Association of high proprotein convertase subtilisin/kexin type 9 antibody level with poor prognosis in patients with diabetes: A prospective cross-sectional study

Abstract

Abstract Background 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. Therefore, we aimed to examine the clinical significance of PCSK9 antibody (PCSK9-Ab) levels. Methods We measured blood PCSK9-Ab and PCSK9 protein levels in 109 healthy donors (HDs) and 274 patients with diabetes mellitus (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. Results Although PCSK 9-Ab levels were significantly higher in the DM group than in the HDs group, PCSK9 protein levels were not significantly different. PCSK9-Ab 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, PCSK9-Ab levels were significantly associated with prognosis in patients with DM. Conclusions PCSK9-Ab may be a novel prognostic marker in patients with diabetes, and further studies are warranted to verify its usefulness.