Seasonal allergic rhinitis (SAR) is a disease caused by allergens from both environmental and genetic factors. Some researchers have studied the SAR based on traditional genetic methodologies. As technology develops, a new technique called single-cell RNA sequencing (scRNA-seq) is developed, which can generate high-dimension data. We apply two machine learning (ML) algorithms, random forest (RF) and partial least squares discriminant analysis (PLS-DA), for cell source classification and gene selection based on the SAR scRNA-seq time-series data from three allergic patients and four healthy controls denoised by single-cell variational inference (scVI). We additionally propose a new fitting method consisting of bootstrap and cubic smoothing splines to fit the averaged gene expressions per cell from different populations. To sum up, we find that both RF and PLS-DA could provide high classification accuracy, and RF is more preferable, considering its stable performance and strong gene-selection ability. Based on our analysis, there are 10 genes having discriminatory power to classify cells of allergic patients and healthy controls at any timepoints. Although there is no literature founded to show the direct connections between such 10 genes and SAR, the potential associations are indirectly confirmed by some studies. It shows a possibility that we can alarm allergic patients before a disease outbreak based on their genetic information. Meanwhile, our experiment results indicate that ML algorithms may discover something between genes and SAR compared with traditional techniques, which needs to be analyzed in genetics in the future.

<p>Kontaktna senzibilizacija, kao stanje specifične reaktivnosti kože, može biti egzogeni pokretač psorijaze. Rezultat je interakcije endogenih i egzogenih činioca. Jedan od najznačajnijih endogenih faktora kome se pripisuje uloga faktora rizika jeste pol. Cilj istraživanja bio je da se kod obolelih od psorijaze utvrdi učestalost i distribucija kontaktne senzibilizacije u odnosu na pol, razlike u distribuciji kontaktne senzibilizacije po polu&nbsp; između osoba obolelih od psorijaze i osoba pod sumnjom na postojanje kontaktnog alergijskog dermatitisa, povezanost kontaktne senzibilizacije i težine kliničkog nalaza i povezanost kontaktne senzibilizacije i dužine trajanja oboljenja. Hipoteza istraživanja polazila je od pretpostavke da je kontaktni alergijski dermatitis redak kod obolelih od psorijaze, jer hronična inflamacija u koži smanjuje njenu sposobnost specifične senzibilizacije a da je veća učestalost kontaktne senzibilizacije kod osoba ženskog pola rezultat egzogenog faktora tj.ekspozicije, kao i da je učestalost kontaktne senzibilizacije u pozitivnoj korelaciji sa težinom i dužinom trajanja oboljenja. Istaživanje je sprovedeno kod 176 ispitanika koji su bili podeljeni u dve grupe. Eksperimentalnu grupu su činili oboleli od psorijaze, a kontrolnu grupu ispitanici upućeni na alergolo&scaron;ko testiranje pod sumnjom na postojanje kontaktnog alergijskog dermatitisa. Obolelima od psorijaze je ocenjivana težine oboljenja PASI skorom, a svi ispitanici bili su alergolo&scaron;ki testirani epikutanim -pač testom. Pozitivni rezultati alergolo&scaron;kog testiranja su analizirani, u cilju utvrđivanja kliničke relevantnosti istih. Ispitanicima u grupi obolelih od psorijaze je testom skarifikacije određivano prisustvo ili odsustvo Koebnerovog izomorfnog podražajnog fenomena. Istraživanjem je utvrđeno, da se kontaktno reagovanje kod obolelih od psorijaze na najmanje jedan standardni alergen nije statistički značajno razlikovalo od reagovanja osoba kod kojih je postavljena sumnja na postojanje kontaktnog alergijskog dermatitisa, ali je senzitivnost izražena kroz prosečan broj pozitivnih testova po jednom ispitaniku bila statistički značajno niža kod obolelih od psorijaze. Poređenjem kontaktnog reagovanja mu&scaron;karaca i žena nisu utvrđene značajna razlike u reagovanju u odnosu na pol. Težina oboljenja nije uticala na učestalost kontaktne senzibilizacije kod obolelih od psorijaze, ali je učestalost kontaktne senzibilizacije bila u pozitivnoj korelaciji sa dužinom trajanja bolesti. Niža stopa kontaktnog reagovanja utvrđena je kod osoba obolelih od psorijaze koji su imali pozitivan Koebnerov fenomen u trenutku ispitivanja.</p> / <p>Contact sensitization as a state of specific skin reactivity may provoke psoriasis resulting from an interaction between extrinsic and intrinsic factors. One of the most significant factors characterized, as a risk factor, is the sex. The aim of this study was to determinate the frequency and distribution of contact sensitization in patients with&nbsp; psoriasis with respect to their sex, as well as the differences in the distribution of contact sensitization in both sexes, namely&nbsp; with patients with psoriasis and patients&nbsp; suspected to allergic contact dermatitis. Consequently, appropriate attention was paid to the correlation between contact sensitization and disease severity, and between contact sensitization and disease duration. Hypothesis were based on the assumption that allergic contact dermatitis is rare in&nbsp; patients with psoriasis, as a chronic inflammation of the skin reduces its ability specific sensitization, as well as that the higher frequency of contact sensitization in females represent a result of exogenous factors, i.e. exposition, and finally that there is a positive correlation between the incidence of contact sensitization and the disease severity, and contact sensitization and the disease duration. The study included 176 patients. They were divided into two groups: the study group included patients with psoriasis, while the control group included patients referred for allergy testing, since they were suspected to allergic contact dermatitis. The severity of psoriasis was evaluated by PASI score. Thereafter,&nbsp; each patient underwent patch testing. The positive results of patch tests were evaluated with the aim to define their clinical relevancy. Subjects from the group of psoriatic patients passed scarification test carried out to indicate the presence or absence of K&ouml;ebner isomorphic phenomenon. This research led us to the conclusion that the positive reaction of psoriatic patients to at least one standard allergen did not indicate a statistically significant different reaction when compared to the reaction of patients suspected to allergic contact dermatitis. From the other side, the sensitivity expressed through the average number of positive&nbsp; tests per one&nbsp; tested&nbsp; patients was&nbsp; significantly lower in&nbsp; patients&nbsp; with psoriasis. Comparison of the contact response of men and women showed no significant differences in response with respect to&nbsp; their sex. The&nbsp; disease severity did not influence the frequency of contact sensitization in patients&nbsp; with&nbsp; psoriasis. At&nbsp; the same time, the frequency of contact sensitization stood in a positive correlation with the duration of disease. The lower rate of contact sensitization was found in patients with psoriasis who have had a&nbsp; positive K&ouml;ebner phenomenon at&nbsp; the time of testing.</p>

Objective: Allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP) are of high importance in otorhinolaryngology. Some of their symptoms are related to changes in the nasal trigeminal sensitivity. The aim of this study was to compare nasal trigeminal sensitivity in patients with AR, CRSwNP, and healthy controls (HC). - Methods: A total of 75 individuals participated (age 19–78 years; 34 AR, 10 CRSwNP and 31 HC). Olfactory function was determined using the extended Sniffin’ Sticks test battery. Trigeminal sensitivity was assessed with CO₂ detection thresholds.Trigeminal negative mucosal potentials (NMP) and EEG-derived event-related potentials (ERP) were recorded in response to selective olfactory (phenylethyl alcohol) and trigeminal (CO₂) stimuli using high-precision air-dilution olfactometry. - Results: In comparison to HC, AR patients had lower CO₂ thresholds, also reflected in shorter peak latencies in NMP and trigeminal ERP measurements. CRSwNP patients had a decreased sensitivity for trigeminal stimuli, also reflected in prolonged trigeminal ERP latencies, and reduced olfactory function compared to HC. - Conclusion: AR patients seemed to be more sensitive to trigeminal stimuli than CRSwNP patients. Importantly, the differences could be shown on psychophysical and electrophysiological levels. The changes in trigeminal sensitivity appear to be present already at the level of the respiratory epithelium. The differences between the two groups may depend on the specific inflammatory changes accompanying each disorder, the degree of inflammatory activity, or duration of the inflammatory disorder. However, because the sample sizes are relatively small, these results need to be confirmed in the future studies with larger groups.

No description available.

Oral lichen planus (OLP) är en idiopatisk kronisk inflammatorisk sjukdom som drabbar munslemhinnan hos ca 2 % av den svenska befolkningen. Amalgamfyllningar kan framkalla lichenoida kontaktlesioner (cOLL), som kliniskt kan vara svåra att särskilja från OLP. Det är dessutom inte möjligt att skilja mellan OLP och cOLL histologiskt. Det är viktigt att kunna särskilja OLP och cOLL då behandlingen av dem skiljer sig.Toll-like receptorer (TLR) finns på flera av kroppens celler. De är en del av det medfödda immunförsvaret men de har också kopplats till autoimmuna sjuksomar. En ökad förekomst av TLR i skivepitel har påvisats vid OLP.Syftet med denna studie är att undersöka variationer i uttrycket av TLR4 och TLR9 i OLP och cOLL. Vår hypotes är att en histologisk skillnad i OLP och cOLL ska kunna observeras p.g.a. skillnader i patogenesen mellan OLP och cOLL.Metod: Vävnadsprov med histologiskt verifierad lichenoid reaktion valdes från Biobanken, Oral Patologi, Malmö från patienter med de kliniskt ställda diagnoserna OLP (10) och cOLL (12). TLR4 och TLR9 identifierades med hjälp av immunhistokemisk färgning varefter reaktionens lokalisation och intensitet jämfördes mellan de två grupperna.Resultat: En signifikant skillnad observerades i infärgningen av TLR4 hos fibroblaster, lymfocyter och makrofager, där TLR4 var mer positiv i cOLL. Uttrycket av TLR9 hos lymfocyter var starkare vid OLP än cOLL.Slutsats: Våra resultat visade att det finns en skillnad i uttrycket av TLR4 och TLR9 i cOLL och OLP. Resultaten bekräftar att OLP och cOLL har olika patogenes, men ytterligare studier behövs för att klargöra hur. / Oral lichen planus (OLP) is an idiopathic chronic inflammatory disease that affects the oral mucosa in approximately 2% of the Swedish population. Amalgam fillings may induce contact oral lichenoid lesions (cOLL) that can be difficult to clinically distinguish from OLP. It is not possible to histologically distinguish between OLP and cOLL. As their treatments differ, the correct diagnosis is vital.Toll-like receptors (TLR) are expressed by most of the body's cells and are part of the innate immune system, however they have also been linked to certain autoimmune diseases. OLP exhibits an increased amount of TLR in the epithelium.The purpose of this study is to investigate the variations in the expression of TLR4 and TLR9 in OLP and cOLL. Our hypothesis is that a histological difference in OLP and cOLL can be observed due to TLRs different roles in maintaining the immune response.Method: Tissue samples with histologically confirmed lichenoid reactions were chosen from Biobank, Oral Pathology, Malmö, from patients with the clinical diagnosis OLP (10 subjects) and cOLL (12 subjects). TLR4 and TLR9 were identified by immunohistochemical staining and compared between the two groups.Results: A significant difference was observed in TLR4 staining of fibroblasts, lymphocytes and macrophages where the antibody was less expressive in OLP. In TLR9 staining lymphocytes were stronger expressed in OLP compared to cOLL.Conclusion: Our results showed that there was a difference in the expression of TLR4 and TLR9 in cOLL and OLP, this could be a result of OLP being an autoimmune disorder. Further studies on this subject are recommended on this subject.

Abstract There are eight foods that contribute to food allergies in the western world and peanut is the most common. Currently, there are no medical treatments that can cure an individual of food allergy, so avoidance of the allergic food is the only option. In the United States, there are three immunodominant allergic proteins accountable for patient sensitization to peanut, Arachis hypogea 1, 2, and 3 (Ara h 1, Ara h 2, Ara h 3). Therefore, research into why peanuts are more allergic than other foods that have homologous proteins is critical and may be obtained by studying the structural and allergenic properties of individual allergens and the changes that occur due to food processing. In this study, the basic and acidic subunits of Ara h 3 were cloned, expressed, and purified, and compared with each other and with the native Ara h 3 purified from peanut for differences in binding to IgE from peanut allergic individuals. Also, an in vitro Maillard reaction was performed on purified native raw Ara h 3 and patient serum IgE western blots were performed. This study concluded that an in vitro Maillard reaction enhanced IgE binding to Ara h 3, IgE binding to native Ara h 3 was in most cases higher than to the recombinant Ara h 3 subunits, and recognition of the acidic subunit was much higher than the and basic subunits in both the recombinant and native forms of the protein were investigated. Keywords:

Allergy, as one of the worldwide most frequent pathologies, belongs to illnesses with constantly growing incidence among young children. In genetically predisposed individuals, dendritic cells are able to polarize the immune response of Th2 in contact with the allergen. Postnatal probiotic supplementation could be one the preventive measure to prevent the development of allergic diseases. It has been shown that introduction of selected probiotic strains or mixtures can prevent development of allergy. In this diploma thesis, the capacity of probiotic strain Escherichia coli O83:K24:H31 (E. coli O83) to support maturation of dendritic cells (DC) and polarization of immune responses was tested. Introduction of this probiotic vaccine called Colinfant Newborn appears to be suitable preventive measure, lowering allergy incidence in children with predisposition to development of allergy. The aim of this diploma thesis was to observe capacity of E. coli O83 to support maturation of the two main subpopulations of dendritic cells (myeloid dendritic cells - mDC and plasmacytoid dendritic cells - pDC) in cord blood of newborns of healthy mothers (children with relatively low risk for allergy development) and allergic mothers (children with relatively high risk for allergy development). To achieve this goal,...

Allergy as one of the most frequent pathologies worldwide belongs to illnesses with constantly increasing incidence even amongst young children. It develops in genetically predisposed individuals whose dendritic cells (DC) are, after contact with allergen, able to polarize the immune response predominantly to Th2, while Th1 response is supressed. One of the possible preventive measures to avoid an allergic disease developement could be an early postnatal supplementation of chosen probiotic bacterial strains or their mixtures. One of them is a well characterized strain Escherichia coli O83:K24:H31 (E. coli O83). Administering of this probiotic vaccine called Colifant Newborn is showing to be an effective prophylaxis to decrese the incidence of allergies in children with predisposition to their developement. The aim of my diploma thesis was to experimentally confirm the capacity of E. coli O83 to support maturation of two main subpopulations of newborn DC available from cord blood: myeloid dentritic cells - mDC and plasmacytoid dentritic cells - pDC. This DC subpopulations were isolated from cord blood of children born to healthy (non-allergic) mothers who had a low risk of allergy development or from children of allergic mothers who had an increased risk of allergy development. Subsequently, after...

A asma ocupacional é a forma mais comum de doença pulmonar relacionada ao trabalho e vários dos casos reportados estão correlacionados à exposição de proteases. A serino protease subtilisina foi bastante utilizada na década de 60 e foi a principal responsável pela alta incidência de asma na indústria de detergente. Este projeto visou a desenvolver um modelo murino de inflamação alérgica pulmonar à subtilisina e caracterizar os mecanismos principais envolvidos nessa resposta. A sensibilização e desafio com subtilisina induziu doença alérgica pulmonar, verificada pela eosinofilia às vias aéreas, produção de muco, IgE total, hiper reatividade brônquica e produção de citocinas tipo II no pulmão. Estas respostas foram dependentes da atividade enzimática da subtilisina, PAR-2, receptor de IL-33 ST2, IL-1R e da sinalização via MyD88. Em conjunto, nossos resultados estabelecem um novo modelo experimental de asma ocupacional induzida por subtilisina e fornece os principais mecanismos moleculares responsáveis pela inflamação alérgica. / Occupational asthma is the most common form of pulmonary disease related to work. Most of occupational asthma cases reported are strictly correlated with proteases exposure. Serine protease subtilisin was widely used in the detergent industry during the 60s, which resulted in increased incidence of occupational asthma. We aimed to develop and characterize a murine model of occupational asthma using subtilisin as allergen. Briefly, sensitization and challenge with subtilisin triggered lung allergic inflammation, as accessed by eosinophilic influx to the airways, mucus production, and increased levels of type II cytokines. Subtilisin induced total IgE and airway hyperactivity. Allergic responses to subtilisin were dependent on its serine protease activity, protease-activated receptor (PAR)-2, IL-33 receptor ST2, IL-1R, and Myd88 signaling. Together, these data establish a new murine model of occupational asthma induced by subtilisin and provide the main molecular mechanisms responsible for allergic inflammation.

Objectifs L'objectif de la thèse est de caractériser par PCR quantitative en temps réel (QPCR) l'environnement fongique, bactérien ainsi que l'exposition à d'autres organismes allergisants (acariens et animaux de compagnie). Cette caractérisation des logements a pour but de mieux comprendre les interactions entre les différents micro-organismes de l'environnement intérieur et leurs relations aux maladies allergiques, dans le cadre d'une étude de grande cohorte. L'objectif secondaire est la mise en place de nouvelles QPCR dans d'autres circonstances sanitaires (infections, PHS) afin de mieux caractériser l'impact des microorganismes de l'environnement. L'étude EBRA-ELFE L'étude ELFE incluant 18 319 enfants est la première cohorte française qui s'intéresse au développement des enfants de la naissance à leur majorité dans une approche multi­disciplinaire. Une étude nichée EBRA (Environnement microBiologique et Risque Allergique) est centrée sur l'étude microbiologique des poussières dans les chambres d'enfant. Le mode d'échantillonnage (par capteur électrostatique à poussière, EDC) et d'analyse (QPCR) ont été validés et optimisés pour garantir l'acceptabilité du dispositif et la qualité des quantifications. Un panel de 10 cibles (moisissures, acariens, bactéries) sélectionnées pour leur caractère allergisant, toxique, infectieux ou potentiellement protecteur vis-à-vis des maladies allergiques a été initialement utilisé. Ainsi lors de la première collecte à la naissance des enfants en 2011, 3217 CEP ont été quantifiés par QPCR. Les concentrations de six moisissures (Aspergillus fumigatus, Aspergillus versicolor, Alternaria alternata, Cladosporium sphaerospermum, Penicillium chrysogenum, Stachybotrys chartarum), trois groupes de bactéries (Enterobacteriaceae, Mycobacteria et Streptomyces) et un acarien (Dermatophagoïdes pteronissynus) de l'environnement immédiat du nouveau-né ont été obtenues. Ces données ont permis d'identifier six profils de logements différents avec un gradient géographique E-O recouvrant la distribution des sifflements de l'asthme en France. Un deuxième panel de 10 cibles a été choisi et documenté. Il inclut entre autres des cibles « chien » et « chat » pour proposer un test complet comprenant les allergènes principaux des logements. La collaboration avec le groupe ELFE continue et un projet pour une deuxième campagne d'échantillonnage à 5 ans se met en place. L'utilisation de la QPCR pour caractériser d'autres situations à risque. La QPCR est un outil de quantification standardisé et reproductible et ses applications sont multiples. Au cours de ce travail de thèse, elle a été utilisée pour caractériser d'autres situations à risque : quantifier la présence de Thermoactinomyces vulgaris dans les aérosols des stations de compostages, détecter la présence d'Aspergillus fumigatus dans des environnements pouvant recevoir des patients immunodéprimés, mettre en évidence la présence d'ADN d' Aspergillus fumigatus ou de mucorales dans le sérum de patients immunodéprimés. Conclusion Les outils développés et les résultats obtenus pendant la thèse représentent une avancée pour une meilleure connaissance du monde microbien qui nous entoure et contribueront à mieux comprendre les mécanismes de développement des maladies allergiques / Objectives The aim of the study is to characterize by quantitative real-time PCR (QPCR) fungal, bacterial environment as well as exposure to other allergenic organisms (mites and pets). This characterization of dwellings aims to better understand the interactions between the different micro-organisms of the indoor environment and their relation to allergie diseases. The secondary aim is the use of other QPCRs in other health circumstances (infections, ABPA) te better characterize the impact of environmental microorganisms. The EBRA-ELFE study The ELFE study, which includes 18,319 children, is the first French cohort to study the development of children from birth to majority in a multi-disciplinary approach. A nested study EBRA (MicroBiological Environment and Allergie Risk) focuses on the microbiological compositior of dust in children's rooms. The electrostatic dust collector (EDC) sampling and analysis mode has been validated to guarantee an acceptable system (in terms of cost and constraints for the participants) and to optimize the quality of QPCR quantification. A panel of 10 targets (molds, mites, bacteria) selected for their allergenic, taxie, infectious or potentially protective effect against allergie diseases was initially used. Thus during the first sampling at birth of children in 2011, 3217 EDC were quantified by QPCR. The concentrations of six molds (Aspergillus fumigatus, Aspergillus versicolor, Alternaria alternata, Cladosporium sphaerospermum, Penicillium chrysogenum, Stachybotrys chartarum), three groups of bacteria (Enterobacteriaceae, Mycobacteria and Streptomyces) and one mite (Dermatophagoides pteronissynus) of the immediate environment of the new have been obtained. These data made it possible to identify six different dwelling profiles A second panel of 10 targets was chosen and documented. It includes "dog" and "cat" targets te propose a complete test including the main allergens of the dwellings. The collaboration with thE ELFE group continues and a project for a second 5-year sampling campaign is set up.The use of QPCR for the use of QPCR other risk situations The QPCR is a standardized tool, reproducible, allowing quantification and its applications are multiple. During this work, it was used to characterize other risk situations: presence of Thermoactinomyces vulgaris in the aerosols of composting stations, presence of Aspergillus fumigatus in environments that could receive immunocompromised patients , the presence of Aspergillus fumigatus DNA or mucorales in the serum of immunocompromised patients. Conclusion Tools developed and the results obtained during the study represent a step forward for a better knowledge of the microbial envrionnement and will contribute to a better understanding of the mechanisms of development of allergie diseases