The Journal of allergy and clinical immunology
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J. Allergy Clin. Immunol. · Jan 2015
Classification of common variable immunodeficiencies using flow cytometry and a memory B-cell functionality assay.
The population of patients with common variable immunodeficiency (CVID) comprises a heterogeneous group of patients with different causes of hypogammaglobulinemia predisposing to recurrent infections, higher incidence of autoimmunity, and malignancy. Although memory B cells (memBcs) are key players in humoral defense and their numbers are commonly reduced in these patients, their functionality is not part of any current classification. ⋯ These data suggest almost normal memBc/immunoglobulin-secreting plasmablast functionality in some patients if sufficient stimulatory signals are delivered, which might open up opportunities for new therapeutic approaches.
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J. Allergy Clin. Immunol. · Dec 2014
Randomized Controlled Trial Multicenter StudyDupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis.
Severe atopic dermatitis (AD) has a high unmet need for effective and safe therapeutics. In early-phase trials, dupilumab, a fully human mAb targeting IL-4 receptor α, markedly improved disease activity, but the effect of IL-4/IL-13 blockade on AD at the molecular level has not been characterized. ⋯ This is the first report showing rapid improvement of the AD molecular signature with targeted anti-IL-4 receptor α therapy. These data suggest that IL-4 and IL-13 drive a complex, TH2-centered inflammatory axis in patients with AD.
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J. Allergy Clin. Immunol. · Dec 2014
IL-33 promotes ST2-dependent lung fibrosis by the induction of alternatively activated macrophages and innate lymphoid cells in mice.
The initiation and regulation of pulmonary fibrosis are not well understood. IL-33, an important cytokine for respiratory diseases, is overexpressed in the lungs of patients with idiopathic pulmonary fibrosis. ⋯ IL-33 is a novel profibrogenic cytokine that signals through ST2 to promote the initiation and progression of pulmonary fibrosis by recruiting and directing inflammatory cell function and enhancing profibrogenic cytokine production in an ST2- and macrophage-dependent manner.
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J. Allergy Clin. Immunol. · Nov 2014
Multicenter Study Clinical TrialIncreased frequency of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma.
TH2 cells can further differentiate into dual-positive TH2/TH17 cells. The presence of dual-positive TH2/TH17 cells in the airways and their effect on asthma severity are unknown. ⋯ Asthma is associated with a higher frequency of dual-positive TH2/TH17 cells in BAL fluid. The TH2/TH17(predominant) subgroup of asthmatic patients manifested glucocorticoid resistance in vitro. They also had the greatest airway obstruction and hyperreactivity compared with the TH2(predominant) and TH2/TH17(low) subgroups.
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J. Allergy Clin. Immunol. · Nov 2014
Clinical Trial Observational StudyOccupational asthma phenotypes identified by increased fractional exhaled nitric oxide after exposure to causal agents.
The added value of fractional exhaled nitric oxide (Feno) remains controversial in the investigation of occupational asthma (OA). ⋯ An increase in Feno after exposure to agents causing OA seems to occur more consistently in subjects with OA caused by high molecular weight than in those with OA due to LMW.