Immunological origin and functional properties of catalytic autoantibodies to amyloid beta peptide.
Immunological origin and functional properties of catalytic autoantibodies to amyloid beta peptide.
复制标题
淀粉样β肽催化自身抗体的免疫学起源和功能特性。
DOI：
10.1007/s10875-010-9414-5
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发表时间：
2010
影响因子：
9.1
通讯作者：
Nishiyama,Yasuhiro
中科院分区：
文献类型：
--
作者：
Paul,Sudhir;Planque,Stephanie;Nishiyama,Yasuhiro
ObjectivesObjectives The objectives of this study are to (1) evaluate the ability of the immune system to synthesize specific antibodies that catalyze the degradation of amyloid β peptide (Aβ) and to (2) evaluate the prospect of developing a catalytic IVIG (CIVIG) formulation for therapy of Alzheimer’s disease (AD).ConclusionsPolyclonal autoantibodies from humans without dementia hydrolyzed Aβ specifically. The catalytic activity improved as a function of age. Patients with AD produced catalytic antibodies at increased levels. IgM-class antibodies expressed the activity at levels superior to IgGs. Production of catalytic autoantibodies appears to be an innate immunity function with adaptive improvements occurring upon Aβ overexpression, which suggests a beneficial function of the catalytic activity. The catalytic autoantibodies impeded Aβ aggregation, dissolved preformed Aβ aggregates, and inhibited Aβ cytotoxicity in tissue culture. Recombinant catalytic antibodies from a human library have been identified, validating the phenomenon of antibody-catalyzed Aβ cleavage. As a single catalyst molecule inactivates multiple Aβ molecules, catalytic antibodies may clear Aβ efficiently. IVIG did not cleave Aβ, indicating the importance of purification procedures that maintain catalytic site integrity. Traditional Aβ-binding antibodies form immune complexes that can induce inflammatory reaction and vascular dysfunction. Catalysts do not form stable immune complexes, minimizing these risks. Criteria appropriate for developing a CIVIG formulation with potential therapeutic utility are discussed, including isolation of the Aβ-specific catalytic subsets present in IgM and IgG from human blood.
