ABSTRACT
WAS is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a WAS variant from 26 countries and a median follow-up of 8.9 years (0.3-71.1), totaling 6118 patient-years, were included in this international retrospective study. Overall survival (OS) of the cohort (censored at HSCT or GT) was 82% (95% CI 78-87) at 15 years and 70% (61-80) at 30 years of age. The type of variant was predictive of outcome: patients with a missense variant in exons 1 or 2 or with the intronic hotspot variant c.559+5G>A (class I variants) had a 15-year OS of 93% (89-98) and a 30-year OS of 91% (86-97), compared to 71% (62-81) and 48% (34-68) in patients with any other variant (class II; p<0.0001). The cumulative incidence rates of disease-related complications such as severe bleeding (p=0.007), life-threatening infection (p<0.0001), and autoimmunity (p=0.004) occurred significantly later in patients with a class I variant. The cumulative incidence of malignancy (p=0.6) was not different between classes I and II. This study represents the largest cohort of WAS patients studied so far. It confirms the spectrum of disease severity and quantifies the risk for specific disease-related complications. The class of variant is a biomarker to predict the outcome for WAS patients.
ABSTRACT
BACKGROUND: Therapy for allergic rhinitis aims to control symptoms and improve the quality of life. The treatment of allergic rhinitis includes allergen avoidance, environmental controls, pharmacologic treatment, and specific immunotherapy. OBJECTIVES: The aim of this study is to evaluate the clinical changes and the levels of interferon-gamma (IFN-gamma) and interleukin-5 (IL-5) in nasal lavage fluid from children with allergic rhinitis after different types of pharmacologic treatment (mometasone, montelukast, or desloratadine). METHODS: Twenty-four children aged from six to 12 years with moderate persistent allergic rhinitis were randomized into three groups receiving monotherapy treatment over four weeks: nasal corticosteroid (mometasone), leukotriene modifier (montelukast), or antihistamine (desloratadine). The perception of symptom improvement during the medication use was evaluated at the end of the treatment. Samples of nasal lavage fluid were collected before and after treatment for measuring IFN-gamma and IL-5 cytokines by ELISA. RESULTS: All parents perceived an improvement in symptoms. Significant enhancement was seen in the mometasone group compared to those with montelukast (P = 0.01) and desloratadine (P = 0.02). No significant differences were found among the three groups in the levels of IL-5 and IFN-gamma in nasal fluid at baseline or after treatment. Only the group treated with mometasone showed a slight but significant reduction in IL-5 levels after the treatment period as compared with levels before the treatment (P = 0.0469). CONCLUSION: The group treated with mometasone showed better improvement of clinical symptoms and a slight reduction in IL-5 levels in the nasal fluid. This may indirectly reflect the relative immunomodulatory effects of the drugs tested.
