RESUMO
BACKGROUND: Subcutaneous allergen-specific immunotherapy frequently causes allergic side effects and requires 30 to 80 injections over 3 to 5 years. OBJECTIVE: We sought to improve immunotherapy by using intralymphatic allergen administration (intralymphatic immunotherapy [ILIT]) and by targeting allergen to the MHC class II pathway. METHODS: Recombinant major cat dander allergen Fel d 1 was fused to a translocation sequence (TAT) and to part of the human invariant chain, generating a modular antigen transporter (MAT) vaccine (MAT-Fel d 1). In a randomized double-blind trial ILIT with MAT-Fel d 1 in alum was compared with ILIT with placebo (saline in alum) in allergic patients (ClinicalTrials.govNCT00718679). RESULTS: ILIT with MAT-Fel d 1 elicited no adverse events. After 3 placebo injections within 2 months, nasal tolerance increased less than 3-fold, whereas 3 intralymphatic injections with MAT-Fel d 1 increased nasal tolerance 74-fold (P < .001 vs placebo). ILIT with MAT-Fel d 1 stimulated regulatory T-cell responses (P = .026 vs placebo) and increased cat dander-specific IgG(4) levels by 5.66-fold (P = .003). The IgG(4) response positively correlated with IL-10 production (P < .001). CONCLUSION: In a first-in-human clinical study ILIT with MAT-Fel d 1 was safe and induced allergen tolerance after 3 injections.
Assuntos
Alérgenos/administração & dosagem , Dessensibilização Imunológica , Glicoproteínas/administração & dosagem , Hipersensibilidade/tratamento farmacológico , Linfócitos T Reguladores/efeitos dos fármacos , Adulto , Alérgenos/efeitos adversos , Alérgenos/genética , Alérgenos/metabolismo , Animais , Formação de Anticorpos/efeitos dos fármacos , Antígenos de Diferenciação de Linfócitos B/genética , Antígenos de Diferenciação de Linfócitos B/metabolismo , Gatos , Células Cultivadas , Feminino , Glicoproteínas/efeitos adversos , Glicoproteínas/genética , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Hipersensibilidade/fisiopatologia , Imunoglobulina G/sangue , Injeções Intralinfáticas , Interleucina-10/metabolismo , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/genética , Engenharia de Proteínas , Proteínas Recombinantes de Fusão/genética , Testes Cutâneos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Adulto JovemRESUMO
BACKGROUND: Spirometry reference values are important for the interpretation of spirometry results. Reference values should be updated regularly, derived from a population as similar to the population for which they are to be used and span across all ages. Such spirometry reference equations are currently lacking for central European populations. OBJECTIVE: To develop spirometry reference equations for central European populations between 8 and 90 years of age. MATERIALS: We used data collected between January 1993 and December 2010 from a central European population. The data was modelled using "Generalized Additive Models for Location, Scale and Shape" (GAMLSS). RESULTS: The spirometry reference equations were derived from 118'891 individuals consisting of 60'624 (51%) females and 58'267 (49%) males. Altogether, there were 18'211 (15.3%) children under the age of 18 years. CONCLUSION: We developed spirometry reference equations for a central European population between 8 and 90 years of age that can be implemented in a wide range of clinical settings.