除了致病性自身抗体外，人体还会产生一些多克隆自身抗体，其生理作用和致病性未知。此外，人体中也存在针对胆固醇代谢必需酶前体转化酶亚锐头肽酶/凯辛型9 (PCSK9) 蛋白的血清抗体。PCSK9 还与胰岛素分泌和糖尿病（DM）有关。因此，我们旨在研究 PCSK9 抗体（PCSK9-Abs）水平的临床意义。我们使用放大荧光邻近原位同型酶联免疫吸附测定法，测量了109名健康供体（HDs）和274名 DM 患者（2型 DM 占89.8％）的血液 PCSK9-Abs 和 PCSK9 蛋白水平。随后，对 DM 患者进行了随访（平均：4.93年，标准差：2.77年，最大值：9.58年，最小值：0.07年），以研究抗体滴度与死亡率、心肌梗死、中风发作和癌症之间的关联。本研究的主要终点是研究 PCSK9-Abs 是否可以作为糖尿病患者总体死亡率的预测标志物。次要终点是研究 PCSK9-Abs 与临床参数之间的关系。尽管 DM 组和 HD 组的 PCSK9-Abs 和 PCSK9 蛋白水平都显著高于前者（p <0.008），但 PCSK9-Abs 和 PCSK9 蛋白水平两组都没有相关性。死亡率与较高的 PCSK9-Ab 水平显著相关，但与 PCSK9 蛋白水平无关。在调查潜在混淆因素后，较高的 PCSK9-Ab 水平仍然与 DM 患者的死亡率增加有关。 PCSK9-Abs 可能是糖尿病患者总体死亡率的一种新型预测标志物，有待进一步研究验证其有效性。 © 2023.作者（S）。

In addition to pathogenic autoantibodies, polyclonal autoantibodies with unknown physiological roles and pathogenicity are produced in the body. Moreover, serum antibodies against the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, which is integral to cholesterol metabolism, have also been observed. PCSK9 was also reported to be associated with insulin secretion and diabetes mellitus (DM). Therefore, we aimed to examine the clinical significance of PCSK9 antibodies (PCSK9-Abs) levels. We measured blood PCSK9-Abs and PCSK9 protein levels in 109 healthy donors (HDs) and 274 patients with DM (type 2 DM: 89.8%) using an amplified luminescence proximity homogeneous assay-linked immunosorbent assay. Subsequently, patients with DM were followed up (mean: 4.93 years, standard deviation: 2.77 years, maximum: 9.58 years, minimum: 0.07 years) to examine associations between antibody titers and mortality, myocardial infarction, stroke onset, and cancer. The primary endpoint of this study was to examine whether PCSK9-Abs can be a prognostic marker for overall mortality among the patients with diabetes. The secondary endpoint was to examine the relationship between PCSK9-Abs and clinical parameters. Although both PCSK9-Abs and PCSK9 protein levels were significantly higher in the DM group than in the HD group (p < 0.008), PCSK9-Abs and PCSK9 protein levels showed no correlation in either group. Mortality was significantly associated with higher PCSK9-Ab levels, but unrelated to PCSK9 protein levels. After investigating for potential confounding factors, higher PCSK9-Ab levels were still associated with increased mortality among the patients with DM. PCSK9-Abs may be a novel prognostic marker for overall mortality in patients with diabetes, and further studies are warranted to verify its usefulness.© 2023. The Author(s).