RESUMEN
BACKGROUND: Chronic rhinosinusitis with nasal polyps is generally characterized by local Th2 inflammation and is categorized into two subtypes in Japan: eosinophilic chronic rhinosinusitis (similar to chronic rhinosinusitis with nasal polyps in western countries) and non-eosinophilic chronic rhinosinusitis (characterized by Th1-dominant inflammation). OBJECTIVE: To investigate local IgE production and class switch recombination to IgE in these two subtypes of chronic rhinosinusitis with nasal polyps. METHODS: The identity of IgE-positive cells was determined using double-immunofluorescent staining for IgE and cell-type-specific molecular markers. To investigate the local class switch recombination to IgE and IgE synthesis in the mucosa, we performed real-time polymerase chain reaction to examine the mRNA expression of Th2 cytokines and class-switch-related molecules, including IL-4, IL-5, IL-13, ε germline gene transcripts, IgE mature transcript, IgG mature transcript, RAG1, RAG2 and activation-induced cytidine deaminase in eosinophilic polyps, non-eosinophilic polyps and controls. RESULTS: The concentrations of total IgE and number of IgE-positive cells were significantly higher in the eosinophilic polyps compared with control and non-eosinophilic polyps. IgE-positive cells were predominantly mast cells in eosinophilic polyps and significantly correlated with the number of FcεR1-positive cells in the subepithelial layer. IL-5 and IL-13 mRNA and ε germline gene transcripts expression levels were significantly higher in eosinophilic polyps compared with control and non-eosinophilic polyps. In contrast, the number of plasma cells and the expression of IgG mature transcripts were increased in non-eosinophilic polyps compared with eosinophilic polyps. RAG2 mRNA was significantly increased in both eosinophilic and non-eosinophilic polyps compared with control mucosa. CONCLUSION AND CLINICAL RELEVANCE: The current study suggests local class switching to IgE, production of IgE and IgE localization to the surface of mast cells in eosinophilic chronic rhinosinusitis in the Japanese population. The difference in the IgE-related profiles between eosinophilic chronic rhinosinusitis and non-eosinophilic chronic rhinosinusitis suggests heterogeneity in the pathogenesis of chronic rhinosinusitis with nasal polyps.
Asunto(s)
Cambio de Clase de Inmunoglobulina/genética , Inmunoglobulina E/genética , Inmunoglobulina E/inmunología , Pólipos Nasales/etiología , Rinitis/complicaciones , Sinusitis/complicaciones , Adulto , Anciano , Subgrupos de Linfocitos B/inmunología , Subgrupos de Linfocitos B/metabolismo , Enfermedad Crónica , Citocinas/genética , Citocinas/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Eosinófilos/inmunología , Femenino , Regulación de la Expresión Génica , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Cambio de Clase de Inmunoglobulina/inmunología , Inmunoglobulina E/metabolismo , Inmunoglobulina G/genética , Inmunoglobulina G/inmunología , Inflamación/inmunología , Inflamación/metabolismo , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Mucosa Nasal/inmunología , Mucosa Nasal/metabolismo , Mucosa Nasal/patología , Pólipos Nasales/diagnóstico , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fenotipo , Receptores de IgE/genética , Receptores de IgE/metabolismo , Rinitis/diagnóstico , Sinusitis/diagnósticoRESUMEN
AIM: To describe the features of chronic sinusitis associated with the use of tumour necrosis factor (TNF) inhibitors. METHODOLOGY: A retrospective review of the medical records between 2003 and 2011 revealed that five patients had developed chronic sinusitis after the start of TNF inhibitor administration and required rhinological evaluation and treatment. RESULTS: The incidence of refractory sinusitis associated with TNF inhibitors was approximately 2%. Of the five patients identified, four patients were medicated with etanercept and one with infliximab. The maxillary sinus was most commonly involved and cultures of the sinus discharge revealed Pseudomonas aeruginosa in three cases. Two patients showed improvement of sinusitis with antibiotic medication, despite the continuous use of TNF inhibitor, while in two other patients, sinusitis was resistant to antibiotic medication. Another patient who had developed recurrence of sinusitis after complete remission of previous chronic sinusitis by endoscopic sinus surgery showed remission only after cessation of TNF inhibitor. CONCLUSION: Chronic sinusitis associated with TNF inhibitors is considered to be a new disease entity, and it will become more common due to the increasing use of TNF inhibitors.