No abstract

Ixabepilone had an acceptable safety profile at the MTD of 25 mg/m(2) (as a 30-min weekly infusion on a continuous 21-day schedule) and at 20 mg/m(2) (as a 1-h weekly infusion on a modified 28-day schedule). The clinical activity and acceptable tolerability profile warrant further single- or combination-agent evaluation.

An increase in immunoglobulin free light chains (FLC) was recently described in several pathological conditions, including asthma. FLC pathology is classically associated with monoclonal gammopathies. Its association with allergic disorders is surprising and unexplained. We therefore tested a cohort of children with severe atopic dermatitis (SCORAD 50–80) to determine the serum levels of free kappa and lambda chains, and correlated the results with clinical status and relevant laboratory markers. Seventy‐three patients with severe forms of AD, all children from 3 months to 3 years of age and ninety healthy age‐matched controls were included in the study. Light chains in sera were tested using the Freelite assay (Binding Site, Birmingham, UK). There were highly significant differences in both kappa (mean: 7.05 and 3.22 mg/l) and lambda (mean: 10.99 and 9.8 mg/l) serum levels between patients and controls, respectively (P < 0.0001). The kappa/lambda ratio in patients with allergy (mean: 0.64) was significantly higher than in controls (0.33) (P < 0.0001). We further observed significantly increased levels of FLC and their ratio in the group of patients with severe forms of AD in comparison to the group of patients with a resting stage of the disease or healthy controls (P < 0.05 and P < 0.0001, respectively). On the other hand, we could not confirm any association of FLC levels with age or total IgE levels. In conclusion, an increase in FLC reflects disease activity in children with severe atopic dermatitis. FLC might thus represent an additional diagnostic marker independent of total IgE levels.

Dendritic cells (DCs) are specific antigen‐presenting cells that play critical roles in the initiation and polarization of immune responses. DCs residing in the lungs might be detected in the bronchoalveolar lavage fluid (BALF). We analysed DC compartment in the peripheral blood and BALF of patients with allergy and in controls. Plasmacytoid and four distinct subsets of myeloid DCs [characterized by the expression of blood dendritic cell antigen (BDCA)‐1+ and ‐3+ and CD16 positivity or negativity] were detected in both tested compartments. We further evaluated the expression of C‐type lectins [mannose receptor (MR), dendritic cell‐specific intercellular adhesion molecule‐3‐grabbing non‐integrin (DC‐SIGN) and dendritic and epithelial cells (DEC)‐205] relevant to the pathogenesis of asthma. Interestingly, we found a selective increase in the frequency of myeloid DC‐expressing BDCA‐3 and MR particularly in BALF from allergic patients. Specific and highly statistically significant increase in BDCA‐3+ and/or MR+ DCs brings a novel characteristic to BAL analysis in allergic patients.