Effect of Trastuzumab-HER2 Complex Formation on Stress-Induced Modifications in the CDRs of Trastuzumab.

Asparagine deamidation and aspartic acid isomerization in the complementarity determining regions (CDRs) of monoclonal antibodies may alter their affinity to the target antigen. Trastuzumab has two hot spots for deamidation and one position for isomerization in the CDRs. Little is known how complex formation with its target antigen HER2 affects these modifications. Modifications in the CDRs of trastuzumab were thus compared between the free antibody and the trastuzumab-HER2 complex when stressed under physiological conditions at 37°C. Complex formation and stability of the complex upon stressing were assessed by size-exclusion chromatography. Deamidation of light-chain Asn-30 (Lc-Asn-30) was extensive when trastuzumab was stressed free but reduced about 10-fold when the antibody was stressed in complex with HER2. Almost no deamidation of heavy-chain (Hc-Asn-55) was detected in the trastuzumab-HER2 complex, while deamidation was observed when the antibody was stressed alone. Hc-Asp-102 isomerization, a modification that critically affects biological activity, was observed to a moderate degree when the free antibody was stressed but was not detected at all in the trastuzumab-HER2 complex. This shows that complex formation has a major influence on critical modifications in the CDRs of trastuzumab.

Factors associated with the appropriate use of asthma medications among adult asthmatic patients attending asthma clinic in a teaching hospital.

INTRODUCTION: asthma tends to be more severe with worse symptoms in Africa due to late diagnosis and delayed initiation of treatment. To identify patient and treatment-related factors which influence the appropriate use of asthma medications. METHODS: the study was institution based cross-sectional design. Patients were invited to provide information regarding the use of their asthma medications and factors potentially associated with appropriate use of these medications. A stepwise multivariate logistic regression analysis was used to evaluate the most important factor at a 0.05 level of significance. RESULTS: respondents with better knowledge of their asthma medications were more likely to use them appropriately (OR 5.82 [CI 95% 2.25-15.04]) as were those with positive attitudes and beliefs towards asthma and asthma medications (OR 3.88 [CI 95% 1.44-10.44]). CONCLUSION: patients need to understand the importance of adhering to the prescribed regimen for their asthma medications even in the absence of overt symptoms in order to optimize clinical outcome.