Hypertension, vascular inflammation and renal inflammation are characteristic of systemic lupus erythematosus (SLE), a multisystem autoimmune disease that is complex and poorly understood. Oxidation products of arachidonic and other fatty acids, termed isolevuglandins (isoLG) lead to formation of post-translational protein modifications that are immunogenic. We demonstrate isoLG enrichment in dendritic cells (DCs), B cells, and plasma cells from juvenile female B6.SLE123 mice. In adult B6.SLE123 and NZBWF1 mice, isoLG adducts are enriched in plasma cells and splenic DCs compared to C57Bl/6 and NZW mice respectively. Treatment with the isoLG-scavenger 2-hydroxybenzylamine (2-HOBA) reduced blood pressure, improved renal function, and attenuated renal injury. Moreover, 2-HOBA reduced bone marrow plasma cells, total IgG levels, and anti-dsDNA antibody titers. We also demonstrate that mice with SLE generate specific IgG antibodies against isoLG adducted protein, confirming the immunogenicity of isoLG adducts. Finally, we found that isoLG adducted peptides are markedly enriched in monocytes from patients with SLE which was accompanied by an increase in superoxide production. These findings support a role of isoLG adducts in the genesis and maintenance of systemic autoimmunity and its associated hypertension in SLE. Scavenging of isoLGs promises to be a novel therapy for this disease.

中文翻译：

---

异黄体素可促进系统性红斑狼疮的自身免疫和高血压

高血压，血管炎症和肾脏炎症是系统性红斑狼疮（SLE）的特征，系统性红斑狼疮是一种复杂且知之甚少的多系统自身免疫性疾病。花生四烯酸和其他脂肪酸的氧化产物，称为异levuglandins（isoLG），导致形成具有免疫原性的翻译后蛋白质修饰。我们展示了来自幼年雌性B6.SLE123小鼠的树突状细胞（DC），B细胞和浆细胞中的isoLG富集。在成年B6.SLE123和NZBWF1小鼠中，与C57Bl / 6和NZW小鼠相比，isoLG加合物的浆细胞和脾DC富集。用isoLG-清除剂2-羟基苄胺（2-HOBA）治疗可降低血压，改善肾功能并减轻肾损伤。此外，2-HOBA可减少骨髓浆细胞，总IgG水平，和抗dsDNA抗体滴度。我们还证明，患有SLE的小鼠产生针对isoLG加合物的特异性IgG抗体，证实了isoLG加合物的免疫原性。最后，我们发现isoLG加成的肽显着富集了SLE患者的单核细胞，并伴有超氧化物生成的增加。这些发现支持isoLG加合物在SLE的系统性自身免疫及其相关高血压的发生和维持中的作用。清除isoLGs有望成为该疾病的一种新型疗法。我们发现，isoLG加成肽在SLE患者的单核细胞中显着富集，并伴有超氧化物生成的增加。这些发现支持isoLG加合物在SLE的系统性自身免疫及其相关高血压的发生和维持中的作用。清除isoLGs有望成为治疗这种疾病的新方法。我们发现，isoLG加成肽在SLE患者的单核细胞中显着富集，并伴有超氧化物生成的增加。这些发现支持isoLG加合物在SLE的系统性自身免疫及其相关高血压的发生和维持中的作用。清除isoLGs有望成为该疾病的一种新型疗法。