Chlamydia pneumoniae Induces Interferon Gamma Responses in Peripheral Blood Mononuclear Cells in Children with Allergic Asthma.

Respiratory infections caused by Chlamydia pneumoniae have been associated with exacerbations of asthma. Cell-mediated immunity (CMI) is critical for maintaining immunity. We compared interferon (IFN)-γ responses in C. pneumoniae-infected peripheral blood mononuclear cells (PBMC) in paediatric patients ± asthma. Presence of C. pneumoniae was tested from asthma patients (N = 17) and non-asthmatic controls (N = 16) (PCR). PBMC were infected for 1 h ± C. pneumoniae AR-39 (MOI = 0.1) and cultured for 48 h. IFN-γ levels were measured in supernatants (ELISA). C. pneumoniae-IgG antibodies in serum were determined (MIF). All subjects tested negative for C. pneumoniae (PCR). C. pneumoniae-induced IFN-γ production in vitro was more prevalent in asthma compared with non-asthma; levels of IFN-γ were higher in asthma compared with non-asthma (P = 0.003). There was no association between recent respiratory infection and positive IFN-γ responses. These data show that C. pneumoniae modulates IFN-γ responses in patients with asthma, even in absence of active infection.

Chlamydia pneumoniae induces interleukin-12 responses in peripheral blood mononuclear cells in asthma and the role of toll like receptor 2 versus 4: a pilot study.

BACKGROUND: Chlamydia pneumoniae causes respiratory infection in adults and children, and has been associated with asthma exacerbations and induction of Immunoglobulin (Ig) E responses. We previously reported that C. pneumoniae enhances T helper (Th) 2 responses of peripheral blood mononuclear cells (PBMC) from asthmatic patients. It is likely that toll like receptor (TLR)-2 and TLR-4 mediate cytokine responses and host defense against C. pneumoniae. Thus, we sought to determine whether engagement of TLR-2 or TLR-4 may induce IL-12 production in our C. pneumoniae model. METHODS: PBMC (1.5 × 106) from asthmatic patients (N = 10) and non-asthmatic controls (N = 5) were infected or mock-infected for 1 h ± C. pneumoniae TW183 at a multiplicity of infection (MOI) = 1 and MOI = 0.1, and cultured for 48 h ± anti- TLR-2 and TLR-4 antibodies (Abs) (1 mg/mL). Interleukin (IL)-12 (48 h p.i.) and total IgE levels (day 10) were measured in supernatants (ELISA). RESULTS: High IgE levels were detected in supernatants of C. pneumoniae- infected PBMC from asthmatics on day 10, compared with mock-infected PBMC (p < 0.03). In contrast, IgE was not detected (<0.3 ng/mL) in either C. pneumoniae infected or mock-infected PBMC from non-asthmatics. IL-12 production by C. pneumoniae-infected asthmatic and non-asthmatic PBMC were similar. When anti-TLR4, but not anti-TLR2, was included in culture, IL-12 production by C. pneumoniae- infected asthmatic PBMC decreased. CONCLUSIONS: C. pneumoniae infection induces IgE production and modulates IL-12 responses in patients with asthma, which may be caused, in part, by differences in TLR-2 and TLR-4 stimulation.

Increased seroprevalence of Enterovirus 71 IgE antibodies in asthmatic compared with non-asthmatic children.

BACKGROUND: Asthma is a common pediatric chronic inflammatory airway disease. Respiratory viral infections are frequent infectious triggers for exacerbations of asthma. OBJECTIVE: We sought to determine whether Enterovirus 71 (EV71), a ubiquitous virus that causes systemic inflammatory responses in children but is not a known respiratory pathogen, can also serve as an infectious trigger for asthma. METHODS: Specific EV71 IgE and IgM antibodies (Abs), total serum IgE, and IL-2 and IL-4 cytokine levels in serum of asthmatic and non-asthmatic children (N = 42, ages 5-19; N = 35, ages 1-20, respectively) were measured (ELISA). RESULTS: Asthmatic children had higher EV71 IgE Ab levels than non-asthmatic (P < 0.001). Non-asthmatic children had significantly higher EV71 IgM Ab levels than asthmatic (P < 0.001). Despite low serum IgE levels of non-asthmatic, compared with asthmatic (P < 0.001), the non-asthmatic children produced significantly more IL-2 and IL-4 than asthmatic (P < 0.001; P < 0.001). The ages of the asthmatics, but not the non-asthmatics had a significant effect on the levels of EV 71 IgE Abs (P = 0.02; P = 0.356). A test of difference between these two slopes was significant. However, the ages of the non-asthmatic, but not the asthmatic children had a significant effect on the levels of EV 71 IgM Abs; a test of difference between these two slopes was significant. CONCLUSIONS: Increased specific EV71 IgE Ab responses may indicate that EV71 infection may also be an infectious trigger in asthma. However, the role of specific EV71 IgM Abs, Th2 cytokines, and age in non-asthmatic children should be further studied.

A retrospective study of peanut and tree nut allergy: Sensitization and correlations with clinical manifestations.

Peanut (PN) and tree nut (TN) allergies are among the leading causes of fatal food-induced anaphylaxis and are increasing in prevalence, especially in children. Their cosensitization and concurrent clinical allergy have been understudied. This retrospective study investigated the correlation between PN and TN allergy, both in terms of in vitro sensitization (IVS) and clinical allergic manifestations. We conducted a retrospective medical record review at the Allergy Clinic at University Hospital of Brooklyn. Fourteen hundred six charts were reviewed, of which 76 (5.4%) had documented relevant clinical allergy: PN allergy but not TN allergy (n = 29) or TN allergy but not PN allergy (n = 11) or both (n = 30). Six patients with PN allergy but no TN exposure history were not included in the analysis. The majority of patients (67/76, 88.1%) had a concurrent history of asthma, rhinoconjunctivitis, or AD. Sensitivity of TN IVS predicting PN IVS was 38/39 (97%). Similarly, sensitivity of PN IVS predicting TN IVS was 38/42 (91%). Sensitivity of TN clinical allergy predicting PN allergy was 30/59 (51%). Sensitivity of PN clinical allergy predicting TN allergy was 30/41 (73%). The total number of organ systems involved in reported clinical reactions correlated with IVS to TN (p = 0.004) but not IVS to PN (p = 0.983). In summary, we found PN sensitization predicts TN sensitization in vitro, with lower predictability for clinical reactions.

Allergic disease is associated with epilepsy in childhood: a US population-based study.

BACKGROUND: Previous studies using animal models suggest an association between allergic disease and epilepsy. We sought to determine whether allergic disease is associated with epilepsy in children. METHODS: We used the 2007-2008 National Survey of Children's Health, a US population-based study of 91 642 children aged 0-17 years to determine the association between the prevalence of epilepsy and allergic disease, including asthma, atopic dermatitis (AD)/eczema, hay fever, and food allergies. Multivariate logistic regression models were constructed that controlled for confounding variables. RESULTS: The US lifetime prevalence of childhood epilepsy was 1.03% and was significantly associated with older age, male sex, lower household income, family structure and history of brain injury or concussion. Children with ≥1 allergic disease had more epilepsy in their lifetime than nonallergic children (logistic regression, adjusted odds ratio [95% confidence interval] = 1.79 [1.37-2.33]). Lifetime prevalence (2.30 [1.50-3.52]) and one-year prevalence of asthma (2.00 [1.41-2.84]), AD/eczema (1.73 [1.17-2.56]), hay fever (1.93 [1.41-2.65]) and food allergies (2.69 [1.38-4.01]) were associated with increased odds of ever being diagnosed with epilepsy. Similar results were found for current history of epilepsy. Severe AD/eczema (3.89 [1.34-11.32]) [corrected] and hay fever (2.46 [1.11-5.41]) were associated with even higher odds of epilepsy compared with mild/moderate disease. As the number of allergic diseases increased, so did the odds of lifetime history and current history of epilepsy. CONCLUSIONS: The US prevalence of epilepsy is associated with allergic diseases in children. Further studies are needed to determine whether allergic inflammation contributes toward epileptogenesis.

Green tea (Camelia sinensis) mediated suppression of IgE production by peripheral blood mononuclear cells of allergic asthmatic humans.

Recent studies in our laboratory demonstrated the suppression of immunoglobulin E (IgE) production by green tea extract (GTE) in U266 cells. However, the effects of GTE or one of its components (EGCG) on IgE production by human peripheral blood mononuclear cells (PBMC) are unknown. PBMC (1.5 × 106) obtained from serum IgE+, allergic asthmatic patients, were cultured ± GTE (1-100 ng/ml) or purified EGCG (0.5-50 ng/ml), and IgE levels were determined on day 10 by enzyme-linked immunosorbent assay (ELISA). High levels of IgE were detected in supernatants of the PBMC cultures on day 10. When GTE was included in vitro, IgE production by PBMC was suppressed on day 10, compared with control. Purified EGCG included in vitro also suppressed IgE production, but at lower levels, compared with control. This study demonstrates that GTE and its major catechin, EGCG, have immunoregulatory effects on human IgE responses.

Obesity is associated with increased asthma severity and exacerbations, and increased serum immunoglobulin E in inner-city adults.

BACKGROUND: Obesity is associated with increased asthma and atopy. OBJECTIVE: To determine whether or not obesity in inner-city adults is associated with increased asthma prevalence, severity and exacerbations and IgE responses. METHODS: This retrospective study involved 246 adults with asthma and other atopic disorders who were seen at an asthma clinic in New York City between 1997 and 2010. Height, weight, asthma diagnosis and symptoms, peak flow (PF), spirometry, serum IgE levels and white blood cell differentials were recorded. RESULTS: Asthmatic patients had higher body mass index than non-asthmatics (median, interquartile range: 30.5, 10.2 vs. 27.8, 8.8; Mann-Whitney U-test, P = 0.0006). Class I and II/III obesity were associated with increased asthma (I: OR: 2.35, 95% CI: 1.04-5.34, P = 0.04; II/III: OR: 3.25, 95% CI: 1.36-7.74, P = 0.008). Class I and II/III obesity were associated with worsened asthma severity (ordinal logistic regression; I: OR: 4.23, 95% CI: 1.61-11.06, P = 0.003; II/III: OR: 2.76, 95% CI: 1.08-7.09, P = 0.03). Class II/III obesity was associated with increased asthma exacerbations requiring oral corticosteroids (repeated measures logistic regression, OR: 1.13, 95% CI: 1.03-1.25; P = 0.01) and increased requirement of inhaled corticosteroid for long-term asthma management (OR: 1.45, 95% CI: 1.29-1.62; P < 0.0001). In asthmatics, class II/III obesity was associated with decreased PF (general linear model, least squares mean ± SEM: 333.8 ± 37.4 vs. 396.2 ± 32.1 L/min; P = 0.007), forced expiratory volume in 1 s (75.2 ± 4.6 vs. 88.4 ± 5.6%; P = 0.03) and forced vital capacity (83.2 ± 4.7 vs. 109.2 ± 6.0%; P = 0.0002) and increased serum IgE (480.2 ± 88.3 vs. 269.0 ± 66.6 IU/mL; P = 0.04) and neutrophils (66.6 ± 3.7 vs. 60.1 ± 3.8%; P = 0.02). Class I obesity was also associated with increased serum IgE (458.7 ± 68.9, P = 0.03). CONCLUSION AND CLINICAL RELEVANCE: Obesity in inner-city adults may be both a risk and exacerbating factor for atopic asthma.

Early undifferentiated connective tissue disease (CTD). VI. An inception cohort after 10 years: disease remissions and changes in diagnoses in well established and undifferentiated CTD.

OBJECTIVE: (1) To review the diagnoses after 10 years in patients who were identified within 12 months of the onset of well established and undifferentiated connective tissue diseases (CTD). (2) To examine the death rates and disease remissions in these patients. METHODS: This inception cohort of 410 patients had less than one year of signs and/or symptoms of CTD. Diagnoses of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and poly/dermatomyositis (PM/DM) were made in 197 patients using accepted diagnostic and classification criteria. Diagnoses of undifferentiated CTD were made in 213 patients. These latter patients were placed in 3 categories: isolated Raynaud's phenomenon (RP), unexplained polyarthritis (UPA), and undifferentiated CTD (UCTD), defined as meeting at least 3 of 11 specific manifestations of CTD. The diagnoses and remissions in all patients after 10 years were determined. RESULTS: Patients with well established CTD tended to remain with the original diagnosis. The 10 year survival was at least 87% in all diagnostic categories, with the exception of SSc, in which it was 56%. The progression of UPA to RA occurred infrequently. The presence of antinuclear antibodies suggested that UPA may develop additional symptoms and/or a specific diagnosis, and RP in these patients increased the likelihood of progressing to UCTD or a specific well established CTD. Ten percent of patients with RP progressed to SSc. In patients with UCTD, joint pain/tenderness and swelling counts were associated with progression to other diagnoses including RA, while either serositis, malar rash, or discoid lupus suggested the eventual diagnosis of SLE. CONCLUSION: The survival of patients with SSc was poor, with most dying early in the course of their disease. Remissions were seen in all groups of patients except SSc. The remissions were sometimes transient in SLE. Undifferentiated disease at initial examination within 12 months of onset usually remains undifferentiated.