HAE1, also known as PRO98498, is structurally similar to omalizumab (Xolair (R)), a humanized anti-IgE IgG1 marketed for the treatment of asthma,

but differs by 9 amino acid changes in the complementarity-determining region resulting in a 23-fold improvement in affinity. HAE2 is similar to HAE1, but its Fc region was altered to reduce binding to Fc. receptors. As expected given the decreased binding to Fc gamma receptors, systemic exposure to pre-formed HAE2:IgE complexes in mice was greater (six-fold) and distribution to the liver lower (four-fold) compared with HAE1:IgE complexes. In monkeys, systemic exposure to HAE1 was similar to that previously observed for omalizumab in this species, but required comparatively lower serum drug concentrations to suppress free IgE levels. HAE2 treatment resulted in greater exposure and greater increase DMXAA mouse of total IgE, relative to HAE1, because of decreased clearance of HAE2:IgE complexes. Overall, these

data suggest that increased binding affinity to IgE may provide a more effective therapeutic for asthma patients, and that retaining Fc gamma R binding of Screening Library ic50 the anti-IgE antibody is important for elimination of anti-IgE: IgE complexes.”
“Background: Obesity and early menarche have been associated with asthma. In this report, we assess the association of Selleck MG-132 asthma with BMI and with changes in BMI from childhood to early adulthood. In addition, we determine if, in girls, any observed association of asthma with menarche can be explained by BMI. Methods: In a large national birth cohort, the associations of asthma at age 7, 11,

16 and 33 years with BMI, and of, asthma at age 33 years with changes in BMI from age 7 to age 33 years was assessed using logistic and mixed effects models as appropriate. Associations of asthma with age of menarche in girls were similarly assessed with and without adjustment for BMI. Results: Information on asthma, BMI, onset of menarche and confounders at all assessments was available for 1968 girls and 2223 boys. Obesity was relatively uncommon (<2%) in childhood. Overweight (BMI 25+) girls had more asthma. Girls with early menarche were more likely to be overweight. At age 11 years, asthma was associated with early menarche (OR=1.70, 95% CI 1.17-2.47, after adjustment for BMI OR=1.60, 95% CI 1.10-2.34). Across all ages, asthma was significantly associated with BMI (OR=1.50, 95% CI 1.18-1.90) but not with early menarche (OR=1.24, 95% CI 0.95-1.63). Conclusion: Asthma is more common in overweight girls. Early menarche is more common in overweight girls but this does not explain its association with asthma at age 11 years. Early menarche is not a risk factor for asthma at age 33 years in this cohort.