Serum anti-DIDO1, anti-CPSF2, and anti-FOXJ2 antibodies as predictive risk markers for acute ischemic stroke.
Serum anti-DIDO1, anti-CPSF2, and anti-FOXJ2 antibodies as predictive risk markers for acute ischemic stroke.
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血清抗DIDO1、抗CPSF2和抗FOXJ2抗体作为急性缺血性卒中的预测风险标志物
DOI：
10.1186/s12916-021-02001-9
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发表时间：
2021-06-09
期刊：
影响因子：
9.3
通讯作者：
Iwadate Y
中科院分区：
文献类型：
--
作者：
Hiwasa T;Wang H;Goto KI;Mine S;Machida T;Kobayashi E;Yoshida Y;Adachi A;Matsutani T;Sata M;Yamagishi K;Iso H;Sawada N;Tsugane S;Kunimatsu M;Kamitsukasa I;Mori M;Sugimoto K;Uzawa A;Muto M;Kuwabara S;Kobayashi Y;Ohno M;Nishi E;Hattori A;Yamamoto M;Maezawa Y;Kobayashi K;Ishibashi R;Takemoto M;Yokote K;Takizawa H;Kishimoto T;Matsushita K;Kobayashi S;Nomura F;Arasawa T;Kagaya A;Maruyama T;Matsubara H;Tomiita M;Hamanaka S;Imai Y;Nakagawa T;Kato N;Terada J;Matsumura T;Katsumata Y;Naito A;Tanabe N;Sakao S;Tatsumi K;Ito M;Shiratori F;Sumazaki M;Yajima S;Shimada H;Shirouzu M;Yokoyama S;Kudo T;Doi H;Iwase K;Ashino H;Li SY;Kubota M;Tomiyoshi G;Shinmen N;Nakamura R;Kuroda H;Iwadate Y
急性缺血性中风(AIS)是一种严重的死亡和残疾原因。人工授精是导致死亡和残疾的严重原因。动脉粥样硬化的早期诊断是AIS的主要原因，可以在发病前进行治疗干预，从而预防AIS。采用基因表达文库血清学鉴定和蛋白质芯片技术筛选动脉粥样硬化患者血清抗体识别的抗原。以候选抗原来源的重组蛋白或合成肽为抗原，采用扩增发光均相联免疫吸附试验比较健康献血者和动脉粥样硬化相关疾病患者血清中的免疫球蛋白G水平。首次用蛋白质芯片技术筛选出死亡诱导因子1(DIDO1)、叉头盒J2(FOXJ2)、裂解和多聚腺苷化特异性因子(CPSF2)作为AIS患者血清抗体的靶抗原。然后，我们制备了谷胱甘肽S-转移酶融合的DIDO1蛋白以及DIDO1的297-311、FOXJ2的426-440和CPSF2的607-621氨基酸的多肽，用于检测血清抗体水平。与HD相比，AIS、短暂性脑缺血发作(TIA)和慢性肾脏病(CKD)患者的DIDO1蛋白和多肽抗体水平显著升高，而急性心肌梗死和糖尿病(DM)患者的DIDO1蛋白和多肽抗体水平无明显变化。血清抗FOXJ2抗体水平在大多数动脉粥样硬化相关疾病患者中升高，而血清抗CPSF2抗体水平与AIS、TIA和DM相关。受试者工作特征曲线显示血清DIDO1抗体水平与CKD高度相关，相关分析显示血清抗FOXJ2抗体水平与高血压相关。一项关于缺血性卒中的前瞻性病例对照研究证实，DIDO1蛋白、DIDO1、FOXJ2和CPSF2多肽的血清抗体水平在四分位数最高的患者中患AIS的风险比显著高于四分位数最低的患者，表明这些抗体标志物可作为AIS的危险因素。DIDO1、FOXJ2和CPSF2的血清抗体水平分别有助于预测由肾功能衰竭、高血压和糖尿病引起的动脉粥样硬化相关AIS的发病。网上版载有补充材料，可在10.1186/s12916-021-02001-9查阅。
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s12916-021-02001-9.
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影响因子：
3.8
作者：
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