-operative chemotherapy (p

Takcı Ş, Anuk-İnce D, Louha M, Couderc R, Çakar N, Köseoğlu RD, Ateş Ö. A rare large mutation involving two exons of the SP-B gene in an infant with severe respiratory distress. Turk J Pediatr 2017; 59: 483-486. Hereditary surfactant protein-B (SP-B) deficiency is a rare autosomal recessive disease of newborn infants causing severe respiratory failure and death within the first year of life. The most common cause of SP-B deficiency is a frameshift mutation in exon 4 (121ins2) in the gene encoding SP-B. We report a term infant with unremitting respiratory distress who was unresponsive to all treatment modalities. The parents were consanguineous and a term sibling of the infant had died due to respiratory failure without a certain diagnosis. In the first step of the diagnostic work-up, common genetic mutations for SP-B, surfactant protein C and ATP-binding cassette s3 were absent, however sequencing of SP-B gene revealed a large homozygous genomic deletion covering exon 8 and 9. In this case report, we aimed to emphasize further genetic evaluation in all cases suggestive of surfactant dysfunction, even if common mutations are absent.

International audience; BackgroundLittle is known about inflammatory pathways of severe recurrent wheeze in preschool children and severe asthma in children.ObjectivesThe aim of the Severe Asthma Molecular Phenotype cohort was to characterize phenotypes of severe recurrent wheeze and severe asthma during childhood in terms of triggers (allergic or not), involved cells (eosinophil or neutrophil), and corticoid responsiveness.MethodsChildren with moderate-to-severe asthma and preschool children with moderate-to-severe recurrent wheeze were enrolled prospectively. They underwent standardized clinical and blood workup, and bronchoalveolar lavage (BAL) evaluation. Cluster analysis was applied to 350 children with 34 variables.ResultsThree clusters were identified: cluster 1, Neutrophilic steroid-refractory recurrent wheeze phenotype, with 138 children uncontrolled despite high-dose inhaled corticosteroids (ICS) (92%, P < .001), with more history of pneumonia (31%, P < .001), more gastroesophageal reflux disease (37%, P < .001), and the highest blood neutrophil count (mean 4.524 cells/mm3, P = .05); cluster 2, Severe recurrent wheeze with sensitization to a single aeroallergen (12%, P = .002), with 104 children controlled with high-dose ICS (63%, P < .001); cluster 3, Eosinophilic steroid-refractory asthma phenotype, with 108 children uncontrolled despite high-dose ICS (76%, P < .001) with more allergic rhinitis, atopic dermatitis, and food allergies (82%, 40%, 31%, P < .001, respectively). They also had a higher blood eosinophil count and a higher percentage of BAL eosinophil (506/mm3, 2.6%, P < .001 respectively).ConclusionsInflammation pathway of asthma and recurrent wheeze are related to eosinophil cells in older children and neutrophil cells in younger children. These results could improve personalized treatments.

Background Profiles of allergic sensitisation are poorly documented in infancy. Relations between early sensitisation and allergic morbidity need to be clarified. Methods This study dealt with children involved in the Pollution and Asthma Risk: an Infant Study (PARIS), a population-based prospective birth cohort. Allergic sensitisation to 12 food and 4 inhalant allergens was assessed at 18 months and defined by a specific IgE level ≥ 0.35 kUA/L. Health data were collected by standardised questionnaires at 2 and 6 years. Early allergic profiles were identified by an unsupervised cluster analysis based on health data at 2 years and IgE measurements. Profiles were compared with regard to allergic morbidity and multimorbidity at 6 years. Results Sensitisation to any allergen concerned 13.6% of infants. By cluster analysis, 1525 infants were grouped in 3 profiles: 89.2% not or rarely sensitised (only 3.7% of sensitised), 9.2% mainly sensitised to one or few allergens (45.2% of monosensitised and 45.9% of paucisensitised), and 1.6% all polysensitised. The prevalence of doctor-diagnosed asthma, rhinitis, eczema, food allergy, and multimorbidity at 2 years increased from profile 1 to profile 3 (p-trend < 0.001). At 6 years, symptoms of current asthma, rhinitis, eczema, and multimorbidity were significantly more frequent in the last two profiles. Conclusions This study highlights, as early as 18 months of age, 3 profiles of increasing severity with regard to allergic sensitisation and diseases. These profiles also differ in terms of allergic morbidity at 6 years. Early sensitisation can predict allergic multimorbidity in childhood, and in the case of early polysensitisation, multimorbidity is more frequent as soon as infancy. This article is protected by copyright. All rights reserved.

Introduction La prevalence des syndromes associes pollen/aliment est en augmentation que ce soit pour les adultes ou les enfants. Ces syndromes impliquent de nombreux pollen et aliments comme le syndrome pomme/bouleau ou LTP mais d’autres allergenes peuvent etre incrimines. Methodes Apres exploration clinique, les reactivites IgE specifiques des patients selectionnes sont etudiees par test unitaire classique, microarray, immunoempreinte et test d’activation des basophiles. Resultats La decouverte de la peamacleine (allergene Pru p 7 de peche), une proteine regulee par la Gibberelline (GRP), a ete le point de depart de celle d’allergenes de la meme famille dans d’autres fruits et aussi dans le pollen de cypres : BP14. BP14 croise avec Pru p 7, la snakine-1 (GRP de pomme de terre) et une petite proteine cationique des agrumes, probablement Cit s 7 (GRP de l’orange), ce qui a permis de proposer une explication aux syndromes cypres/peche et cypres/agrumes decrits. Ces allergenes sont resistants a la chaleur et a la trypsine et possedent des epitopes IgE conformationnels. La proteine BP14, comme Pru p 7, a une pertinence clinique car elle peut induire ex vivo la degranulation de basophiles d’un patient atteint du syndrome cypres/peche. Ce patient a des IgE specifiques de Pru p 7 et aussi d’une petite proteine cationique de la grenade (probablement Pun g 7), fruit auquel il est allergique. Discussion De nombreuses GRP, petites proteines cationiques, ont ete decrites dans le monde vegetal mais leur allergenicite en tant que pneumallergene ou trophallergene n’a pas fait l’objet de nombreuses publications. Avec des identites de sequences de plus de 80 %, elles seraient candidates aux reactivites croisees IgE. Nos experiences preliminaires d’inhibitions croisees sur Pru p 7, Cit s 7 et BP14 laissent cependant penser qu’il existe une grande diversite de reactivite IgE au sein de cette famille de proteine malgre une faible diversite de structure primaire sur des proteines de faible masse moleculaire. Conclusion Des etudes immunostructurales permettraient de rechercher des differences subtiles de structure tertiaire ou l’existence de cofacteurs/ligands moleculaires impliques dans l’allergenicite de cette famille de proteines.

RESUME L’identification de l’allergene en cause a toujours presente un grand interet pour appliquer des mesures preventives et mettre en œuvre un traitement par l’immunotherapie allergenique (ITA). Depuis la fin des annees 1980, l’application des techniques de clonage moleculaire a la caracterisation des allergenes a permis d’importantes avancees dans la connaissance des epitopes impliques dans l’allergie IgE-mediee et la production in vitro d’allergenes recombinants d’interet pour le diagnostic de sensibilisation allergenique. Cela a aussi facilite la comprehension des reactivites croisees, parfois responsables de manifestations cliniques graves, en particulier chez les enfants qui presentent des allergies alimentaires et un asthme allergique. Enfin la connaissance des mecanismes cellulaires et moleculaires de la sensibilisation allergique grâce aux allergenes recombinants naturels ou modifies a permis d’elaborer des strategies d’ITA efficaces qui permettent d’envisager dans les annees futures des remissions prolongees des patients, permettant d’eviter le recours aux traitements symptomatologiques chroniques, et cela tres precocement dans l’enfance.

International audience; BackgroundThe 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.ObjectiveTo characterize the allergic reaction and identify the potential nettle pollen sensitizing allergens.MethodsIgE-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.ResultsThe 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.ConclusionExposure 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.

Introduction Allergic sensitisation is poorly documented in infants. This study aims to provide new insights into allergic sensitisation patterns and related factors in infancy. Methods This study ...

Introduction La pollinose au cypres touche pres de 40 % de la population allergique mediterraneenne. Plusieurs especes de cypres sont en cause dont le cypres de Provence, Cupressus sempervirens (Cups). Quatre groupes d’allergenes de pollen de cypres sont decrits et references IUIS : groupe 1, allergene majeur, est une pectate lyase, le groupe 2 une polygalacturonase, le groupe 3 une « thaumatin-like protein » et le groupe 4 une proteine liant le calcium. D’autres allergenes ont ete mis en evidence en particulier dans le pollen de Cups ou une proteine basique de 14 kDa, BP14 (non identifiee), est reconnue par les IgE de 25 a 40 % des patients allergiques au pollen de cypres. Methodes La caracterisation de BP14 a ete faite par analyse immunoproteomique, c’est-a-dire immunoempreinte IgE avec des serums de patients allergiques au pollen de cypres associee a la spectrometrie de masse (LC/MS/MS). Resultats L’analyse en MS en utilisant la chymotrypsine a permis d’identifier un peptide present dans la famille de proteine « snakin/gibberellin-regulated protein (GRP) ». La snakine-1 recombinante de pomme de terre, homologue aux 63 acides amines C-terminaux d’une GRP, est reconnue par les IgE de patients allergiques au pollen de cypres BP14+. Cette reactivite est perdue apres reduction des ponts disulfure et est inhibee par un extrait de pollen de Cups. La reactivite IgE vis-a-vis de la BP14 est en revanche tres peu inhibee par la snakin-1 de pomme de terre. Discussion BP14 a une masse moleculaire plus proche de celle des GRP que des snakines et la faible inhibition de la reactivite IgE anti-BP14 par la snakine peut s’expliquer par la presence d’epitopes IgE sur la partie N-terminale de la BP14. La sequence de la snakine-1 de pomme de terre est a 83 % identique a celle de la peamacleine, l’allergene Pru p 7 de la peche. Ce resultat pourrait expliquer le syndrome bien connu peche/cypres pour lequel aucun allergene croisant n’a ete decrit jusqu’a present. Conclusion La famille de proteine snakine/GRP pourrait correspondre a une nouvelle famille de proteine impliquee dans les syndromes pollen/aliment.

Resume Depuis la description de l’ionisation par electro-jet (ESI) en 1968, la spectrometrie de masse est devenue un outil incontournable en biologie medicale. Les recents developpements dans le domaine du couplage de la spectrometrie de masse aux techniques separatives ainsi que les progres dans celui du traitement des donnees en font un outil indispensable pour la recherche et le diagnostic biomedical. La spectrometrie de masse en tandem est couramment utilisee pour le diagnostic et le suivi des maladies hereditaires du metabolisme, notamment pour la realisation du profil des acylcarnitines destine a l’exploration des intermediaires acyl-CoA issus du metabolisme oxydatif des acides gras et de certains acides amines. Elle est egalement utilisee, couplee a la chromatographie liquide, pour le dosage de la creatine et du guanidinoacetate permettant l’analyse du metabolisme de la creatine. Enfin, l’analyse des acides amines peut aussi etre realisee par cette technique. La chromatographie en phase gazeuse couplee a la spectrometrie de masse reste la methode de reference pour l’analyse des acides organiques urinaires. La spectrometrie de masse permet donc, de par sa specificite, l’analyse d’un grand nombre de molecules, et pourrait etre utilisee a l’avenir pour le depistage neonatal de la plupart des maladies metaboliques.

Objective To investigate the implication of SLC26A4, FOXI and KCNJ10 genes in unilateral hearing impairment associated with ipsilateral inner ear malformation (Enlargement of the vestibular aqueduct and/or Mondini dysplasia). Methods We have gathered 25 patients presenting unilateral hearing impairment and ipsilateral enlarged vestibular aqueduct. For each of the patients, we have analyzed SLC26A4, FOXI1 and KCNJ10 genes sequences. Results The analysis of SLC26A4 revealed only eight heterozygous SLC26A4 sequence variants, three of them being novel (p.Met147Ile, p.Asn538Asn and p.Leu627Arg). None of the patients carried a second mutation on the other allele. Moreover, the SLC26A4 locus was excluded by segregation analysis in two families. No mutations were present in FOXI1 and KCNJ10 genes. Conclusions Together, these data suggest that SLC26A4, FOXI1 and KCNJ10 are not major determinants in unilateral deafness and enlarged vestibular aqueduct compared with their implication in Pendred syndrome and non-syndromic bilateral enlarged vestibular aqueduct.

Resume La majorite des desordres affectant le metabolisme des acides amines sont des maladies rares, le plus souvent hereditaires de transmission autosomique recessive et se declarant par des anomalies metaboliques ainsi que des troubles neurologiques ; generalement neonatales, elles peuvent rester longtemps asymptomatiques et etre diagnostiquees seulement a l’âge adulte. Les aminoacidopathies hereditaires (AAH) doivent etre suspectees chez les patients presentant des troubles neurologiques varies accompagnant une symptomatologie aigue a l’origine de l’hospitalisation. Il est particulierement important que les prelevements d’echantillons biologiques soient effectues prealablement a tout traitement ; la majorite des situations d’urgence peut etre elucidee a l’aide de tests simples parmi lesquels la chromatographie des acides amines. Le diagnostic des AAH repose sur un faisceau de presomptions ; certaines aminoacidopathies repondent a un traitement specifique et doivent etre identifiees rapidement surtout en situation d’urgence pour eviter une issue fatale ou une maladie neurologique irreversible. Les traitements necessitent une restriction proteique et la stimulation de voies metaboliques alternatives. Dans cette revue, nous detaillons l’essentiel des aminoacidopathies hereditaires.

Introduction La cohorte Observatoire des Risques Lies a l’Atopie Cutanee (ORLAC) a pour objectif d’identifier les facteurs de risque de developper un asthme chez 250 enfants atteints de dermatite atopique (DA) presentant des allergies alimentaires (arachide entre autres), durant leur premiere annee de vie. Le suivi sur 5–6 annees inclut des questionnaires medicaux, des tests cutanes, la recherche d’eosinophilie sanguine et le dosage d’IgE totales et specifiques. Question : le profil moleculaire de reactivite IgE a Ara chez les enfants a la date d’inclusion est-il predictif de l’evolution vers un asthme rencontree dans 10 a 20 % des cas a l’âge de 5–6 ans ? Methodes Vingt-trois patients ayant evolue vers un asthme (A) et 23 cas controles n’ayant pas evolue vers l’asthme (NA) sont selectionnes. Les proteines d’Ara sont separees par electrophorese en 1 et 2 dimensions (1DE et 2DE) et les reactivites IgE et IgG4 des serums de chaque patient a la date d’inclusion, etudiees par immunoempreinte. Les allergenes reperes sont identifies par spectrometrie de masse. Resultats L’heterogeneite de la reponse IgE anti-proteines d’Ara en immunoempreinte 1DE est semblable dans les 2 groupes. Analyse plus finement en immunoempreinte 2DE, seuls les patients A presentent, vis-a-vis de certaines proteines cationiques, faiblement representees, de faible masse moleculaire (Mr), des reactivites IgE. Aucune difference de reactivite IgE entre les 2 groupes n’est observee pour les allergenes majeurs d’Ara. De facon inattendue, la reponse IgG4 specifique des proteines de l’Ara est qualitativement et quantitativement plus importante chez les patients A que chez les NA. Discussion Les petites proteines cationiques IgE reactives pourraient correspondre aux oleosines allergeniques de l’arachide decrites comme etant associees a des symptomes severes [1] et qui sont presentes dans nos extraits. Conclusion L’etude des reactivites IgE anti-oleosines chez les patients A meriterait d’etre approfondie. Si leur qualite de marqueur de severite est confirmee elle pourrait permettre de proposer une demarche clinique de prevention primaire de l’asthme sur une population a risque atteinte de DA.

Background and purpose: The influence of apolipoprotein E (ApoE) polymorphism on clinical severity of multiple sclerosis (MS) is still controversial. Cigarette smoking has been suggested to influence the progression of disability in these patients. In this study, we aimed to investigate whether an interaction of smoking with the ApoE polymorphism influences the progression of disability in MS patients. Methods: Smoking history from 205 female patients with MS was obtained. Clinical data collected include age at onset, disease duration, annual relapse rate, the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS). ApoE polymorphism was examined in all patients and stratified according to smoking status and associations with the clinical data investigated. Results: There were no significant associations between cigarette smoking and any of the clinical characteristics in the whole group of patients. In women carrying the ApoE E4 isoform, smokers had a lower EDSS (P = 0.033) and MSSS (P = 0.023) in comparison with non-smokers. Conclusion: Our data suggest that in women with MS carrying the ApoE E4 isoform, cigarette smoking may have a protective influence on disease progression and accumulation of disability. These findings need to be confirmed by future large longitudinal studies.

Keratitis-Ichthyosis-Deafness (KID) syndrome (OMIM 148210) is a congenital ectodermal defect. KID consists of an atypical ichthyosiform erythroderma associated with congenital sensorineural deafness. A rare form of the KID syndrome is a fatal course in the first year of life due to severe skin lesion infections and septicaemia. KID appears to be genetically heterogeneous and may be caused by mutations in connexin 26 or connexin 30 genes. GJB2 mutations in the connexin 26 gene are the main cause of the disease. Most of the cases caused by GJB2 mutations are sporadic, but dominant transmission has also been described. To date, the rare lethal form of the disease has been only observed in two Caucasian sporadic patients with the GJB2 mutation, with the p.Gly45Glu (G45E) arising de novo. We have reported an African family with dizygotic twins suffering from a lethal form of KID. The dizygosity of the twins was confirmed by microsatellite markers. The two patients were heterozygous for the G45E mutation of GJB2, whereas the mutation was not detected in the two parents. The unusual transmission of the disease observed in this family could be explained by the occurrence of a somatic or more probably a germinal mosaic in one of the parents.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth condition with tumor proclivity linked to a genetic imbalance of a complex imprinted region in 11p15.5. A female child with features fitting in with the BWS diagnostic framework and an apparent loss of imprinting (LOI) of the IGF2 gene in 11p15.5 was also reported to have a de novo chromosome 18q segmental deletion (Patient 1), thus pointing at the location of a possible trans-activating regulator element for maintenance of IGF2 imprinting and providing one of the few examples of locus heterogeneity of BWS. A second child with de novo 18q23 deletion and features of macroglossia, naevus flammeus, bilateral inguinal hernia and transient neonatal hypoglycemia, thus also fitting in with the BWS diagnostic framework, is here fully reported (Patient 2). In this child, an analysis of the BWS1 locus precluded any paternal isodisomy and showed a normal imprinting pattern (mono-allelic expression of IGF2 and normal H19 and CDKN1OT1/LIT1 methylation index). In Patients 1 and 2, deletions were shown to overlap, defining a minimal region of haplo-insufficiency of 3.8-5.6 Mb in 18q23. We conclude that this region provides a candidate location for an original macroglossia condition with strong overlap with BWS, but without obvious upstream functional relationship with the BWS1 locus in 11p15.5. Because this minimal region of haplo-insufficiency falls into a common region of deletion in 18q- syndrome, we inferred that this macroglossia condition would follow a recessive pattern of inheritance.

Mitochondrial DNA (mtDNA) mutations have been implicated in non-syndromic hearing loss either as primary or as predisposing factors. As only a part of the mitochondrial genome is usually explored in deafness, its prevalence is probably under-estimated. Among 1350 families with non-syndromic sensorineural hearing loss collected through a French collaborative network, we selected 29 large families with a clear maternal lineage and screened them for known mtDNA mutations in 12S rRNA, tRNASer(UCN) and tRNALeu(UUR) genes. When no mutation could be identified, a whole mitochondrial genome screening was performed, using a microarray resequencing chip: the MitoChip version 2.0 developed by Affymetrix Inc. Known mtDNA mutations was found in nine of the 29 families, which are described in the article: five with A1555G, two with the T7511C, one with 7472insC and one with A3243G mutation. In the remaining 20 families, the resequencing Mitochip detected 258 mitochondrial homoplasmic variants and 107 potentially heteroplasmic variants. Controls were made by direct sequencing on selected fragments and showed a high sensibility of the MitoChip but a low specificity, especially for heteroplasmic variations. An original analysis on the basis of species conservation, frequency and phylogenetic investigation was performed to select the more probably pathogenic variants. The entire genome analysis allowed us to identify five additional families with a putatively pathogenic mitochondrial variant: T669C, C1537T, G8078A, G12236A and G15077A. These results indicate that the new MitoChip platform is a rapid and valuable tool for identification of new mtDNA mutations in deafness.

International audience; BackgroundAtopic dermatitis (AD) is known to predate asthma and other atopic disorders described under the term “atopic march”. However, this classic sequence is not always present and only a few studies have addressed children at risk of developing asthma. The objective of this study is to define early-onset AD phenotypes leading to asthma.MethodsWe performed a cluster analysis with 9 variables of 214 infants with early-onset AD prospectively enrolled in the ORCA cohort and followed each year on the occurrence of asthma until the age of 6.ResultsWe identified 3 clusters - cluster 1 (n = 94) with low to no sensitization to food (27.7%) or aeroallergens (10.6%) and moderate AD severity (SCORAD 25.29 +/- 14.6) called “AD with low sensitization”; - cluster 2 (n = 84) characterized by a higher AD severity (SCORAD 32.66+/-16.6) and frequent sensitization to food (98.9%) or aeroallergens (26.2%), most likely multiple (96.4% for food allergens), called “AD with multiple sensitizations” - cluster 3 (n = 36) with parental history, moderate AD severity (SCORAD 24.46+/-15.7), moderate rate of sensitization to food allergens (38.9%) (exclusively single) with no sensitization to aeroallergens, called “AD with familial history of asthma”. Percentages of children suffering from asthma at the age of 6 were higher in clusters 2 and 3 (36.1% and 33.3% respectively versus 14.9% in cluster 1, p

International audience; At present, it is still difficult to distinguish a priori different phenotypes of early-onset asthma in infants, especially to be able to differentiate infants with asthma who are at risk of persistence and severity from those with transient wheezing. It is thus essential to improve the prediction of the prognosis of early-onset asthma because of its high frequency, about 10%, in the pediatric general population. The pulmonary epithelium secretes into the serum a variety of proteins, including some known as pneumoproteins, and these proteins can now be assayed in the serum. Some of them might represent an interesting way in the search of new biomarkers associated with particular asthma phenotypes.; Il reste difficile actuellement de distinguer a priori les différents phénotypes d’asthme du nourrisson, et notamment de distinguer l’asthme à risque de persistance et de sévérité de l’asthme transitoire. Il est essentiel d’améliorer la prédiction du pronostic de l’asthme au cours de l’enfance, car l’asthme à début précoce concerne une proportion non négligeable, environ 10 %, de la population générale pédiatrique. L’épithélium pulmonaire sécrète différentes protéines, dont certaines, appelées pneumoprotéines, sont dorénavant dosables dans le sérum. Certaines d’entre elles pourraient constituer une piste intéressante dans la recherche de biomarqueurs associés aux phénotypes de l’asthme.

This review summarizes the available data related to the effects of air pollution on pollen grains from different plant species. Several studies carried out either onin situharvested pollen or on pollen exposed in different places more or less polluted are presented and discussed. The different experimental procedures used to monitor the impact of pollution on pollen grains and on various produced external or internal subparticles are listed. Physicochemical and biological effects of artificial pollution (gaseous and particulate) on pollen from different plants, in different laboratory conditions, are considered. The effects of polluted pollen grains, subparticles, and derived aeroallergens in animal models, inin vitrocell culture, on healthy human and allergic patients are described. Combined effects of atmospheric pollutants and pollen grains-derived biological material on allergic population are specifically discussed. Within the notion of “polluen,” some methodological biases are underlined and research tracks in this field are proposed.