Effect of omalizumab as add-on therapy on asthma-related quality of life in severe allergic asthma: a Brazilian study (QUALITX).

OBJECTIVE: To assess the impact of omalizumab as an add-on therapy to standard treatment with inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA) on asthma-related quality of life (QoL) in patients with severe allergic asthma. METHODS: This was a 20-week, randomized, open-label, study involving Brazilian patients (>12 years) with severe persistent allergic asthma inadequately controlled despite regular treatment with, at least, ICS (≥500 µg/day fluticasone or equivalent) + LABA. The primary objective was to assess the mean change from baseline in overall Asthma-related Quality of Life Questionnaire (AQLQ) score in omalizumab-treated patients compared with the control group. Secondary outcome measures included rescue medication use, incidence of asthma exacerbations, perception of treatment efficacy among patients, mean change from baseline in AQLQ score, and >1.5-point increase in overall AQLQ score. RESULTS: In the omalizumab group, overall AQLQ score was 3.2 (0.9) (mean [SD]) at baseline and 4.4 (1.3) at week 20 versus 3.0 (1.0) at baseline and 3.0 (1.1) at week 20 in the control group. Mean change from baseline on overall AQLQ score at week 20 in the omalizumab group was 1.2 (0.2) versus 0 (0.1) in the control group, showing a significant increase in scores from baseline in the omalizumab group (p < .001). There was also a statistically significant difference (p < .001) in the number of patients who showed a >1.5-point increase from baseline in overall AQLQ score after 20 weeks, thus indicating a better QoL in the omalizumab group. There was no significant difference with respect to the use of rescue medication, incidence of asthma exacerbation, and adverse events between treatment groups. The global evaluation of treatment effectiveness was significantly better for omalizumab (p < .001). CONCLUSION: Omalizumab was well tolerated and significantly improved the overall AQLQ score. Hence, it is a potential add-on therapy for severe persistent allergic asthma not controlled by standard prescribed treatment in Brazilian patients.

Immune responses in breast cancer patients immunized with an anti-idiotype antibody mimicking NeuGc-containing gangliosides.

A phase I clinical trial was conducted in patients with stage III/IV breast cancer who were treated with the anti-idiotype mAb 1E10 specific to an Ab1 mAb able to react specifically with N-glycolyl-containing gangliosides and with antigens expressed on human melanoma and breast carcinoma cells. Patients were treated with 1 or 2 mg of aluminum hydroxide-precipitated 1E10 mAb every other week for six injections. Two patients at each dose were reimmunized 7-9 months after completing the induction phase. In hyperimmune sera from eight of the nine patients who received at least four doses of anti-Id vaccine preparations, strong specific responses were observed both against 1E10 mAb and NeuGc-GM3 ganglioside (Ab3 Id+Ag+). Nonclassical Ab1' antibodies (Id-Ag+) were also elicited by 1E10 mAb vaccine treatment. There were no differences between the two levels of dose tested in relation to toxicity and immunogenicity. No evidence of serious or unexpected effects was observed.

Auto-imunidade como imunodeficiência / Autoimmunity as immunodeficiency

As doenças auto-imunes näo podem mais ser atribuídas à simples presença de clones linfocitários auto-reativos, porque esses clones podem ser encontrados em indivíduos sadios como componentes de redes idiotípicas normais. Por outro lado, sídromes similares ao lúpus eritematoso sistêmico (LES) podem ser induzidas em camundongos normais pela injeçäo de um idiotipo anti-DNA freqüentemente encontrado em pacientes de LES (16/6), que também é encontrado no soro normal. Em camundongos NZB/W, que desenvolvem espontaneamente uma síndrome lupóide, ocorrem taxas anormalmente elevadas da ativaçäo de um subtipo de linfócitos T (Th2), que podem ser responsáveis pela ativaçäo policlonal de linfócitos B, levando à produçäo de vários auto-anticorpos patogênicos. A encefalomielite alérgica experimental (EAE) pode ser induzida em camundongos pela injeçäo de clones de células T reativos com a proteína básica da mielina (MBP); pode também ser prevenida ou revertida, pela injeçäo de outros clones MBP-reativos. O processo fisiológico de ativaçäo de linfócitos T requer a apresentaçäo de peptídios ligados a produtos do MHC na membrana de linfócitos B ou de vários tipos de "células apresentadas". Há porém, exceçöes a essa regra. Interaçöes recíprocas diretas entre regiöes variáveis de receptores de linfócitos T e imunoglobulinas atuando como receptores em linfócitos B podem resultar na ativaçäo de ambas as células. Em doenças parasitárias crônicas, como a esquistossomose mansônica e a doença de Chagas, podem ocorrer idiotipos antiparasita capazes de ativar linfócitos T autólogos independentemente de processamento/apresentaçäo. Neste ensaio, sugerimos que o "pareamento independente" de linfócitos T e B, contornando a necessidade de processamento/apresentaçäo, pode ser importante na gênese de doenças auto-imunes e nas formas severas de parasitoses crônicas. A eficácia de injeçöes de imunoglobulinas normais poliespecíficas no tratamento de várias doenças auto-imunes também sugere que a restauraçäo da saúde resulta do restabelecimento de padröes normais de conectividade idiotípica