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Dynamics of Gut Microbiota According to the Delivery Mode in Healthy Korean Infants.

Eun LEE ; Byoung Ju KIM ; Mi Jin KANG ; Kil Yong CHOI ; Hyun Ju CHO ; Yeongho KIM ; Song I YANG ; Young Ho JUNG ; Hyung Young KIM ; Ju Hee SEO ; Ji Won KWON ; Hyo Bin KIM ; So Yeon LEE ; Soo Jong HONG

Allergy, Asthma & Immunology Research.2016;8(5):471-477. doi:10.4168/aair.2016.8.5.471

Microbial colonization of the infant gut is unstable and shows a wide range of diversity between individuals. Gut microbiota play an important role in the development of the immune system, and an imbalance in these organisms can affect health, including an increased risk of allergic diseases. Microbial colonization of young infants is affected by the delivery mode at birth and the consequent alterations of gut microbiota in early life affect the development of allergic diseases. We investigated the effects of the delivery mode on the temporal dynamics of gut microbiota in healthy Korean infants. Fecal samples were collected at 1-3 days, 1 month, and 6 months after birth in six healthy infants. Microbiota were characterized by 16S rRNA shotgun sequencing. At the first and third days of life, infants born by vaginal delivery showed a higher richness and diversity of gut microbiota compared with those born by cesarean section. However, these differences disappeared with age. The Bacteroides genus and Bacteroidetes phylum were abundant in infants born by vaginal delivery, whereas Bacilli and Clostridium g4 were increased in infants born by cesarean section. The Firmicutes phylum and Bacteroides genus showed convergent dynamics with age. This study demonstrated the effect of delivery mode on the dynamics of gut microbiota profiles in healthy Korean infants.
Bacteroides ; Bacteroidetes ; Cesarean Section ; Clostridium ; Colon ; Female ; Firmicutes ; Gastrointestinal Microbiome* ; Humans ; Immune System ; Infant* ; Microbiota ; Parturition ; Pregnancy

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Genes Involved in Interleukin-1 Receptor Type II Activities Are Associated With Asthmatic Phenotypes.

Anne Marie MADORE ; Vanessa T VAILLANCOURT ; Emmanuelle BOUZIGON ; Chloé SARNOWSKI ; Florent MONIER ; Marie Hélène DIZIER ; Florence DEMENAIS ; Catherine LAPRISE

Allergy, Asthma & Immunology Research.2016;8(5):466-470. doi:10.4168/aair.2016.8.5.466

PURPOSE: Interleukin-1 (IL-1) plays a key role in inflammation and immunity and its decoy receptor, IL-1R2, has been implicated in transcriptomic and genetic studies of asthma. METHODS: Two large asthma family collections, the French-Canadian Saguenay-Lac-St-Jean (SLSJ) study and the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA), were used to investigate the association of SNPs in 10 genes that modulate IL-1R2 activities with asthma, allergic asthma, and atopy. Gene-gene interactions were also tested. RESULTS: One SNP in BACE2 was associated with allergic asthma in the SLSJ study and replicated in the EGEA study before statistical correction for multiple testing. Additionally, two SNPs in the MMP2 gene were replicated in both studies prior to statistical correction and reached significance in the combined analysis. Moreover, three gene-gene interactions also survived statistical correction in the combined analyses (BACE1-IL1RAP in asthma and allergic asthma and IL1R1-IL1RAP in atopy). CONCLUSIONS: Our results highlight the relevance of genes involved in the IL-1R2 activity in the context of asthma and asthma-related traits.
Asthma ; Epidemiologic Studies ; Genetics ; Humans ; Inflammation ; Interleukin-1* ; Phenotype* ; Polymorphism, Single Nucleotide ; Receptors, Interleukin-1 Type II*

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Soluble CD93 as a Novel Biomarker in Asthma Exacerbation.

Naseh SIGARI ; Ali JALILI ; Laili MAHDAWI ; Ebrahim GHADERI ; Mohammadi SHILAN

Allergy, Asthma & Immunology Research.2016;8(5):461-465. doi:10.4168/aair.2016.8.5.461

Asthma research is shifting from studying symptoms and lung functions to the narrow-focus cellular profiles protein analysis, biomarkers, and genetic markers. The transmembrane glycoprotein CD93 is involved in endothelial cell migration, angiogenesis, leukocytes extravasation, apoptosis, innate immunity and inflammation. Relationships between the serum level of soluble CD93 (sCD93) and acute myocardial infarction/premature MI/inflammatory arthritis/skin sclerosis have recently been reported. We hypothesized that sCD93 would be elevated during the acute phase of asthma. We measured the serum level of sCD93 in 57 patients with asthma exacerbation and 57 age-and gender-matched healthy controls. Additionally, sCD93 was reassessed at the time of discharge from the hospital. Clinical characteristics and peak expiratory flow (PEF) of the patients were assessed. The primary outcome was the comparison of serum level of sCD93 between asthmatics and healthy subjects. The sCD93 values ranged from 128 to 789 ng/mL in asthmatics (345.83±115.81) and from 31 to 289 ng/mL in control subjects (169.46±62.43). The difference between the 2 groups was statistically significant (P<0.001). The association between sCD93 and asthma remained significant after adjusting for age, sex, and BMI. The differences between asthmatics and controls remained significant on the last day of hospital stay. The association between sCD93 and PEF was not significant. In conclusion, the serum level of soluble CD93 is increased in patients with asthma exacerbation. It also showed that serum levels of sCD93 decreased with treatment of asthma attack. The clinical usefulness of determination of sCD93 as a biomarker of asthma requires further studies.
Apoptosis ; Asthma* ; Biomarkers ; Endothelial Cells ; Genetic Markers ; Glycoproteins ; Healthy Volunteers ; Humans ; Immunity, Innate ; Inflammation ; Length of Stay ; Leukocytes ; Lung ; Sclerosis

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Periostin and Interleukin-13 Are Independently Related to Chronic Spontaneous Urticaria.

Youin BAE ; Kenji IZUHARA ; Soichiro OHTA ; Junya ONO ; Gwan Ui HONG ; Jai Youl RO ; Gyeong Hun PARK ; Jeong Hee CHOI

Allergy, Asthma & Immunology Research.2016;8(5):457-460. doi:10.4168/aair.2016.8.5.457

Chronic spontaneous urticaria (CSU) is a complex idiopathic disease of the skin with various cellular infiltrations. Although mast cells are key effector cells in the pathogenesis of CSU, CD4+ T helper 2 cells also have particular roles in the development and maintenance of CSU. Periostin is known as a downstream molecule of interleukin (IL)-4 and IL-13, key cytokines of type 2 immune responses. In this study, we examined periostin and IL-13 levels in the sera of patients with CSU (n=84) and healthy normal controls (NCs, n=43). Periostin levels were significantly lower in the CSU group than in NCs (71.4±21.8 vs 85.1±22.4 ng/mL, P=0.04). Periostin levels were also lower in the severe CSU group than those in mild CSU (59.7±18.0 vs 73.4±22.0 ng/mL, P=0.04). However, IL-13 levels were significantly higher in patients with CSU than in NCs (508.5±51.2 vs 200.7±13.3 pg/mL, P=0.001). In conclusion, periostin and IL-13 may be independently related to the pathogenesis of CSU.
Cytokines ; Humans ; Interleukin-13* ; Interleukins ; Mast Cells ; Skin ; Urticaria*

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Synergistic Effect of Dermatophagoides farinae and Lipopolysaccharides in Human Middle ear Epithelial Cells.

Ji Eun LEE ; Yeon Hoo KIM ; Chae Seo RHEE ; Dong Young KIM

Allergy, Asthma & Immunology Research.2016;8(5):445-456. doi:10.4168/aair.2016.8.5.445

PURPOSE: Although the concept of "one airway, one disease," which includes the middle ear space as part of the united airway is well recognized, the role of allergens in otitis media with effusion (OME) is not clearly understood. We aimed to investigate the effect of the interaction between Dermatophagoides farinae (Der f) and lipopolysaccharide (LPS) on the induction of epithelial inflammatory response in vitro. METHODS: Primary human middle ear epithelial cells were exposed to Der f, LPS, or both in different sequences, and the magnitude of the immunologic responses was compared. The mRNA expressiona of mucin (MUC) 4, 5AC, 5B, 8, GM-CSF, TNF-α, TLR4, and MD-2 were evaluated using real-time PCR. MUC levels before and after siRNA-mediated knockout of TLR4 and MD-2 were assessed. Lastly, the involved cell signaling pathway was evaluated. RESULTS: The expressiona of cytokines, and the MUC 4, 5AC, 5B, and 8 genes were augmented by pretreatment with Der f followed by LPS; however, reverse treatment or combined treatment did not induce the same magnitude of response. Increased MUC expression was decreased by TLR4 knockdown, but not by MD-2 knockdown. The signal intensity of MUC 8 was higher in MD-2 over-expressed cells than in those exposed to LPS only. The translocation of nuclear factor-κB was observed in cells pretreated with Der f followed by LPS. CONCLUSIONS: When Der f treatment preceded LPS exposure, Der f and LPS acted synergistically in the induction of pro-inflammatory cytokines and the MUC gene, suggesting an important role in the development of OME in patients with concealed allergy airway sensitization.
Allergens ; Cytokines ; Dermatophagoides farinae* ; Ear, Middle* ; Epithelial Cells* ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans* ; Hypersensitivity ; Immunity, Innate ; In Vitro Techniques ; Lipopolysaccharides* ; Mucins ; Otitis Media with Effusion ; Pyroglyphidae* ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Toll-Like Receptors

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Vacuolar Serine Protease Is a Major Allergen of Fusarium proliferatum and an IgE-Cross Reactive Pan-Fungal Allergen.

Chang Ching YEH ; Hsiao Yun TAI ; Hong CHOU ; Keh Gong WU ; Horng Der SHEN

Allergy, Asthma & Immunology Research.2016;8(5):438-444. doi:10.4168/aair.2016.8.5.438

PURPOSE: Fusarium species are among prevalent airborne fungi and causative agents of human respiratory atopic disorders. We previously identified a 36.5-kDa F. proliferatum component recognized by IgE antibodies in 9 (53%) of the 17 F. proliferatum-sensitized atopic serum samples. The purpose of this study is to characterize the 36.5-kDa allergen of F. proliferatum. METHODS: Characterization of allergens and determination of IgE cross-reactivity were performed by cDNA cloning/expression and immunoblot inhibition studies. RESULTS: Based on the finding that the 36.5-kDa IgE-binding component reacted with the mouse monoclonal antibody FUM20 against fungal vacuolar serine protease allergens, the cDNA of F. proliferatum vacuolar serine protease (Fus p 9.0101) was subsequently cloned. Nine serum samples from respiratory atopic patients with IgE binding to the vacuolar serine protease allergen of Penicillium chrysogenum (Pen ch 18) also showed IgE-immunoblot reactivity to rFus p 9.0101. The purified rFus p 9.0101 can inhibit IgE and FUM20 binding to the 36.5-kDa component of F. proliferatum. Thus, a novel and important Fus p 9.0101 was identified. The rPen ch 18 can inhibit IgE binding to Fus p 9.0101. It indicates that IgE cross-reactivity between Fus p 9.0101 and Pen ch 18 also exists. Furthermore, neither rFus p 9.0101 K88A nor rPen ch 18 K89A mutants inhibited IgE binding to rFus p 9.0101. Lys88 was considered a critical core amino acid in IgE binding to r Fus p 9.0101 and a residue responsible for IgE cross-reactivity between Fus p 9.0101 and Pen ch 18 allergens. CONCLUSIONS: Results obtained from this study indicate that vacuolar serine protease may be a major allergen of F. proliferatum and an important IgE cross-reactive pan-fungal allergen, and provide important bases for clinical diagnosis of fungal allergy.
Allergens ; Animals ; Antibodies ; Clone Cells ; Diagnosis ; DNA, Complementary ; Fungi ; Fusarium* ; Humans ; Hypersensitivity ; Immunoglobulin E ; Mice ; Penicillium chrysogenum ; Serine Proteases* ; Serine*

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Orthologous Allergens and Diagnostic Utility of Major Allergen Alt a 1.

Antonio MORENO ; Fernando PINEDA ; Javier ALCOVER ; David RODRÍGUEZ ; Ricardo PALACIOS ; Eduardo MARTÍNEZ-NAVES

Allergy, Asthma & Immunology Research.2016;8(5):428-437. doi:10.4168/aair.2016.8.5.428

PURPOSE: Hypersensitivity to fungi is associated with rhinoconjunctivitis and asthma. For some fungi, such as Alternaria alternata (A. alternata), the symptoms of asthma are persistent, increasing disease severity and the risk of fatal outcomes. There are a large number of species of fungi but knowledge of them remains limited. This, together with the difficulties in obtaining adequate standardized extracts, means that there remain significant challenges in the diagnosis and immunotherapy of allergy associated with fungi. The type of indoor fungi related to asthma/allergy varies according to geographic, climatic, and seasonal factors, making their study difficult. The aim of this study was to determine hypersensitivity to indoor fungi in a population from Cuenca, Spain. METHODS: Thirty-five patients with symptoms compatible with rhinitis or asthma who showed clear worsening of their symptoms in their homes or workplace were included. In vivo and in vitro tests were made with a battery of fungal allergens, including the species isolated in the home or workplace. RESULTS: Ulocladium botrytis (U. botrytis) and A. alternata were the most representative species as a source of home sensitization. These species showed very high concordance in skin tests, specific IgE, and histamine release. The allergen Alt a 1, which was recognized in all patients, was detected in A. alternata, U. botrytis, and Stemphylium botryosum (S. botryosum). CONCLUSIONS: U. botrytis and A. alternata were the most representative species as a source of home sensitization. Alt a 1 was recognized in all patients and may be considered a non-species-specific allergen that could be used as a diagnostic source of sensitization to some species of the Pleosporaceae family.
Allergens* ; Alternaria ; Asthma ; Botrytis ; Diagnosis ; Fatal Outcome ; Fungi ; Histamine Release ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunotherapy ; In Vitro Techniques ; Rhinitis ; Seasons ; Skin Tests ; Spain

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Systemic Reactions to Dust Mite Subcutaneous Immunotherapy: A 3-Year Follow-up Study.

Xiang DONG ; Nan HUANG ; Wenjing LI ; Lintao HU ; Xiaolong WANG ; Yin WANG ; Ning XIANG ; Guanghui LIU ; Rongfei ZHU

Allergy, Asthma & Immunology Research.2016;8(5):421-427. doi:10.4168/aair.2016.8.5.421

PURPOSE: The incidence of allergen specific immunotherapy-related systemic reactions (SRs) varies among different studies, and many factors are likely to contribute to SRs. This study aims to investigate the incidence, characteristics, and risk factors of SRs to standardize dust mite-specific subcutaneous immunotherapy (SCIT) in Central China. METHODS: All patients receiving standardized dust mites (100-100,000 SQ-U/mL; Alutard SQ, Hørsholn, Denmark) immunotherapy were followed up. Recorded data included demographics, diagnosis, patient status, pulmonary function testing results before and after each injection, allergen dosage, and details of SRs. RESULTS: From June 2011 to August 2014, a total of 208 patients received 4,369 injections; 27 (13.0%) patients experienced 48 (1.1%) systemic reactions. Most of the SRs were grade 2 reactions (n=30, 62.5%), followed by grade 1 (n=11, 22.9%), grade 3 (n=7, 14.6%), and no fatal reactions occurred. Forty-six SRs (95.8%) occurred within 30 minutes. Higher SR rates were associated with high concentration extracts (100,000 SQ-U/mL), injections with concomitant local reactions (LRs), children, asthma and high sensitivity (skin prick test 3+/4+ and/or sIgE≥17.5 kUA/L) (P<0.05). The estimated odds of SRs increased in children (OR=6.57; 95% CI: 1.88-22.97, P=0.003), asthmatic patients (OR=4.10; 95% CI: 1.72-9.80, P=0.002), and injections with LRs (OR=2.41; 95% CI: 1.33-4.36, P=0.004). CONCLUSIONS: The incidence of SRs to dust mite SCIT was low, and multiple factors were associated with the increased incidence of SRs. Children, asthmatics and patients with concomitant LR may be prone to develop SRs.
Asthma ; Child ; China ; Demography ; Dermatophagoides pteronyssinus ; Diagnosis ; Dust* ; Follow-Up Studies* ; Humans ; Immunotherapy* ; Incidence ; Mites* ; Respiratory Function Tests ; Risk Factors

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Short-, Intermediate-, and Long-Term Changes in Basophil Reactivity Induced by Venom Immunotherapy.

Ana RODRÍGUEZ TRABADO ; Carmen CÁMARA HIJÓN ; Alfonso RAMOS CANTARIÑO ; Silvia ROMERO-CHALA ; José Antonio GARCÍA-TRUJILLO ; Luis Miguel FERNÁNDEZ PEREIRA

Allergy, Asthma & Immunology Research.2016;8(5):412-420. doi:10.4168/aair.2016.8.5.412

PURPOSE: The basophil activation test (BAT) has been used to monitor venom immunotherapy (VIT) due to its high specificity. A previous study has reported a good correlation between a significant decrease in basophil activation during 5 years of VIT and clinical protection assessed by sting challenge. The following prospective study was performed to examine changes in basophil reactivity over a complete VIT period of 5 years. METHODS: BAT in a dose-response curve was studied prospectively in 10 hymenoptera venom-allergic patients over 5 years of VIT. BAT was performed at the time of diagnosis, 1 month after finishing the VIT build-up phase, and 3, 6, 12, 24, and 60 months after beginning treatment. The repeated measures ANOVA was applied to evaluate basophil activation changes throughout VIT. A cross-sectional study was also performed in 6 patients who received treatment for more than 3 years, and in another 12 patients who followed immunotherapy for at least 5 years. RESULTS: An early activation decrease was observed during the first 3 months of treatment, compared to pre-treatment values. This activation decrease was not maintained 6 to 18 months after treatment, but was observed again after 2 years of treatment, and maintained until the completion of the 5-year immunotherapy period. In cross-sectional analysis, the 6 patients who received treatment for 3 years, and 9 of the 12 patients who received treatment for 5 years, had negative BAT results. Three patients in this last group had positive BAT results and 2 patients had systemic reactions after field stings. CONCLUSIONS: BAT appears to be an optimal non-invasive test for close monitoring of VIT.
Basophils* ; Bites and Stings ; Cross-Sectional Studies ; Diagnosis ; Humans ; Hymenoptera ; Immunotherapy* ; Prospective Studies ; Sensitivity and Specificity ; Venoms*

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Does Spore Count Matter in Fungal Allergy?: The Role of Allergenic Fungal Species.

Wan Rou LIN ; Yi Hsing CHEN ; Mey Fann LEE ; Ling Yi HSU ; Chih Jen TIEN ; Feng Ming SHIH ; Shih Ching HSIAO ; Pi Han WANG

Allergy, Asthma & Immunology Research.2016;8(5):404-411. doi:10.4168/aair.2016.8.5.404

PURPOSE: Fungi have been known to be important aeroallergens for hundreds of years. Most studies have focused on total fungal concentration; however, the concentration of specific allergenic fungi may be more important on an individual basis. METHODS: Ten fungal allergic patients and 2 non-fungal allergic patients were enrolled. The patients with a decrease in physician or patient global assessment by more than 50% of their personal best were considered to have an exacerbation of allergic symptoms and to be in the active stage. Those who maintained their physician and patient global assessment scores at their personal best for more than 3 months were considered to be in the inactive stage. The concentrations of dominant fungi in the patients' houses and outdoors were measured by direct and viable counts at active and inactive stages. RESULTS: The exacerbation of allergic symptoms was not correlated with total fungal spore concentration or the indoor/outdoor ratio (I/O). Specific fungi, such as Cladosporium oxysporum (C. oxyspurum), C. cladosporioides, and Aspergillus niger (A. niger), were found to be significantly higher concentrations in the active stage than in the inactive stage. Presumed allergenic spore concentration threshold levels were 100 CFU/m3 for C. oxysporum, and 10 CFU/m3 for A. niger, Penicillium brevicompactum and Penicillium oxalicum. CONCLUSIONS: The major factor causing exacerbation of allergic symptoms in established fungal allergic patients may be the spore concentration of specific allergenic fungi rather than the total fungal concentration. These results may be useful in making recommendations as regards environmental control for fungal allergic patients.
Aspergillus niger ; Cladosporium ; Colony Count, Microbial* ; Family Characteristics ; Fungi ; Humans ; Hypersensitivity* ; Niger ; Penicillium ; Spores* ; Spores, Fungal

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