Blocking antibodies induced by allergen-specific immunotherapy ameliorate allergic airway disease in a human/mouse chimeric model.

BACKGROUND: Allergen-specific immunotherapy (AIT) induces specific blocking antibodies (Ab), which are claimed to prevent IgE-mediated reactions to allergens. Additionally, AIT modulates cellular responses to allergens, for example, by desensitizing effector cells, inducing regulatory T and B lymphocytes and immune deviation. It is still enigmatic which of these mechanisms mediate(s) clinical tolerance. We sought to address the role of AIT-induced blocking Ab separately from cellular responses in a chimeric human/mouse model of respiratory allergy. METHODS: Nonobese diabetic severe combined immunodeficient γc-/- (NSG) mice received intraperitoneally allergen-reactive PBMC from birch pollen-allergic patients together with birch pollen extract and human IL-4. Engraftment was assessed by flow cytometry. Airway hyperresponsiveness (AHR) and bronchial inflammation were analyzed after intranasal challenges with allergen or PBS. Sera collected from patients before and during AIT with birch pollen were added to the allergen prior to intranasal challenge. The IgE-blocking activity of post-AIT sera was assessed in vitro. RESULTS: Human cells were detected in cell suspensions of murine lungs and spleens indicating successful humanization. Humanized mice displayed a more pronounced AHR and bronchial inflammation when challenged with allergen compared to negative controls. Post-AIT sera exerted IgE-blocking activity. In contrast to pre-AIT sera, the presence of heterologous and autologous post-AIT sera significantly reduced the allergic airway inflammation and matched their IgE-blocking activity determined in vitro. CONCLUSION: Our data demonstrate that post-AIT sera with IgE-blocking activity ameliorate allergic airway inflammation in a human/mouse chimeric model of respiratory allergy independently of AIT-induced cellular changes.

[Cervicofacial involvement of primary cutaneous neuroendocrine carcinomas or Merkel cell tumors: therapeutic considerations]. / Localisations cervico-faciales des carcinomes neuroendocrines cutanés primaires ou tumeurs à cellules de Merkel: considérations thérapeutiques.

Seven cases of primary skin neuroendocrine carcinoma or Merkel cell tumours with cervico-facial localization are reported. The poor prognosis of these tumours is essentially due to the potential for local recurrence and the frequency of locoregional and visceral metastasis. Surgical treatment is required but rarely sufficient to control the disease. Complementary radiotherapy, when performed early, can reduce the rate of locoregional recurrence. Lymph node resection is important to determine prognosis but has not been proven to improve outcome. In addition, parotid metastasis appears to result from blood stream dissemination and has a very poor prognosis. Exclusive radiotherapy may be discussed in such cases.