Svenungsson Elisabet, Engelbertsen Daniel, Wigren Maria, Gustafsson Johanna T, Gunnarsson Iva, Elvin Kerstin, Jensen-Urstad Kerstin, Fredrikson Gunilla Nordin, Nilsson Jan
Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Department of Clinical Sciences Malmö, Lund University, Sweden.
Clin Exp Immunol. 2015 Sep;181(3):417-26. doi: 10.1111/cei.12651. Epub 2015 Jun 22.
Increased production of autoantibodies is a characteristic feature of systemic lupus erythematosus (SLE) and there is evidence that several of these autoantibodies may contribute to increased cardiovascular disease (CVD) in SLE. Autoantibodies against the apolipoprotein (apo) B-100 peptides p45 and p210 have been associated with a lower CVD risk in non-SLE cohorts. The aim of the present study was to investigate how SLE affects the occurrence of these potentially protective autoantibodies. The study cohort consisted of 434 SLE patients and 322 age- and sex-matched population controls. Antibodies against native and malondialdehyde (MDA)-modified p45 and p210 were measured by enzyme-linked immunosorbent assay (ELISA). SLE patients had significantly lower levels of p210 immunoglobulin (Ig)G and p45 IgM (both the native and malondialdehyde (MDA)-modified forms). SLE patients with manifest CVD (myocardial infarction, ischaemic cerebrovascular disease or peripheral vascular disease) had lower levels p210 IgG and p45 IgM than SLE patients without CVD. Decreased levels of these autoantibodies were also observed in SLE patients with permanent organ damage, as assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (SDI). The present findings show that patients with SLE, a condition generally characterized by abundance of autoantibodies of multiple specificities, have reduced levels of antibodies against the apo B-100 antigens p45 and p210 and that the levels of these antibodies are reduced further in SLE patients with CVD. These observations suggest the possibility that an impaired antibody-mediated removal of damaged LDL particles may contribute to the development of vascular complications and organ damage in SLE.
自身抗体产生增加是系统性红斑狼疮（SLE）的一个特征，并且有证据表明其中几种自身抗体可能导致SLE患者心血管疾病（CVD）风险增加。在非SLE队列中，针对载脂蛋白（apo）B - 100肽p45和p210的自身抗体与较低的CVD风险相关。本研究的目的是调查SLE如何影响这些潜在保护性自身抗体的出现。研究队列包括434例SLE患者和322例年龄及性别匹配的人群对照。通过酶联免疫吸附测定（ELISA）检测针对天然和丙二醛（MDA）修饰的p45和p210的抗体。SLE患者的p210免疫球蛋白（Ig）G和p45 IgM（天然和MDA修饰形式）水平显著较低。患有明显CVD（心肌梗死、缺血性脑血管疾病或外周血管疾病）的SLE患者的p210 IgG和p45 IgM水平低于无CVD的SLE患者。根据系统性红斑狼疮国际协作临床研究/美国风湿病学会（ACR）损伤指数（SDI）评估，在有永久性器官损伤的SLE患者中也观察到这些自身抗体水平降低。本研究结果表明，SLE患者通常以多种特异性自身抗体丰富为特征，但针对apo B - 100抗原p45和p210的抗体水平降低，并且在患有CVD的SLE患者中这些抗体水平进一步降低。这些观察结果提示，抗体介导的受损低密度脂蛋白颗粒清除功能受损可能导致SLE患者血管并发症和器官损伤的发生。
