کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485735 | 1114365 | 2012 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Native-Like Aggregates of Factor VIII Are Immunogenic in von Willebrand Factor Deficient and Hemophilia a Mice
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کلمات کلیدی
Immunogenicity - ایمنی زاییImmunology - ایمونولوژیprotein aggregation - تجمع پروتئینcircular dichroism - رنگ تابی دورانیVon Willebrand factor - عامل فون ویلبراندFactor VIII - فاکتور 8Fluorescence spectroscopy - فوتولومینسانس یا فلوئورسانس یا فسفرسانسProteins - پروتئین هاHPLC - کروماتوگرافی مایعی کارا
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The administration of recombinant factor VIII (FVIII) is the first-line therapy for hemophilia A (HA), but 25%-35% of patients develop an inhibitory antibody response. In general, the presence of aggregates contributes to unwanted immunogenic responses against therapeutic proteins. FVIII has been shown to form both native-like and nonnative aggregates. Previously, we showed that nonnative aggregates of FVIII are less immunogenic than the native protein. Here, we investigated the effect of native-like aggregates of FVIII on immunogenicity in HA and von Willebrand factor knockout (vWFâ/â) mice. Mice immunized with native-like aggregates showed significantly higher inhibitory antibody titers than animals that received native FVIII. Following restimulation in vitro with native FVIII, the activation of CD4+ T-cells isolated from mice immunized with native-like aggregates is approximately fourfold higher than mice immunized with the native protein. Furthermore, this is associated with increases in the secretion of proinflammatory cytokines IL-6 and IL-17 in the native-like aggregate treatment group. The results indicate that the native-like aggregates of FVIII are more immunogenic than native FVIII for both the B-cell and the T-cell responses. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2055-2065, 2012
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 6, June 2012, Pages 2055-2065
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 6, June 2012, Pages 2055-2065
نویسندگان
Dipak S. Pisal, Matthew P. Kosloski, C. Russell Middaugh, Richard B. Bankert, Sathy V. Balu-iyer,