Allergic response to common environmental agents has been regarded as a main pathogenetic mechanism of bronchial asthma. However, allergic sensitization (atopy) can not be detected in a siginificant number of adult asthmatic patients. The etiology of nonatopic asthma has not yet been defined. To evaluate the possible involvement of autoimmune response against bronchial mucosa in the pathogenesis of nonatopic asthma, we performed indirect immunofluorescence staining of fresh frozen human bronchial mucosa tissue using serum samples from patients with atopic and nonatopic asthma, healthy controls, and patients with systemic lupus erythematosus. On immunostaining, circulating IgG autoantibodies against bronchial mucosa were detected in 2 (9.1%) of 22 patients with nonatopic asthma and in none of 22 patients with atopic asthma and of 22 healthy controls. IgG autoantibodies from the two patients with nonatopic asthma predominantly stained the cytoplasmic membrane of basal cells in bronchial epithelium. Serum samples from 10 patients with systemic lupus erythematosus immunostained the nucleus of epithelial cells in whole layer of bronchial epithelium. This study showed the presence of circulating IgG autoantibodies against the bronchial epithelial cell in a small portion of patients with nonatopic asthma. Further studies may be necessary to evaluate the possible involvement of autoimmune mechanism in the pathogenesis of nonatopic asthma.
Asthma/immunology* ; Autoantibodies/immunology* ; Autoantibodies/blood ; Bronchi/immunology* ; Epithelial Cells/immunology ; Human ; Immunity, Mucosal/immunology ; Respiratory Mucosa/immunology*

The pathogenetic mechanism of nonatopic asthma has not yet been defined. The idea of a possible involvement of autoimmunity in the pathogenesis of nonatopic asthma has been proposed by earlier studies. To evaluate the possible involvement of autoimmune response against bronchial epithelial cell in the pathogenesis of nonatopic asthma, we measured circulating autoantibodies to cultured human bronchial epithelial cell (BEAS-2B cell line) using enzyme-linked immunosorbent assay. We used stored serum samples form 38 age-matched healthy controls, 26 adult patients with atopic asthma, 16 adult patients with nonatopic asthma, and 12 adult patients with systemic lupus erythematosus. Levels of IgG autoantibodies to bronchial epithelial cell were significantly higher in patients with nonatopic asthma (mean+/-SD of absorbance values; 0.135+/-0.030) and systemic lupus erythematosus (0.293+/-0.181) than in healthy controls (0.112+/-0.016) and patients with atopic asthma (0.116+/-0.031) (p<0.05). This study showed that levels of circulating IgG autoantibodies to bronchial epithelial cell were increased in adult patients with nonatopic asthma. Further studies are needed to evaluate the possible involvement of autoimmune mechanism in the pathogenesis of nonatopic asthma.
Adult ; Asthma/*immunology ; Autoantibodies/*blood ; Bronchi/*immunology ; Cells, Cultured ; Epithelial Cells/immunology ; Human ; Hypersensitivity/immunology ; IgG/blood

OBJECTIVE: To compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis. METHODS: Demographic and clinical data were collected from 51 patients with asthma between January 2015 and December 2015. Routine blood and sputum induction tests were performed. Eosinophilic asthma was defined as induced sputum containing ⪖ 3% eosinophils, and neutrophilic asthma, as induced sputum containing ⪖ 71% neutrophils. Serum metabolic glycerophospholipid profile was determined by liquid chromatography-mass spectrometry. Differences in glycerophospholipid levels between eosinophilic and non-eosinophilic asthma and between neutrophilic and non-neutrophilic asthma were analyzed using partial least squares discriminant analysis. RESULTS: The serum lysophosphatidylglycerol level was significantly higher in the group with ⪖ 3% eosinophils in sputum than in the group with < 3% eosinophils in sputum. The area under the receiver-operating characteristic curve was ⪖ 70%. There was no significant difference in the serum metabolic glycerophospholipid profile between the group with sputum neutrophils ⪖ 71% and the group with sputum neutrophils < 71%. CONCLUSION Serum lysophosphatidylglycerol is produced abundantly in eosinophilic asthma and may be a biomarker of eosinophilic asthma. This information is helpful for identifying and tailoring treatment for the common asthma subtypes.
Adult ; Asthma ; blood ; immunology ; Eosinophils ; immunology ; Female ; Glycerophospholipids ; blood ; Humans ; Male ; Metabolomics ; Middle Aged ; Neutrophils ; immunology ; Sputum ; cytology ; immunology

Specific IgE to gliadin was proposed as a marker for wheat dependent exercise induced anaphylaxis, while Tri a 14 was found to induce IgE response in baker's asthma. We evaluated whether these components could be used for discriminating phenotypes of wheat allergy. Twenty-nine patients who were wheat-induced anaphylaxis and/or urticaria (n=21, group I) and baker's asthma (n=8, group II) were enrolled. The prevalence of serum specific IgE to Tri a 14 was higher in group II (25%) than in group I (4.8%), while the serum specific IgE to gliadin was significantly higher in group I (70%) than in group II (12.5%). The cutoff value for predicting the baker's asthma using the ratio of serum specific IgE to Tri a 14 to gliadin was 742.8 optical densityx1,000/(kU/L) with high sensitivity and specificity. These findings suggest that Tri a 14/gliadin may be a potential marker for predicting baker's asthma.
Adult ; Anaphylaxis/immunology ; Antigens, Plant/*immunology ; Asthma/blood/diagnosis/immunology ; Biological Markers/blood ; Carrier Proteins/*immunology ; Female ; Gliadin/*immunology ; Humans ; Immunoglobulin E/*blood/immunology ; Male ; Phenotype ; Triticum/immunology ; Urticaria/immunology ; Wheat Hypersensitivity/*diagnosis/*immunology

BACKGROUND & OBJECTIVES: The pathogenic mechanism of aspirin-sensitive asthma (ASA-BA) remains to be further defined. To evaluate the role of circulating immune complex (CIC) in ASA-BA. SUBJECTS & METHODS: We measured IgG- and IgA-IC level by ELISA using anti-C3 antibody in 33 ASA-BA patients whose sensitivity was confirmed by lysine-aspirin bronchoprovocation test, and compared with those of 14 allergic, 14 intrinsic asthma patients and 7 healthy controls. RESULTS: There was no significant difference in IgG-IC level among the four groups (p > 0.05), while IgA-IC levels of aspirin-sensitive asthma were higher than those of other groups (p = 0.0035). Patients with nasal polyp had significantly higher IgG-IC than those without it (p = 0.02). No differences were found according to medication and symptom scores, and presence of atopy, rhino-sinusitis, urticaria or concurrent sensitivity to sulfite (p > 0.05). Insignificant correlation was found between IgG-IC level and asthma duration, total IgE level, or circulating eosinophil count. CONCLUSION: These findings suggest a possible contribution of IgG-IC to the development of nasal polyp in ASA-BA. Further study will be needed to clarify the role of IgA-IC in the pathogenesis of ASA-BA.
Adult ; Aged ; Antigen-Antibody Complex/blood* ; Aspirin/adverse effects* ; Asthma/immunology* ; Asthma/etiology* ; Asthma/complications ; Case-Control Studies ; Human ; IgA/blood ; IgG/blood ; Middle Age ; Nasal Polyps/etiology

OBJECTIVETo investigate the distribution characteristics of serum specific IgE (sIgE) for inhaled allergens in children with different airway allergic diseases.

METHODSFluorescent enzyme-linked immunosorbent assay on the UniCAP250 system was performed to measure serum sIgE for 9 common inhaled allergens in 256 children aged 3-14 years with different airway allergic diseases. According to the clinical diagnosis, these children were divided into rhinitis group (37 children with allergic rhinitis), asthma group (82 children with bronchial asthma), and rhinitis-asthma group (137 children with allergic rhinitis complicated by bronchial asthma). The three groups were compared in terms of the detection rates of 9 inhaled allergens, sensitization level, and number of allergens.

RESULTSThe detection rate of serum sIgE for inhaled allergens was 57.3% (47/82) in the asthma group, 86.5% (32/37) in the rhinitis group, and 82.5% (113/137) in the rhinitis-asthma group (P<0.05). The most common allergen in the asthma, rhinitis, and the rhinitis-asthma groups was mould fungi (32.9%, 54.1%, and 48.9% respectively), followed by dust mites (30.5%, 45.9%, and 46.0% respectively), pollen (26.8%, 35.1%, and 32.8% respectively), pets (12.2%, 27.0%, and 18.2% respectively), and cockroach (9.8%, 5.4%, and 5.8% respectively). The rhinitis group and the rhinitis-asthma group had a significantly higher detection rate of mould fungi (mx2) than the asthma group (P<0.0166). There were no significant differences in the sensitization level of 9 allergens and number of allergens between the three groups.

CONCLUSIONSIn children with either bronchial asthma, allergic rhinitis, or bronchial asthma complicated by allergic rhinitis, the three most common inhaled allergens are mould fungi, dust mites, and pollens. Compared with bronchial asthma, allergic rhinitis may be more closely associated with sensitization by mould fungi. The three common airway allergic diseases have similar distribution characteristics of inhaled allergens.

Adolescent ; Allergens ; immunology ; Asthma ; immunology ; Child ; Child, Preschool ; Female ; Humans ; Immunoglobulin E ; blood ; Male ; Rhinitis, Allergic ; immunology

Higher levels of IgE-containing immune complexes (IC) have been reported in sera from patients with allergic diseases than in sera from controls. To evaluate the possibility of an IC-mediated mechanism in the pathogenesis of bronchial asthma, we measured circulating C3-containing IgE IC (C3-IgE IC) using anti-C3 ELISA from 20 house dust mite (HDM)-sensitive asthmatics, 20 non-atopic asthmatics, and 14 non-atopic controls. C3-IgE IC levels were significantly higher in HDM-sensitive asthmatics (mean +/- S.D.: 12.2 +/- 7.8 AU/ml) than in non-atopic asthmatics (6.5 +/- 7.5 AU/ml) or controls (5.8 +/- 4.4 AU/ml). C3-IgE IC levels were significantly correlated with HDM-specific IgE levels (r = 0.50, p<0.05), but not with total IgE levels (r = 0.36, p< 0.05) in HDM-sensitive atopic asthmatics. C3-IgE IC levels in sera did not significantly change during HDM-bronchoprovocation test in six HDM-sensitive asthmatics who showed positive reaction. Part of C3-IgE IC could be precipitated by protein G coupled beads. In conclusion, C3-IgE IC levels were elevated in sera from HDM-sensitive asthmatics; moreover IgG antibodies might be a component of C3-IgE IC. Our results suggest that an IgE IC-mediated mechanism could be involved in the pathogenesis of atopic asthma.
Adult ; Animal ; Antigen-Antibody Complex/*blood ; Asthma/*immunology ; Complement 3/*analysis ; Dust ; Human ; Immunoglobulin E/*blood ; Mites/immunology

OBJECTIVETo evaluate the effect of early intervention with Mycobacterium phlei F.U.36 injection on the balance of CD4⁺CD25⁺ regulatory T cells and Th17 cells in asthmatic mice, and to investigate the immunomodulatory effect of Mycobacterium phlei F.U.36.

METHODSThirty female BALB/c mice were randomly divided into three groups: normal control (n=10), asthma model (n=10) and Mycobacterium phlei F.U.36 treatment groups (n=10). A mouse model of asthma was prepared by injection and aerosol inhalation of chicken ovalbumin in the asthma model and Mycobacterium phlei F.U.36 treatment groups, while mice in the normal control group were given normal saline instead. The treatment group was intraperitoneally injected with Mycobacterium phlei F.U.36 (0.57 μg, once every other day) three times in the first two weeks after the first sensitization. All mice were sacrificed at 24 hours after the last challenge. Left lung tissues of these mice were obtained and made into sections for observation of inflammatory changes. The percentages of CD4⁺CD25⁺ regulatory T cells and Th17 cells in CD4⁺ T cells among splenic mononuclear cells were determined by flow cytometry. The levels of interleukin (IL)-10 and IL-17 in serum and bronchoalveolar lavage fluid were measured using ELISA.

RESULTSCompared with the normal control group, the asthma model group had significantly decreased percentages of CD4⁺CD25⁺ regulatory T cells and IL-10 levels (P<0.05) and significantly increased percentages of Th17 cells and IL-17 levels (P<0.05). Compared with the asthma model group, the Mycobacterium phlei F.U.36 treatment group had significantly increased percentages of CD4⁺CD25⁺ regulatory T cells and IL-10 levels (P<0.05) and significantly decreased percentage of Th17 cells and IL-17 levels (P<0.05).

CONCLUSIONSEarly intervention with Mycobacterium phlei F.U.36 can promote development of CD4⁺CD25⁺ regulatory T cells and production of IL-10 and inhibit generation of Th17 cells and production of IL-17 in asthmatic mice.

Animals ; Asthma ; immunology ; Cytokines ; biosynthesis ; Female ; Interleukin-10 ; blood ; Interleukin-17 ; blood ; Mice ; Mice, Inbred BALB C ; Mycobacterium phlei ; immunology ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology

Recently the prevalence of both asthma and obesity have increased substantially in many countries. The aim of this study was to evaluate the role of retinol-binding protein (RBP) 4 in childhood asthma and its association with atopy markers, pulmonary function, and bronchial hyperresponsiveness in relation to obesity. We studied 160 children between the ages 6 to 10 yr, including 122 asthmatics and 38 controls. The body mass index, pulmonary function tests, and methacholine challenge tests were measured on the same day. Total eosinophil count, serum total IgE, serum eosinophil cationic protein, and serum RBP4 were measured in all subjects. There was no difference in serum RBP4 levels between the asthmatics and the control group. In all subjects or subgroups, serum RBP4 was not associated with total eosinophil count, serum total IgE, serum eosinophil cationic protein, or PC20. There was no relationship between serum RBP4 and pulmonary function in female asthmatics. Forced expiratory volume in 1 second/forced vital capacity (FVC) and forced expiratory flow between 25% and 75% of FVC contributed to serum RBP4 in male asthmatics. Our findings show an association between RBP4 and pulmonary function in prepubertal male asthmatics. This relationship may indirectly affect the high prevalence of childhood asthma in males.
*Asthma/blood/immunology ; Bronchial Hyperreactivity/blood/immunology ; Bronchial Provocation Tests ; Child ; Female ; Humans ; Male ; Obesity/blood/immunology ; Retinol-Binding Proteins, Plasma/*metabolism

House dust mites have been known as the most important allergen in respiratory allergic diseases. Among several mite allergens, group I and group II antigens were recognized as major allergens. We measured specific IgE and IgG subclass antibodies against whole body antigen (WBA) and two major allergens of Dermatophagoides farinae (Der fI and Der fII) in sera from 66 adults with asthma (asthma group) and 34 normal subjects (healthy group) by ELISA. The mean O.D. values of WBA-specific IgE and IgG subclass antibodies in 100 studied sera were significantly higher than those of the two major allergens (p<0.001) and the level of Der fII- IgG1, IgG4 and IgE were higher than those of Der fI but IgG2 of Der fI was higher than that of Der fII (p< 0.001). The level of IgG4 of WBA were significantly higher in the atopic group than in the nonatopic group (1.280 +/- 0.634 v.s. 0.8290 +/- 0.388, p< 0.001), but the WBA- IgG1, IgG2, IgG3 were not different between the two groups. Among IgG subclass antibodies of Der fI, IgG2 was significantly higher in the nonatopic group than in the atopic group (1.7770 +/- 0.255 v.s. 1.636 +/- 0.390, p< 0.05) but there were no differences in IgG1, IgG3, and IgG4. Among IgG subclass antibodies of Der fII, IgG2 (1.534 +/- 0.380 v.s. 1.3010 +/- .431, p< 0.05) and IgG4 (1.09650 +/- .567 v.s. 0.708 +/- 0.146, p< 0.001) were significantly higher in the atopic group than in the nonatopic group. IgE antibodies to WBA, Der fI and Der fII were significantly higher in the atopic group (p< 0.001). There were significant correlationships between the levels of IgE and IgG4 of WBA (r = 0.60), Der fI (r = 0.33) and Der fII (r = 0.72). Even though there were no differences in the levels of allergen specific IgE and IgG subclass antibodies between nonatopic healthy and nonatopic asthmatic groups, the number of sera with prominent level of IgG2 of WBA were more common in the nonatopic asthmatic group (69% in nonatopic asthma group v.s. 28% in nonatopic healthy group, X2-test, p< 0.01).
Allergens/*blood ; Animal ; Antigens/*blood ; Asthma/*immunology ; Comparative Study ; Human ; Immunoglobulin E/*blood ; Immunoglobulin G/*blood ; Mites/*immunology ; Support, Non-U.S. Gov't