RESUMEN
BACKGROUND: Allergic asthma is IgE-mediated and the IgE-sensitisation is usually demonstrated by skin prick tests (SPT) and IgE antibody determinations in serum. The SPT and IgE-antibody values do not directly predict if the allergy clinically contributes to the asthma. There is therefore a need for new objective tests that may indicate the clinical importance of an IgE-sensitisation. OBJECTIVE: To evaluate basophil allergen threshold sensitivity (CD-sens) as a measure of allergen sensitivity in allergic asthma. METHODS: Twenty-six subjects with stable, intermittent allergic asthma were tested with SPT and spirometry, and methacholine and allergen inhalation challenges to determine methacholine PD(20) (provocative dose causing a 20% drop in forced expiratory volume in 1 s) and allergen PD(20) . The results were compared with CD-sens and serological parameters, i.e. IgE- and IgG4 antibodies to the relevant allergens. RESULTS: A significant correlation was found between CD-sens and allergen PD(20) (P = 0.01; r = 0.49; n = 26) as well as between CD-sens and the ratio of allergen PD(20) to methacholine PD(20) (P = 0.007; r = 0.52; n = 26). In patients with a moderate to low degree of bronchial hyperresponsiveness there was an excellent correlation (P = 0.0001; r = 0.88, n = 13) between CD-sens and allergen sensitivity. No relation to either allergen PD(20) or the ratio was found for basophil allergen reactivity measured as CD63 up-regulation at high concentrations of the respective allergen. CONCLUSIONS AND CLINICAL RELEVANCE: CD-sens was found to be an objective marker of airway allergen sensitivity in stable allergic asthmatics, that may be used to predict airway responsiveness when bronchial challenge tests cannot be performed.
Asunto(s)
Alérgenos/inmunología , Asma/inmunología , Basófilos/inmunología , Adulto , Femenino , Humanos , Pruebas Inmunológicas , Exposición por Inhalación , Masculino , Cloruro de Metacolina/administración & dosificación , Cloruro de Metacolina/efectos adversos , Persona de Mediana Edad , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: This study reports the clinical and immunological state of patients 3 years after a 6-year period of Xolair treatment for severe allergic asthma. METHODS: The patient's cat allergen sensitivity, measured as CD-sens, IgE and IgE- and IgG4 antibodies, was analysed and compared with asthma severity evaluated from FEV(1) and a questionnaire. RESULTS: Three years after treatment with Xolair was stopped, 12/18 patients reported improved or unchanged asthma compared with ongoing Xolair treatment. Most of the patients were in a stable clinical condition, 16/18 had not increased nightly asthma attacks and 14/18 little or no increase in medication. The CD-sens to cat was still significantly lower (P < 0.02) than untreated patients with allergic asthma and lower than expected from their serum IgE antibody levels. CONCLUSION: Most of the patients in this study had, still 3 years after closing of 6 years Xolair treatment, a surprisingly mild and stable asthma. Interestingly, the observed, considerable, downregulation of basophil allergen sensitivity, CD-sens, most likely representing mast cell allergen sensitivity, contributed to the clinical results.
Asunto(s)
Antiasmáticos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Asma/tratamiento farmacológico , Basófilos/efectos de los fármacos , Adulto , Anciano , Alérgenos/inmunología , Animales , Anticuerpos Antiidiotipos , Anticuerpos Monoclonales Humanizados , Asma/inmunología , Basófilos/inmunología , Gatos , Ensayos Clínicos como Asunto , Estudios de Seguimiento , Volumen Espiratorio Forzado/efectos de los fármacos , Volumen Espiratorio Forzado/inmunología , Humanos , Hipersensibilidad/tratamiento farmacológico , Hipersensibilidad/inmunología , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Persona de Mediana Edad , Omalizumab , Encuestas y CuestionariosRESUMEN
BACKGROUND: Two atopic patients suffering from severe allergy difficult to handle by conventional medication were given Xolair despite an IgE level <30 kU/l. METHODS: Increasing dosages were given and monitored by clinical evaluation and CD-sens to clinically relevant allergens. The patients' IgE antibody fractions were 11-14%. RESULTS: Xolair dosages extrapolated from a recommended dose for IgE of 30-75 kU/l were adapted to the patients' IgE body pool but had very little effect. The double dose resulted in some clinical improvement and a decrease in CD-sens. However, not until the dose was doubled again did the patients become symptom free, although 1 patient needed some additional drugs but no oral steroids. CD-sens turned negative to 5 of the 7 tested allergens. CONCLUSIONS: Xolair is most useful also in atopics with an IgE level <30 kU/l. The dose must be adjusted to the size of the IgE antibody fraction adding all non-cross-reacting, clinically relevant specificities.
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Antialérgicos , Anticuerpos Monoclonales , Hipersensibilidad Inmediata/tratamiento farmacológico , Inmunoglobulina E/sangre , Adulto , Animales , Antialérgicos/administración & dosificación , Antialérgicos/uso terapéutico , Anticuerpos Antiidiotipos , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Gatos , Perros , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Hipersensibilidad Inmediata/etiología , Hipersensibilidad Inmediata/inmunología , Inmunoglobulina E/inmunología , Masculino , Omalizumab , Resultado del TratamientoRESUMEN
BACKGROUND: Current diagnosis of allergy and asthma to cat is confirmed using cat dander extract (CDE). We have previously engineered a recombinant major cat allergen, rFel d 1, with properties identical to the natural molecule. OBJECTIVE: The aim of the study was to evaluate IgE and IgG4 antibodies to rFel d 1 among sera from cat-allergic children and adults suffering from asthma and/or rhinoconjunctivitis (RC) in populations from Sweden and Austria. METHODS: Cat-allergic children and adults from Sweden (n=27 and 31, respectively) and Austria (n=41 and 41) with RC and/or asthma were selected. Sera were tested for IgE and IgG4 antibodies to CDE and rFel d 1 by CAP, and IgE to rFel d 1 by ELISA. Healthy subjects and non-cat-allergic patients (n=75) were included as controls. RESULTS: There was a high correlation between IgE responses to rFel d 1 and CDE among the 140 patients (r(s)=0.85, P<0.001); however, measured levels to rFel d 1 were on average 30% higher (P<0.0001). Ninety-eight percent of patients and none of the controls showed IgE to rFel d 1 and there was a threefold increased risk of asthma for half of the children with the highest IgE levels [odds ratio 3.23; 95% confidence interval (CI), 1.19-8.79] by ELISA. IgE responses to rFel d 1 among children with asthma were higher (median 19.4 kU/L) compared with children with RC (median 6.6 kU/L, P<0.05) and adults with asthma (median 3.0 kU/L, P<0.01). Furthermore, children with asthma displayed higher IgG4 levels than the asthmatic adults. CONCLUSION: A single recombinant molecule, rFel d 1, is at least as sensitive for in vitro diagnostics of cat allergy as the current extract-based test. Elevated IgE antibody levels to Fel d 1 are suggested to be a risk factor for asthma in cat-allergic children.
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Asma/diagnóstico , Conjuntivitis Alérgica/inmunología , Glicoproteínas/inmunología , Inmunoglobulina E/sangre , Rinitis Alérgica Perenne/inmunología , Adolescente , Adulto , Animales , Asma/inmunología , Gatos/inmunología , Niño , Preescolar , Conjuntivitis Alérgica/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina E/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Masculino , Prueba de Radioalergoadsorción , Proteínas Recombinantes/inmunología , Rinitis Alérgica Perenne/diagnóstico , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: To compare the efficacy of the Capcellia assay and the Dynabeads technique against the FACScount technique in the estimation of CD4 T-lymphocytes within a Nigerian setting. DESIGN: Prospective study. SETTING: Urban area in Nigeria. SUBJECTS: Ninety seven subjects (51 HIV seronegative and 46 HIV seropositive adults) seen in the blood banks and two out patient clinics in Lagos within the study period. MAIN OUTCOME MEASURES: Dynadeads technique with a higher correlation coefficient is a feasible alternative to the FACScount method. RESULTS: There was an overall correlation coefficient of r = 0.75 for CD4 cell counts as determined by the Dynabeads technique in comparison with the FACScount method. Also, an overall correlation coefficient of r = 0.17 for CD4 cell counts as determined by the Capcellia technique against the FACScount method. CONCLUSION: Dynabeads technique is simple to carry out and cheaper in terms of demand for human expertise and infrastructural requirements than the FACScounts. Therefore, it was recommended for use in the laboratory for monitoring of ARV therapy in Nigeria and any other resource poor
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Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/citología , Seropositividad para VIH/inmunología , Adolescente , Adulto , Recuento de Linfocito CD4/métodos , Linfocitos T CD4-Positivos/inmunología , Costos y Análisis de Costo , Femenino , Citometría de Flujo/métodos , Humanos , Separación Inmunomagnética/métodos , Masculino , Nigeria/epidemiología , Proyectos Piloto , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
The study diagnoses the relative impacts of the four known tropical Indo-Pacific drivers, namely, El Niño Southern Oscillation (ENSO), ENSO Modoki, Indian Ocean Dipole (IOD), and Indian Ocean Basin-wide mode (IOBM) on African seasonal rainfall variability. The canonical El Niño and El Niño Modoki are in general associated with anomalous reduction (enhancement) of rainfall in southern (northern) hemispheric regions during March-May season. However, both the El Niño flavours anomalously reduce the northern hemispheric rainfall during June-September. Interestingly, during boreal spring and summer, in many regions, the Indian Ocean drivers have influences opposite to those from tropical Pacific drivers. On the other hand, during the October-December season, the canonical El Niño and/or positive IOD are associated with an anomalous enhancement of rainfall in the Eastern Africa, while the El Niño Modoki events are associated with an opposite impact. In addition to the Walker circulation changes, the Indo-Pacific drivers influence the African rainfall through modulating jet streams. During boreal summer, the El Niño Modoki and canonical El Niño (positive IOD) tend to weaken (strengthen) the tropical easterly jet, and result in strengthening (weakening) and southward shift of African easterly jet. This anomalously reduces (enhances) rainfall in the tropical north, including Sahelian Africa.