Epidemiology of birch-pollen associated and primary hazelnut allergy in school-aged children of a Berlin birth cohort

Einleitung: Bei pollenassoziierter Haselnussallergie treten aufgrund einer Kreuzreak-tivität mit Birkenpollen meist orale Symptome auf; Betroffene vertragen geröstete Ha-selnuss. Eine primäre Haselnussallergie, die oft mit anaphylaktischen Reaktionen einhergeht, ist mit Immunglobulin E- Antikörpern gegen das hitzestabile Haselnuss-speicherprotein Cor a 14 assoziiert. Die Studienlage zur Prävalenz von Haselnussallergie ist heterogen. Birkenpollenallergie ist in Deutschland endemisch, im Zusammenhang mit Haselnussreaktionen bei Kindern lagen bisher keine Daten vor. Zielsetzung: Die vorliegende Arbeit untersuchte prospektiv und populationsbasiert die Prävalenzen und Zusammenhänge von allergischen Symptomen gegen Haselnuss und Birkenpollen sowie Sensibilisierung gegen diese Allergene bei Grundschulkin-dern. Methodik: In Berlin wurden von 2014-2017 alle der 1.570 für eine Geburtskohorten-studie rekrutierten Neugeborenen mit einem elterlichen Fragebogen für das Grund-schulalter nachverfolgt. Zusätzlich wurden standardisiert klinische Evaluationen, Hautpricktests, Serumanalysen auf Allergen-spezifisches Immunglobulin E und dop-pelblinde, plazebokontrollierte Nahrungsmittelprovokationen durchgeführt. Ergebnisse: Fast zwei Drittel der Geburtskohorte (n=1.004; 48% weiblich) konnten für die Nacherhebung gewonnen werden. Die Auswertung der Fragebögen ergab bei 1,9% der Kinder Symptome einer Haselnussallergie, bei 11,6% Symptome einer Bir-kenpollenallergie und bei 0,6% Symptome für beide Allergien. In einer Subgruppe von 261 Kindern, die auf eine allergische Sensibilisierung gegen Haselnuss und Birkenpollen untersucht wurde, waren 17,6% gegen Haselnuss sensi-bilisiert, nur wenige davon berichteten über Symptome. Eine Sensibilisierung gegen Birkenpollen fand sich bei 19,2% und gegen beide Allergene bei 16,1% der Kinder. Spezifisches Immunglobulin E im Serum gegen Cor a 14 war bei 4 Kindern (1,8%) po-sitiv. Nahrungsmittelprovokationen waren bei 11 Kindern indiziert und bei einem von 2 Kin-dern positiv. Die Eltern von 9 Kindern lehnten die Provokationstests ab. Schlussfolgerung: Eine Sensibilisierung gegen Haselnuss und Birkenpollen war in dieser Berliner Studienpopulation häufig, meist aber nicht mit Symptomen assoziiert. Die Größe der Geburtskohorte, die hohe Teilnahmerate am Follow-Up sowie der hohe Standardisierungsgrad der Methoden zählen zu den Stärken der Arbeit. Jedoch müss-ten weitere prospektive Bevölkerungsstudien aus unterschiedlichen und auch ländli-chen Regionen durchgeführt werden. Zur Diagnose einer Haselnussallergie ist das alleinige Vorliegen einer Sensibilisierung kein guter Parameter. Das klinische Bild, Kosensibilisierung gegen Birkenpollen, Komponentendiagnosik gegen Cor a 14 und doppelblinde, plazebokontrollierte Nahrungsmittelprovokationstests sind hierfür geeig-neter, auch wenn Eltern letzteren nicht immer zustimmen. Somit kann diese Arbeit da-zu beitragen, zukünftige Fehldiagnosen von Allergien und konsekutive Lebensqualitätseinschränkungen zu verhindern.Background: Due to cross reactivity with birch-pollen, pollen associated hazelnut al-lergy mostly causes oral symptoms and patients tolerate roasted hazelnut. Primary ha-zelnut allergy, which often causes anaphylactic reactions, is associated with immuno-globulin E antibodies targeted against Cor a 14, a heat stable hazelnut seed storage protein. The prevalence of hazelnut allergy reported by existing studies is heterogene-ous. Birch-pollen allergy is endemic in Germany, however so far there was no pub-lished data about the correlation with hazelnut reactions in children. Aims: The present analysis investigated the prevalence and correlation of allergic symptoms against hazelnut and birch-pollen prospectively, and population based as well as sensitization to these allergens in primary school aged children. Methods: From 2014-2017, a follow-up study of a birth cohort including 1,570 new-borns was conducted in Berlin by means of a parental online questionnaire for primary school age. Additionally, we conducted clinical evaluations, analysis of serum specific immunoglobulin E, and double-blind placebo-controlled food challenges according to a standardized protocol. Results: Almost two thirds of the birth cohort (n=1,004; 48% female) could be included in the follow-up. According to the parental questionnaire, 1.9% of children reported symptoms of hazelnut allergy, 11.6% symptoms of birch-pollen allergy and 0.6% symp-toms of both allergies. In a subgroup of 261 children who were tested for allergic sensitization against hazel-nut and birch-pollen 17.6% were sensitized to hazelnut. Only few of these children reported symptoms. 19.2% of children were sensitized to birch-pollen and 16.1% of children were sensitized to both allergens. Serum specific immunoglobulin E targeted against Cor a 14 was positive in 4 children (1.8%). Double-blind placebo-controlled food challenges were indicated in 11 children and positive in one out of 2 children. Parents of 9 children refused food challenge tests. Conclusion: Sensitization to hazelnut and birch-pollen was common in the Berlin population of this study. In most sensitized children no symptoms occurred. The size of the study population, the high response-rate of the follow-up as well as the highly standardized study protocol are strengths of this dissertation. Anyhow, more prospec-tive population studies from different settings including rural areas are needed. Sensi-tization to hazelnut is not adequate as a sole parameter to diagnose hazelnut allergy. Clinical symptoms, co-sensitization to birch-pollen, measurement of serum specific immunoglobulin E targeted against Cor a 14, and double-blind placebo-controlled food challenges give a better picture, although parents do not always agree to the latter one. Hereby, this paper can help prevent over-diagnosis of hazelnut allergy

Serotonin-specific neurons differentiated from human iPSCs form distinct subtypes with synaptic protein assembly

Human induced pluripotent stem cells (hiPSCs) have revolutionized the generation of experimental disease models, but the development of protocols for the differentiation of functionally active neuronal subtypes with defined specification is still in its infancy. While dysfunction of the brain serotonin (5-HT) system has been implicated in the etiology of various neuropsychiatric disorders, investigation of functional human 5-HT specific neurons in vitro has been restricted by technical limitations. We describe an efficient generation of functionally active neurons from hiPSCs displaying 5-HT specification by modification of a previously reported protocol. Furthermore, 5-HT specific neurons were characterized using high-end fluorescence imaging including super-resolution microscopy in combination with electrophysiological techniques. Differentiated hiPSCs synthesize 5-HT, express specific markers, such as tryptophan hydroxylase 2 and 5-HT transporter, and exhibit an electrophysiological signature characteristic of serotonergic neurons, with spontaneous rhythmic activities, broad action potentials and large afterhyperpolarization potentials. 5-HT specific neurons form synapses reflected by the expression of pre- and postsynaptic proteins, such as Bassoon and Homer. The distribution pattern of Bassoon, a marker of the active zone along the soma and extensions of neurons, indicates functionality via volume transmission. Among the high percentage of 5-HT specific neurons (~ 42%), a subpopulation of CDH13 + cells presumably designates dorsal raphe neurons. hiPSC-derived 5-HT specific neuronal cell cultures reflect the heterogeneous nature of dorsal and median raphe nuclei and may facilitate examining the association of serotonergic neuron subpopulations with neuropsychiatric disorders

Prevalence and early-life risk factors of school age allergic multimorbidity - the EuroPrevall-iFAAM birth cohort

BACKGROUND: Coexistenceofchildhoodasthma,eczemaandallergicrhinitisishigherthancanbeexpectedbychance,suggestingacommonmechanism.Dataonallergicmultimorbidityfromapan-European,population-basedbirthcohortstudyhasbeenlacking. This study compares the prevalence and early-life risk factors of these diseases in European primary school children.METHODS: IntheprospectivemulticentreobservationalEuroPrevall/iFAAMbirthcohortstudyweusedstandardizedquestionnairesonsocio-demographics,medicalhistory,parentalallergiesandlifestyle,andenvironmentalexposuresatbirth,12and24months.Atprimaryschoolage,parentsansweredISAAC-basedquestionsoncurrentasthma,rhinitisandeczema.Allergicmultimorbiditywasdefinedasthecoexistenceofatleasttwoofthese.RESULTS: From10,563childrenrecruitedatbirthin8studycentres,weincludeddatafrom5,572children(meanage8.2years;51.8%boys).Prevalenceestimateswere:asthma8.1%,allergicrhinitis13.3%,eczema12.0%.Allergicmultimorbiditywasseenin7.0%ofthewholecohort,rangingfrom1.2%(Athens,Greece)to10.9%(Madrid,Spain). Riskfactorsforallergicmultimorbidity, identified with AICc,includedfamily-allergy-score, oddsratio(OR)1.50 (95% CI 1.32-1.70)perstandarddeviation;early-lifeallergysymptoms, OR2.72 (2.34-3.16)foreachsymptom;andcaesareanbirth, OR1.35 (1.04-1.76).Femalegender, OR0.72 (0.58-0.90);oldersiblings,OR0.79 (0.63-0.99);andday-care, OR0.81 (0.63-1.06)wereprotectivefactors.CONCLUSION: AllergicmultimorbidityshouldberegardedasanimportantchronicchildhooddiseaseinEurope.Someoftheassociatedearly-lifefactorsaremodifiableandmaybeconsideredforpreventionstrategies.</p