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. 2023 Feb:135:102995.
doi: 10.1016/j.jaut.2023.102995. Epub 2023 Jan 30.

Significance of anti-transcobalamin receptor antibodies in cutaneous arteritis revealed by proteome-wide autoantibody screening

Kazuki M Matsuda  1 , Hirohito Kotani  1 , Kei Yamaguchi  2 , Taishi Okumura  2 , Eriko Fukuda  3 , Masanori Kono  4 , Teruyoshi Hisamoto  1 , Ruriko Kawanabe  1 , Yuta Norimatsu  1 , Ai Kuzumi  1 , Maiko Fukayama  1 , Takemichi Fukasawa  1 , Satoshi Ebata  1 , Asako Yoshizaki-Ogawa  1 , Tomohisa Okamura  4 , Hirofumi Shoda  4 , Keishi Fujio  4 , Naoki Goshima  2 , Shinichi Sato  5 , Ayumi Yoshizaki  6
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Free article

Significance of anti-transcobalamin receptor antibodies in cutaneous arteritis revealed by proteome-wide autoantibody screening

Kazuki M Matsuda et al. J Autoimmun. 2023 Feb.
Free article

Abstract

Cutaneous arteritis (CA) is a single-organ vasculitis that exclusively affects the small to medium-sized arteries of the skin. Diagnosis depends on a histological investigation with skin biopsy, which could be burdensome for both patients and clinicians. Moreover, the pathogenesis of CA remains unstudied, and treatment has not yet been established. Herein, we applied our proteome-wide autoantibody screening method to explore autoantibodies in the serum of CA patients. As a result, anti-transcobalamin receptor (TCblR) antibodies (Abs) were specifically detected in 24% of CA patients. Patients with positive anti-TCblR Abs were spared from peripheral neuropathy compared to those with negative anti-TCblR Abs, showing characteristics as CA confined to the skin. In addition, we revealed that anti-TCblR Abs trigger the autocrine loop of interleukin-6 mediated by tripartite motif-containing protein 21 in human endothelial cells and induce periarterial inflammation in murine skin. Furthermore, we demonstrated that methylcobalamin, a ligand of TCblR, ameliorates inflammation caused by anti-TCblR Abs both in vitro and in vivo. Collectively, our investigation unveils the pathologic significance of anti-TCblR Abs in CA and their potential as a diagnostic marker and a pathophysiology-oriented therapeutic target.

Keywords: Autoantibody; Autoimmunity; Cutaneous arteritis; Protein array; Transcobalamin; Vasculitis; Vitamin B12.

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Conflict of interest statement

Declaration of competing interest K Yamaguchi, T Okumura, and N Goshima are employed by ProteoBridge Corporation. T Okamura belongs to the Social Cooperation Program, Department of Functional Genomics and Immunological Diseases, supported by Chugai Pharmaceutical Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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