Comprehensive autoantibody profiling in systemic autoimmunity by a highly-sensitive multiplex protein array
Ai Kuzumi, Yuta Norimatsu, Kazuki Matsuda, Chihiro Ono, Taishi Okumura, Emi Kogo, Naoki Goshima, Takemichi Fukasawa, Natsumi Fushida, Motoki Horii, Takashi Yamashita, Asako Yoshizaki‐Ogawa, Kei Yamaguchi, Takashi Matsushita, Shinichi Sato, Ayumi Yoshizaki
Abstract
Comprehensive autoantibody evaluation is essential for the management of autoimmune disorders. However, conventional methods suffer from poor sensitivity, low throughput, or limited availability. Here, using a proteome-wide human cDNA library, we developed a novel multiplex protein assay (autoantibody array assay; A-Cube) covering 65 antigens of 43 autoantibodies that are associated with systemic sclerosis (SSc) and polymyositis/dermatomyositis (PM/DM). The performance of A-Cube was validated against immunoprecipitation and established enzyme-linked immunosorbent assay. Further, through an evaluation of serum samples from 357 SSc and 172 PM/DM patients, A-Cube meticulously illustrated a diverse autoantibody landscape in these diseases. The wide coverage and high sensitivity of A-Cube also allowed the overlap and correlation analysis between multiple autoantibodies. Lastly, reviewing the cases with distinct autoantibody profiles by A-Cube underscored the importance of thorough autoantibody detection. Together, these data highlighted the utility of A-Cube as well as the clinical relevance of autoantibody profiles in SSc and PM/DM.