Aqueous intradermal low-dose house dust mite immunotherapy in tropical settings: a valid cost-effective approach for developing nations?

INTRODUCTION: Aqueous allergen injections, an effective and century-old technique, is considered a second-line approach in daily clinical practice. Inconveniences still surround conventional subcutaneous immunotherapy (SCIT) administration, such as a need for frequent injections, prolonged up-dosing schedules, elevated costs, and the unlikely possibility of a systemic reaction. The intradermal immunotherapy route (IDR) might favorably impact many of the aforementioned issues (Table 1). House dust mite (HDM) allergens are the main perennial sensitizers in the tropics, and as such, are solely employed in immunotherapy treatments. METHODS: We carried out a year-long real-life study in 25 perennial allergic rhinitis children, symptomatic on exposure to house dust, employing an intradermal low-dose allergen mix consisting of 50 ng of Dermatophagoides pteronyssinus/Dermatophagoides farinae and 120 ng of Blomia tropicalis, under a unique cost-wise protocol. Basal symptoms/signs and face Visual Analog Scale (fVAS) scores were recorded for 2 weeks and later compared with those registered throughout the 1-year treatment. Serum-specific IgG4 and IL-10 levels were employed in the assessment of the immune responses. RESULTS: Symptoms/signs and fVAS scores were significantly reduced from days 42 and 49, respectively, and remained so until treatment completion. Increases in specific IgG4's and IL-10 levels reflected significant immune responses. Injections were well tolerated and families reported improved health status (quality of life, QoL). CONCLUSIONS: A unique cost-effective immunotherapy alternative for deprived allergic communities in tropical settings is depicted; further research is needed.

Peripheral Th17/Treg cell-mediated immunity imbalance in allergic rhinitis patients.

INTRODUCTION: Allergic rhinitis (AR) is an IgE-mediated non-infectious disease of the nasal mucosa following contact with allergens. OBJECTIVE: To investigate the peripheral Th17 cells and CD4 + CD25 + Foxp3 + regulatory T (Treg) cells and the expression of cytokines in the serum of AR patients. METHODS: The peripheral blood of 14 patients with AR (AR group) and six healthy subjects (control group) was collected from March to May of 2012. Flow cytometry was performed to detect the Th17 cells and Treg cells, and enzyme-linked immunosorbent assay (ELISA) to measure the serum levels of IL-17 and TGF-ß1. RESULTS: The proportion of Th17 cells in the AR group was markedly higher than that in the control group (p < 0.01). The proportion of Treg cells in the AR group was also dramatically reduced when compared with the control group (p < 0.01). In the AR group, serum IL-17 levels were markedly higher than those in the control group (p < 0.01). In the AR group, serum TGF-ß1 levels were significantly lower than those in the control group (p < 0.01). CONCLUSION: The imbalance of peripheral Th17/Treg cells plays an important role in the pathogenesis of AR.

Desequilíbrio imunológico periférico mediado por células Th17/Treg em pacientes com rinite alérgica / Peripheral Th17/Treg cell-mediated immunity imbalance in allergic rhinitis patients

Introdução: A rinite alérgica (RA) é uma doença não infecciosa da mucosa nasal mediada por IgE após o contato com alérgenos. Objetivo: Investigar as células Th17 periféricas e CD4 + CD25 + Foxp3 + células T reguladoras (Treg) e a expressão sérica de citocinas em pacientes com RA. Métodos: De março a maio de 2012, foi coletado o sangue periférico de 14 pacientes com RA (grupo RA) e seis indivíduos saudáveis (grupo controle). A detecção das células Th17 e células Treg foi realizada através da citometria de fluxo e os níveis séricos de IL -17 e TGF- β1. Foram medidos por ELISA. Resultados: A percentagem de células Th17 no grupo RA foi bem maior do que no grupo controle (p < 0,01). A proporção de células Treg no grupo RA também foi drasticamente menor quando comparada ao grupo controle (p < 0,01). No grupo RA, o nível sérico de IL-17 foi significativamente maior do que no grupo controle (p < 0,01). Conclusão: O desequilíbrio de células Th17/Treg periféricas desempenha um papel importante na patogênese da RA. .

Introduction: Allergic rhinitis (AR) is an IgE-mediated non-infectious disease of the nasal mucosa following contact with allergens. Objective: To investigate the peripheral Th17 cells and CD4 + CD25 + Foxp3 + regulatory T (Treg) cells and the expression of cytokines in the serum of AR patients. Methods: The peripheral blood of 14 patients with AR (AR group) and six healthy subjects (control group) was collected from March to May of 2012. Flow cytometry was performed to detect the Th17 cells and Treg cells, and enzyme-linked immunosorbent assay (ELISA) to measure the serum levels of IL-17 and TGF-β1. Results: The proportion of Th17 cells in the AR group was markedly higher than that in the control group (p < 0.01). The proportion of Treg cells in the AR group was also dramatically reduced when compared with the control group (p < 0.01). In the AR group, serum IL-17 levels were markedly higher than those in the control group (p < 0.01). In the AR group, serum TGF-β1 levels were significantly lower than those in the control group (p < 0.01). Conclusion: The imbalance of peripheral Th17/Treg cells plays an important role in the pathogenesis of AR. .

[Levels of CD4+ and FOXP3+ lymphocytes in patients with allergic rhinitis]. / Concentraciones de linfocitos T CD4+ y FOXP3+ en pacientes con rinitis alérgica.

BACKGROUND: Allergic rinitis is the more common allergic disease, affecting to 25% of general population. Otitis media, sinusitis and other complications result from not controlled allergic rinitis. It has been reported that a low expression of FOXP3 marker on lymphocytes is associated with allergic diseases, and that allergen immunotherapy increases its synthesis. OBJECTIVE: To compare CD4+ FOXP3+ T cell levels in patients with allergic rhinitis, with and without allergen immunotherapy. METHODS: In this cross-sectional, observational and comparative study were included adult patients with allergic rinitis in two groups: one group with 29 patients under allergen immunotherapy for six months, and other group with 30 patients without immunotherapy. Lymphocyte markers CD3, CD4, CD8 y FOXP3 were determined in both groups, as well as serum immunoglobulins. RESULTS: In the group treated with immunotherapy the mean age was 36.4 years, and 72% of them were women. In the other group the age average was 40.4 years and 63% were women. There were no significant differences in immunoglobulin levels among both groups; IgG4 had higher levels, but not significant, in the immunotherapy group (82.1 vs 72.4 mg/dL, p=0.67). Patients from the group without immunotherapy had higher number of FOXP3+ lymphocytes, but not significant (8.2 vs 7.9, p=0.57). CONCLUSIONS: Patients treated with allergen immunotherapy had lower FOXP3+ lymphocytes number than those not treated. More studies are needed for considering FOXP3+ lymphocyte molecule as a useful marker in the follow-up of patients under immunotherapy.

Analysis of the flow-volume curve in children and adolescents with allergic rhinitis without asthma.

INTRODUCTION: There is epidemiological, functional and pathologic evidence that relates upper and lower airways, clinically known as a single respiratory tract. Patients with allergic rhinitis without asthma may present subclinical abnormal spirometry parameters. OBJECTIVES: To describe the results of the flow-volume curve in a group of patients with allergic rhinitis without asthma and analyze the possible associations between anthropometric, clinical and biochemical outcome measures with abnormal spirometry results. POPULATION AND METHODS: Observational, descriptive study including children and adolescents aged 6 to 18 years old with symptoms of allergic rhinitis without asthma. Age, gender, body mass index and duration of rhinitis were determined as per the subject's medical record. Allergen skin tests, flow-volume curve spirometry, determination of eosinophil count in blood and in nasal secretions, and total serum IgE were performed. RESULTS: A total of 84 patients were studied; 21 (25%; 95% CI: 15.1-34.8) presented at least one altered spirometry outcome measure. The FEV1/FVC ratio was the most affected outcome measure (10/84; 12%; 95% CI: 4.3-19.4). The multiple logistic regression analysis determined that spirometry alterations were associated with the number of blood eosinophils (OR: 1.00229; 95% CI: 1.00022-1.00436; p= 0.03) and the body mass index (OR: 1.31282; 95% CI: 1.08611-1.58685; p= 0.0049). CONCLUSIONS: Our results showed spirometry alterations in a considerable percentage of children and adolescents with allergic rhinitis without asthma. The blood eosinophil count and the body mass index could be associated with a sub-clinical alteration of pulmonary function.

Análisis de la curva flujo-volumen en niños y adolescentes con rinitis alérgica sin asma / Analysis of the fow-volume curve in children and adolescents with allergic rhinitis without asthma

Introducción. Existen evidencias epidemiológicas, funcionales y patológicas que vinculan las vías aéreas superior e inferior, reconocidas clínicamente como una vía aérea única. Los pacientes con rinitis alérgica sin asma podrían presentar anormalidades espirométricas subclínicas. Objetivos. Describir los resultados de las curvas fujo-volumen en un grupo de pacientes con rinitis alérgica sin asma y analizar las posibles asociaciones entre las variables antropométricas, clínicas y bioquímicas con los resultados anormales de las pruebas espirométricas. Población y métodos. Estudio observacional descriptivo, en el que se incluyeron niños y adolescentes de entre 6 y 18 años con síntomas de rinitis alérgica sin asma. Se estableció la edad, el sexo, el índice de masa corporal y la duración de la rinitis por la historia clínica. Se realizaron pruebas cutáneas con alérgenos, espirometría por curva fujo-volumen, determinación de eosinóflos en la sangre y la secreción nasal, e IgE sérica total. Resultados. Se estudiaron 84 pacientes; 21 (25%; IC 95% 15,1 a 34,8) presentaron alguna variable espirométrica alterada. El índice FEV1/FVC fue el más afectado (10/84; 12% IC 95% 4,3 a 19,4). El análisis de regresión logística múltiple determinó que la alteración espirométrica se asoció con el número de eosinóflos en la sangre (OR 1,00229; IC 95% 1,00022 a 1,00436; p= 0,03) y el índice de masa corporal (OR 1,31282; IC 95% 1,08611 a 1,58685; p= 0,0049). Conclusiones. Los resultados muestran la presencia de alteraciones espirométricas en un importante porcentaje de niños y adolescentes con rinitis alérgica sin asma. El recuento absoluto de eosinóflos en la sangre y el índice de masa corporal estarían asociados a la alteración subclínica de la función pulmonar.

Introduction. There is epidemiological, functional and pathologic evidence that relates upper and lower airways, clinically known as a single respiratory tract. Patients with allergic rhinitis without asthma may present subclinical abnormal spirometry parameters. Objectives. To describe the results of the fow-volume curve in a group of patients with allergic rhinitis without asthma and analyze the possible associations between anthropometric, clinical and biochemical outcome measures with abnormal spirometry results. Population and Methods. Observational, descriptive study including children and adolescents aged 6 to 18 years old with symptoms of allergic rhinitis without asthma. Age, gender, body mass index and duration of rhinitis were determined as per the subject's medical record. Allergen skin tests, fow-volume curve spirometry, determination of eosinophil count in blood and in nasal secretions, and total serum IgE were performed. Results. A total of 84 patients were studied; 21 (25%; 95% CI: 15.1-34.8) presented at least one altered spirometry outcome measure. The FEV1/FVC ratio was the most affected outcome measure (10/84; 12%; 95% CI: 4.3-19.4). The multiple logistic regression analysis determined that spirometry alterations were associated with the number of blood eosinophils (OR: 1.00229; 95% CI: 1.00022-1.00436; p= 0.03) and the body mass index (OR: 1.31282; 95% CI: 1.08611-1.58685; p= 0.0049). Conclusions. Our results showed spirometry alterations in a considerable percentage of children and adolescents with allergic rhinitis without asthma. The blood eosinophil count and the body mass index could be associated with a sub-clinical alteration of pulmonary function.

Análisis de la curva flujo-volumen en niños y adolescentes con rinitis alérgica sin asma / Analysis of the fow-volume curve in children and adolescents with allergic rhinitis without asthma

Introducción. Existen evidencias epidemiológicas, funcionales y patológicas que vinculan las vías aéreas superior e inferior, reconocidas clínicamente como una vía aérea única. Los pacientes con rinitis alérgica sin asma podrían presentar anormalidades espirométricas subclínicas. Objetivos. Describir los resultados de las curvas fujo-volumen en un grupo de pacientes con rinitis alérgica sin asma y analizar las posibles asociaciones entre las variables antropométricas, clínicas y bioquímicas con los resultados anormales de las pruebas espirométricas. Población y métodos. Estudio observacional descriptivo, en el que se incluyeron niños y adolescentes de entre 6 y 18 años con síntomas de rinitis alérgica sin asma. Se estableció la edad, el sexo, el índice de masa corporal y la duración de la rinitis por la historia clínica. Se realizaron pruebas cutáneas con alérgenos, espirometría por curva fujo-volumen, determinación de eosinóflos en la sangre y la secreción nasal, e IgE sérica total. Resultados. Se estudiaron 84 pacientes; 21 (25%; IC 95% 15,1 a 34,8) presentaron alguna variable espirométrica alterada. El índice FEV1/FVC fue el más afectado (10/84; 12% IC 95% 4,3 a 19,4). El análisis de regresión logística múltiple determinó que la alteración espirométrica se asoció con el número de eosinóflos en la sangre (OR 1,00229; IC 95% 1,00022 a 1,00436; p= 0,03) y el índice de masa corporal (OR 1,31282; IC 95% 1,08611 a 1,58685; p= 0,0049). Conclusiones. Los resultados muestran la presencia de alteraciones espirométricas en un importante porcentaje de niños y adolescentes con rinitis alérgica sin asma. El recuento absoluto de eosinóflos en la sangre y el índice de masa corporal estarían asociados a la alteración subclínica de la función pulmonar.(AU)

Introduction. There is epidemiological, functional and pathologic evidence that relates upper and lower airways, clinically known as a single respiratory tract. Patients with allergic rhinitis without asthma may present subclinical abnormal spirometry parameters. Objectives. To describe the results of the fow-volume curve in a group of patients with allergic rhinitis without asthma and analyze the possible associations between anthropometric, clinical and biochemical outcome measures with abnormal spirometry results. Population and Methods. Observational, descriptive study including children and adolescents aged 6 to 18 years old with symptoms of allergic rhinitis without asthma. Age, gender, body mass index and duration of rhinitis were determined as per the subjects medical record. Allergen skin tests, fow-volume curve spirometry, determination of eosinophil count in blood and in nasal secretions, and total serum IgE were performed. Results. A total of 84 patients were studied; 21 (25%; 95% CI: 15.1-34.8) presented at least one altered spirometry outcome measure. The FEV1/FVC ratio was the most affected outcome measure (10/84; 12%; 95% CI: 4.3-19.4). The multiple logistic regression analysis determined that spirometry alterations were associated with the number of blood eosinophils (OR: 1.00229; 95% CI: 1.00022-1.00436; p= 0.03) and the body mass index (OR: 1.31282; 95% CI: 1.08611-1.58685; p= 0.0049). Conclusions. Our results showed spirometry alterations in a considerable percentage of children and adolescents with allergic rhinitis without asthma. The blood eosinophil count and the body mass index could be associated with a sub-clinical alteration of pulmonary function.(AU)

Analysis of the flow-volume curve in children and adolescents with allergic rhinitis without asthma. / Analysis of the flow-volume curve in children and adolescents with allergic rhinitis without asthma.

INTRODUCTION: There is epidemiological, functional and pathologic evidence that relates upper and lower airways, clinically known as a single respiratory tract. Patients with allergic rhinitis without asthma may present subclinical abnormal spirometry parameters. OBJECTIVES: To describe the results of the flow-volume curve in a group of patients with allergic rhinitis without asthma and analyze the possible associations between anthropometric, clinical and biochemical outcome measures with abnormal spirometry results. POPULATION AND METHODS: Observational, descriptive study including children and adolescents aged 6 to 18 years old with symptoms of allergic rhinitis without asthma. Age, gender, body mass index and duration of rhinitis were determined as per the subjects medical record. Allergen skin tests, flow-volume curve spirometry, determination of eosinophil count in blood and in nasal secretions, and total serum IgE were performed. RESULTS: A total of 84 patients were studied; 21 (25

; 95

CI: 15.1-34.8) presented at least one altered spirometry outcome measure. The FEV1/FVC ratio was the most affected outcome measure (10/84; 12

; 95

CI: 4.3-19.4). The multiple logistic regression analysis determined that spirometry alterations were associated with the number of blood eosinophils (OR: 1.00229; 95

CI: 1.00022-1.00436; p= 0.03) and the body mass index (OR: 1.31282; 95

CI: 1.08611-1.58685; p= 0.0049). CONCLUSIONS: Our results showed spirometry alterations in a considerable percentage of children and adolescents with allergic rhinitis without asthma. The blood eosinophil count and the body mass index could be associated with a sub-clinical alteration of pulmonary function.

Humoral and cellular immune responses to Blomia tropicalis and concanavalin A-binding fractions in atopic patients.

Blomia tropicalis, Dermatophagoides pteronyssinus and D. farinae are prevalent house dust mites. Concanavalin A-binding components derived from B. tropicalis (Bt-ConA extract) are highly immunogenic in allergic diseases. The aim of the present study was to evaluate the humoral and cellular immune responses to B. tropicalis in mite-sensitized patients. A total of 137 patients with allergic rhinitis with/without asthma and 109 non-atopic subjects were selected and analyzed by the skin prick test, and for total serum IgE and specific IgE levels to both Bt-total and Bt-ConA extracts, their proliferative response and cytokine (IFN-gamma and IL-5) production by peripheral blood mononuclear cells (PBMC) stimulated with both extracts. Skin prick test showed that 70% of the patients were sensitized to Bt (Bt+) and similar levels of specific IgE to Bt-total and Bt-ConA extracts were demonstrable in Bt+ patients. Significant PBMC proliferation was observed in response to Bt-total extract in Bt+, but not in Bt- patients and non-atopic subjects (P < 0.001). Bt-ConA extract induced increased proliferative responses in all patient groups compared to medium alone (P < 0.05), but these responses were significantly decreased in the presence of the mannopyranoside ConA inhibitor (P < 0.05). Significant IFN-gamma production was observed after Bt-ConA stimulation of Bt+ patients (P < 0.05), while Bt-total extract had no effect. IL-5 production was consistently detected in Bt+ patients after allergen-specific stimulation or with no stimulus, indicating that PBMC from allergic patients are prone to produce Th2 profile cytokines, spontaneously or inductively by allergen restimulation. These data showed that ConA-binding components isolated from B. tropicalis may contain relevant antigens that are involved in both humoral and cellular immune responses. However, without an additional purification procedure to eliminate the residual contamination with ConA, its use in immunotherapeutic procedures cannot be recommended.

Humoral and cellular immune responses to Blomia tropicalis and concanavalin A-binding fractions in atopic patients

Blomia tropicalis, Dermatophagoides pteronyssinus and D. farinae are prevalent house dust mites. Concanavalin A-binding components derived from B. tropicalis (Bt-ConA extract) are highly immunogenic in allergic diseases. The aim of the present study was to evaluate the humoral and cellular immune responses to B. tropicalis in mite-sensitized patients. A total of 137 patients with allergic rhinitis with/without asthma and 109 non-atopic subjects were selected and analyzed by the skin prick test, and for total serum IgE and specific IgE levels to both Bt-total and Bt-ConA extracts, their proliferative response and cytokine (IFN-ã and IL-5) production by peripheral blood mononuclear cells (PBMC) stimulated with both extracts. Skin prick test showed that 70 percent of the patients were sensitized to Bt (Bt+) and similar levels of specific IgE to Bt-total and Bt-ConA extracts were demonstrable in Bt+ patients. Significant PBMC proliferation was observed in response to Bt-total extract in Bt+, but not in Bt- patients and non-atopic subjects (P < 0.001). Bt-ConA extract induced increased proliferative responses in all patient groups compared to medium alone (P < 0.05), but these responses were significantly decreased in the presence of the mannopyranoside ConA inhibitor (P < 0.05). Significant IFN-ã production was observed after Bt-ConA stimulation of Bt+ patients (P < 0.05), while Bt-total extract had no effect. IL-5 production was consistently detected in Bt+ patients after allergen-specific stimulation or with no stimulus, indicating that PBMC from allergic patients are prone to produce Th2 profile cytokines, spontaneously or inductively by allergen restimulation. These data showed that ConA-binding components isolated from B. tropicalis may contain relevant antigens that are involved in both humoral and cellular immune responses. However, without an additional purification procedure to eliminate the residual contamination with...

Mite-specific immunotherapy using allergen and/or bacterial extracts in atopic patients in Brazil.

OBJECTIVE: This study aimed to evaluate the clinical efficacy and antibody response changes after specific immunotherapy (SIT) using Dermatophagoides pteronyssinus (Dpt) allergens with or without bacterial extracts in Brazilian mite-atopic patients. METHODS: One-hundred patients with allergic rhinitis were selected for a randomized double-blind, placebo-controlled trial and distributed into 4 groups: Dpt (Dpt allergen extract), Dpt+MRB (Dpt allergen plus mixed respiratory bacterial extracts), MRB (MRB extract only) and placebo. Rhinitis symptom and medication scores; skin prick test (SPT) to Dpt extract; and serum immunoglobulin (Ig) E, IgG4, and IgG1 levels to Dpt, Der p 1, and Der p 2 allergens were evaluated before and after a year of treatment. RESULTS: After 1 year, the SPT response was reduced in the Dpt group (P=.03), whereas IgE levels to Der p 2 decreased only in the Dpt (P = .048) and Dpt+MRB (P = .005) groups. IgG4 and IgG1 levels to Dpt and Der p 1 increased in the Dpt group (P < .05), whereas in the Dpt + MRB group the IgG1 level only increased to Dpt (P=.001) and the IgG4 only increased to Der p 1 (P=.049). IgE levels to Dpt decreased only in the MRB (P= .005) and Dpt + MRB (P= .001) groups. Rhinitis symptom and medication scores fell in all groups, including the placebo group (P<.001). CONCLUSIONS: SIT using Dpt extract alone was effective in reducing SPT response and IgE levels to Der p 2 allergen, while bacterial extracts induced decreases in IgE levels to whole Dpt extract. However, only groups receiving Dpt allergen had higher levels of IgG1 and IgG4 to Dpt and Der p 1 after a year of treatment.

Safety and efficacy of fluticasone furoate in pediatric patients with perennial allergic rhinitis.

OBJECTIVE: To evaluate the safety and efficacy of once-daily (QD) fluticasone furoate (FF) nasal spray in children with perennial allergic rhinitis (PAR). STUDY DESIGN: A global, randomized, double-blind, placebo-controlled study. SUBJECTS AND METHODS: Pediatric patients (aged 2-11 years; n = 558) with PAR received once-daily placebo, FF 110 microg, or FF 55 microg for 12 weeks. Efficacy was evaluated by nasal symptom scores. General safety and corticosteroid-specific safety (nasal and ophthalmic examinations, and hypothalamic-pituitary-adrenal assessments) were assessed. RESULTS: No findings of clinical concern were identified from the safety assessments. For primary efficacy analysis of mean change from baseline over the first 4 weeks of treatment in daily reflective total nasal symptom score, FF 55 microg demonstrated significant improvement (P = 0.003) compared with placebo; however, the improvement for FF 110 microg versus placebo did not reach statistical significance (P = 0.073). CONCLUSION: FF QD was well tolerated and demonstrated efficacy in children aged 2 to 11 years with PAR.

Immunoblot analysis and comparative IgE responses of atopic patients to extracts of the domestic mite Blomia tropicalis.

BACKGROUND: The domestic mite Blomia tropicalis is found in subtropical and tropical environments, and its clinical importance as a sensitizing agent in allergic disease is widely accepted. OBJECTIVE: To investigate the IgE reactivity to allergens present in extracts of the domestic mite B. tropicalis, and compare the IgE responses to these allergens by asthmatics, patients with atopic dermatitis and allergic rhinitis, as well as nonatopic controls. METHODS: Extracts from B. tropicalis were used for skin tests. The B. tropicalis specific IgE in the serum were measured using the FAST Plus Test and immunoblot analysis. RESULTS: A total of 199 volunteers participated in the study. The data show that 18 out of 29 polypeptide bands present in extracts of this mite species were recognized by the allergic and control sera. Of these allergens, four showed a high IgE binding frequency and had relative molecular weights of 104, 80, 68 and 14 kDa. The 14 kDa allergen demonstrated the highest IgE binding frequency. CONCLUSION: Sera from atopic patients reacted to more allergens than sera from patients controls. Extracts from pure bodies of B. tropicalis contain one immunodominant and three important allergens. A common characteristic between all of the sera tested was the high degree of serum IgE reactivity observed to the 14 kDa allergen.

Immunoblot analysis and comparative IgE responses of atopic patients to extracts of the domestic mite Blomia tropicalis

BACKGROUND: The domestic mite Blomia tropicalis is found in subtropical and tropical environments, and its clinical importance as a sensitizing agent in allergic disease is widely accepted. OBJECTIVE: To investigate the IgE reactivity to allergens present in extracts of the domestic mite B. tropicalis, and compare the IgE responses to these allergens by asthmatics, patients with atopic dermatitis and allergic rhinitis, as well as nonatopic controls. METHODS: Extracts from B. tropicalis were used for skin tests. The B. tropicalis specific IgE in the serum were measured using the FAST Plus Test and immunoblot analysis. RESULTS: A total of 199 volunteers participated in the study. The data show that 18 out of 29 polypeptide bands present in extracts of this mite species were recognized by the allergic and control sera. Of these allergens, four showed a high IgE binding frequency and had relative molecular weights of 104, 80, 68 and 14 kDa. The 14 kDa allergen demonstrated the highest IgE binding frequency. CONCLUSION: Sera from atopic patients reacted to more allergens than sera from patients controls. Extracts from pure bodies of B. tropicalis contain one immunodominant and three important allergens. A common characteristic between all of the sera tested was the high degree of serum IgE reactivity observed to the 14 kDa allergen.

[Relation between IgE levels and infections in patients with allergic rhinitis and asthma]. / Relación entre concentraciones de IgE e infecciones en pacientes con rinitis y asma alérgica.

BACKGROUND: High IgE levels are frequent in allergic patients. The relationship between allergy and infections is controversial. Some diseases with cellular immunodeficiencies as well as with infections have high IgE levels, such as: hyper-IgE, Netherton, Wiskott-Aldrich, DiGeorge syndromes, AIDS, etc. In a previous retrospective study we found a high percentage of concurrent infections (two or more simultaneous infections) in atopic patients with IgE levels above 200 IU (OR 3.31; CI 95% 1.3 to 8.04; p < 0.01). The Th1/Th2 paradigm tries to explain the IgE elevation in atopy. A minor Th1 function would favor infectious processes by a reduction in TNF-alpha and IFNg. OBJECTIVE: To demonstrate if atopic patients with high IgE levels (> 200 IU) have more frequency of concurrent infections than patients with low levels. PATIENTS AND METHODS: In a cross sectional study we included patients with atopic rhinitis, asthma or both, in order to find upper and lower respiratory tract infections. RESULTS: We studied 143 patients (IgE mean, 389.07; SD 606.21). IgE levels were higher in children (521.25 UI) than in adults (204.03 UI) (p < 0.05). 73.44% of the patients had sinusitis; 5.59% pharyngotonsillitis; 17.93% otitis, and 7.74% laryngitis, without IgE mean differences. 42.84% had concurrent infections (IgE 296.16 IU) vs 57.15% without this processes (460.4 IU) (p = 0.11). When IgE levels were classified in high and low levels, with 200 IU as end point, we did not find differences in the number of infectious diseases. CONCLUSIONS: In this study high IgE levels did not have correlation with the higher frequency of concurrent infections.

Small bowel of patients with asthma and allergic rhinitis: absence of inflammation despite the presence of major cellular components of allergic inflammation.

Eosinophils participate in the pathogenesis of inflammatory diseases of the respiratory tract and the gut. We investigated the constitutive presence of eosinophils and mononuclear cells in the macroscopically normal duodenal mucosa of patients with asthma and allergic rhinitis. Macroscopically normal duodenal specimens were obtained at routine endoscopy for upper gastrointestinal symptoms from 16 patients with asthma and 13 patients with allergic rhinitis. Twelve nonatopic patients with irritable bowel syndrome were studied as controls. Specimens were analyzed by immunohistochemistry using a panel of antibodies to human eosinophil cationic protein clone EG1 (EG1) and clone EG2 (EG2), anti-human interleukin (anti-hIL)-5, anti-hIL-4, anti-CD4, and anti-CD68. Significantly increased numbers of eosinophils stained with EG1 and EG2 were found in the duodenum of patients with asthma and allergic rhinitis compared with controls. IL-5+ cells and IL-4+ cells were detected in significantly increased numbers in the duodenal mucosa of patients with asthma and rhinitis compared with controls. Mononuclear cells expressing CD4 (helper T cells) and CD68 (macrophages) also were significantly increased in the duodenal mucosa of asthma and rhinitis compared with controls. Accumulation of eosinophils in conjunction with IL-4+ cells and IL-5+ cells in the noninflamed duodenal mucosa may reflect a predominant T helper cell subset 2 systemic immune response in patients with asthma and allergic rhinitis. The absence of intestinal inflammation despite the marked presence of cells implicated in the allergic inflammation suggests that local mechanisms might determine the state of nonresponsiveness in the gut mucosa of patients with asthma and allergic rhinitis.

[Determination of interleukins and IgG4 in patients with allergic rhinitis with and without immunotherapy]. / Determinación de interleucinas e IgG4 en pacientes con rinitis alérgica, con y sin inmunoterapia.

BACKGROUND: Allergic rhinitis is the most common atopic reaction to allergens and may persist for many years if not treated. It is never lethal, though it may cause morbidity. The IgE synthesis is regulated by inheritance, antigen exposition and cytokines; specially Th2 cells, through secretions of the IL4 e IL5 that favor IgE production and inflammation rich in eosinophils. OBJECTIVE: To determine the difference of IgG4 serum levels, gamma interferon, and interleukins of patients with allergic rhinitis, with and without immunotherapy, and healthy patients. MATERIAL AND METHODS: In an observational, transversal, prospective, comparative and open study 82 (100%) patients were recruited and divided into three groups. Group 1 included 15 patients with allergic rhinitis diagnosis and positive skin tests without immunotherapy; group 2, 15 patients with allergic rhinitis diagnosis and positive skin tests with immunotherapy; group 3, 52 healthy patients. RESULTS: IL-4, IL-5, IL-6 and IL-12 values were higher in both groups of allergic rhinitis, compared with healthy group. There were differences in the IL-5 concentrations that were less in patients with allergic rhinitis and vaccine than in those without vaccine. The values of IgG4 and gamma interferon did not vary and were not found in the studied groups. CONCLUSION: The present study proved the existence of significant differences, showed increments in the interleukin values among healthy and allergic patients, despite allergic rhinitis is a local phenomenon. It is probable that the above is related to the genetic tendency to produce a Th2 cytokines pattern which is a characteristic of allergy. Allergen immunotherapy modified significantly the IL-5 levels as well as the other studied interleukins.

IGF-I, IGF-BP3, and GH serum levels after stimulation tests in prepubertal allergic boys.

The prevalence of short stature (SS, < 3rd percentile NCHS) among children with respiratory allergy (asthma and/or rhinitis) varies from 2% to 10%. In spite of several studies, the etiology of SS in those patients remains unknown. We evaluated growth hormone (GH) serum levels in response to two stimulating tests (standardized exercise and clonidine) in prepubertal boys (G1P1, Tanner; 8 years and 5 months to 14 years) with SS, 14 of them with respiratory allergy (A, positive skin prick test to D. pteronyssinus) and 5 nonallergic children (NA). Other causes of SS were excluded in both groups. Patients had mild asthma and/or rhinitis, and they had never received inhaled or systemic corticosteroid at any time. Tests were performed on different days, at least 1 week apart. [To prevent exercise-induced asthma, 30 min before the exercise test, allergic children inhaled disodium cromoglycate (2 mg)]. GH serum levels (Immunoassay, AIA-PACK HGH, Tosoh Co, Japan) were determined at the following times: exercise (E)--basal, 5, 15, and 30 min after exercising for 6 min; clonidine (C)--basal, 30, 60, and 90 min after clonidine (0.15 mg/m2 body surface) ingestion. A response was considered positive when GH serum levels reached the minimum of 10 ng/ml. Among (the allergic) A patients, four responded to both tests, five to C (clonidine) alone, four to E (exercise) alone and one had no response. Among NA, four had a positive response to both tests and one to C (clonidine) alone. The serum levels of insulin-like growth factor I (IGF-I) (DSL-5600 Active TM IGF-I Coated-Tube IRMA [DSL Lab Inc, USA]) and its binding protein (IGF-BP3) (DSL-6600 Active TM IGF-BP3 Coated-Tube IRMA [DSL Lab Inc, USA]) were within the normal range except for one A child. Bone age was delayed in relation to chronological age in all children, but adequate for height age. All children had delayed skeletal age in relation to chronological age, but bone age was normal for height. We concluded that in the children studied a deficiency of GH does not seem to be responsible for SS.

Determinacion serica de los niveles de ICAM-1s en pacientes con rinitis alergica / Serum levels of ICAM-1s in patient with allergic rhinitis

Se presume que la molécula de adhesión intercelular -1 (ICAM-1, CD54) está involucrada en la patogénesis del asma y se ha detectado una forma soluble de ICAM-1 (ICAM-1 s) en concentraciones elevadas en el suero de pacientes con ciertas condiciones inflamatorias. En este estudio, examinamos los niveles de ICAM-1 soluble en pacientes con rinitis alérgica de diversos grados: leve (8 pacientes), moderada (12 pacientes), severa (15 pacientes), del instituto de alergias, asma e inmunología. Los resultados fueron luego comparados con 10 sujetos saludables, como control negativo, sin diagnóstico de rinitis alérgica ni asma, y con 10 sujetos con asma de la unidad de neumología del Hospital La Samaritana, como control positivo. Todos los pacientes con edades entre 15 y 55 años. Utilizamos la técnica ELISA para medir ICAM-ls. Con anterioridad, todos los pacientes fueron sometidos a una prueba alérgica mediante el método Prick. Nuestro objetivo fue analizar si ICAM-1 s es un marcador de la severidad de la rinitis alérgica, y encontramos que los niveles de ICAM-1 soluble muestran un incremento a medida que la rinitis alérgica progresa. La comparación entre el grupo general de rinitis alérgica y el grupo de control negativo muestra resultados estadísticamente significativos (P < 0.05) y cada uno de los grupos de rinitis alérgica (leve, moderada y severa) en relación con el control negativo mostró que la expresión de ICAM-1 no incrementa y se mantiene baja, (Rinitis Leve p = 0.495, Moderada p = 0.0017, Severa p = 0.0014). Los anteriores resultados confirman nuestra hipótesis

Expression of nitric oxide synthases and in vitro migration of eosinophils from allergic rhinitis subjects.

The expression of nitric oxide (NO) synthases and the role of the NO cyclic GMP pathway on the migration of eosinophils from untreated patients with allergic rhinitis were investigated. Inducible NO synthase was strongly expressed in eosinophils from healthy individuals, but not in eosinophils from allergic rhinitis patients. The neuronal isoform was observed in eosinophils from each group studied, whereas no staining for the endothelial isoform was detected in either group. The chemotaxis to N-formyl-methionyl-leucyl-phenylalanine (fMLP, 5 x 10(-7) M) and eotaxin (100 ng/ml) was significantly potentiated in allergic rhinitis eosinophils. In both groups, N(omega)-nitro-L-arginine methyl ester (L-NAME, 1.0 mM) or 1H(1,2,4)-oxadiazolo(4,3,-a)quinoxalin-1-one (ODQ, 0.2 mM) markedly reduced the chemotaxis. The selective iNOS inhibitor N-(3-(aminomethyl)benzyl)acetamidine (1400 W, 0.1-1.0 mM) significantly reduced the chemotaxis of eosinophils from healthy but not from allergic rhinitis subjects. The inhibition by L-NAME was restored by 3-morpholinosydnonimine (SIN-1) and S-nitroso-N-acetyl-penicillamine, whereas the inhibition by ODQ was restored by dibutyryl cyclic GMP. In conclusion, both endothelial and inducible NO synthase isoforms are absent in allergic rhinitis eosinophils, suggesting that the NO cyclic GMP pathway in this cell type is maintained through the activity of a neuronal isoform.