@article{oai:tsukuba.repo.nii.ac.jp:02001119, author = {Hiwasa, Takaki and Wang, Hao and Goto, Ken-ichiro and Mine, Seiichiro and Machida, Toshio and Kobayashi, Eiichi and Yoshida, Yoichi and Adachi, Akihiko and Matsutani, Tomoo and Sata, Mizuki and 山岸, 良匡 and YAMAGISHI, Kazumasa and Iso, Hiroyasu and Sawada, Norie and Tsugane, Shoichiro and Kunimatsu, Mitoshi and Kamitsukasa, Ikuo and Mori, Masahiro and Sugimoto, Kazuo and Uzawa, Akiyuki and Muto, Mayumi and Kuwabara, Satoshi and Kobayashi, Yoshio and Ohno, Mikiko and Nishi, Eiichiro and Hattori, Akiko and Yamamoto, Masashi and Maezawa, Yoshiro and Kobayashi, Kazuki and Ishibashi, Ryoichi and Takemoto, Minoru and Yokote, Koutaro and Takizawa, Hirotaka and Kishimoto, Takashi and Matsushita, Kazuyuki and Kobayashi, Sohei and Nomura, Fumio and Arasawa, Takahiro and Kagaya, Akiko and Maruyama, Tetsuro and Matsubara, Hisahiro and Tomiita, Minako and Hamanaka, Shinsaku and Imai, Yushi and Nakagawa, Tomoo and Kato, Naoya and Terada, Jiro and Matsumura, Takuma and Katsumata, Yusuke and Naito, Akira and Tanabe, Nobuhiro and Sakao, Seiichiro and Tatsumi, Koichiro and Ito, Masaaki and Shiratori, Fumiaki and Sumazaki, Makoto and Yajima, Satoshi and Shimada, Hideaki and Shirouzu, Mikako and Yokoyama, Shigeyuki and Kudo, Takashi and Doi, Hirofumi and Iwase, Katsuro and Ashino, Hiromi and Li, Shu-Yang and Kubota, Masaaki and Tomiyoshi, Go and Shinmen, Natsuko and Nakamura, Rika and Kuroda, Hideyuki and Iwadate, Yasuo}, journal = {BMC medicine}, month = {Jun}, note = {Background Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. Methods Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. Results The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297–311 of DIDO1, 426–440 of FOXJ2, and 607–621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case–control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. Conclusions Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.}, title = {Serum anti-DIDO1, anti-CPSF2, and anti-FOXJ2 antibodies as predictive risk markers for acute ischemic stroke}, volume = {19}, year = {2021}, yomi = {ヤマギシ, カズマサ} }