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Efficacy of a recombinant single-chain fragment variable region, VasSF, as a new drug for vasculitis.


ABSTRACT: Background:Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a pauci-immune disease with the inflammation of the small blood vessels. The efficacies of antibody drugs for induction therapies of vasculitis vary among cases. Here, we developed a novel clone of a single chain Fv region (ScFv) with vasculitis-specific therapeutic potential. Materials and methods:The clone, termed VasSF, was selected from our Escherichia coli expression library of recombinant human ScFv based on the therapeutic efficacy in an SCG/Kj mouse model of MPO-ANCA-associated vasculitis (MAAV), such as improvement of the urinary score and decreased crescent formation in glomeruli, granulomatous in lung, MPO-ANCA biomarkers, the anti-moesin antibody, and some cytokine levels. Results:We identified vasculitis-associated apolipoprotein A-II (VAP2) as a target molecule of the clone and confirmed the independently-established VAP2 antibodies were also therapeutic in SCG/Kj mice. In MAAV, MPO-ANCA and cytokines stimulate neutrophils by facilitating heterodimer formation of VAP2 with apolipoprotein A-I in HDL. Conclusion:VasSF would constitute a novel antibody drug for vasculitis by suppressing the heterodimer formation of the apolipoproteins.

SUBMITTER: Kameoka Y 

PROVIDER: S-EPMC6368128 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Efficacy of a recombinant single-chain fragment variable region, VasSF, as a new drug for vasculitis.

Kameoka Yosuke Y   Kishi Fukuko F   Koura Minako M   Yamakawa Yoshio Y   Nagasawa Rora R   Ito Fuyu F   Matsuda Junichiro J   Suzuki Osamu O   Nakayama Toshinori T   Suzuki Kazuo K  

Drug design, development and therapy 20190205


<h4>Background</h4>Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a pauci-immune disease with the inflammation of the small blood vessels. The efficacies of antibody drugs for induction therapies of vasculitis vary among cases. Here, we developed a novel clone of a single chain Fv region (ScFv) with vasculitis-specific therapeutic potential.<h4>Materials and methods</h4>The clone, termed VasSF, was selected from our <i>Escherichia coli</i> expression library of recomb  ...[more]

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