Department of Medicine, Rheumatology Unit, Karolinska Institutet and Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden.
Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
Arthritis Res Ther. 2018 Feb 26;20(1):36. doi: 10.1186/s13075-018-1530-2.
Immunoglobulin M (IgM) autoreactivity to malondialdehyde (MDA) protein modifications is part of the natural antibody repertoire in health and may have beneficial functions. In contrast, IgG anti-MDA are increased in chronic inflammation and autoimmunity and may instead have pathogenic properties.
Herein, we investigated serum IgG anti-MDA levels by enzyme-linked immunosorbent assay (ELISA) in 398 systemic lupus erythematosus (SLE) patients in the Swedish Karolinska SLE cohort and compared these to findings in 225 US SLE patients from New York University and Johns Hopkins University.
In two independent cohorts, IgG anti-MDA levels correlated positively with disease activity by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; p < 0.0001, Spearman R = 0.3). Meta-analysis found an odds ratio of 2.7 (confidence interval (CI) 1.9-3.9; p < 0.0001) for high anti-MDA IgG levels with active disease (SLEDAI ≥ 6). Furthermore, IgG anti-MDA correlated directly with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), soluble tumor necrosis factor receptors (sTNFR-1, sTNFR-2), and vascular cell adhesion molecule 1 (VCAM-1) measurements, and inversely with complement factors (C1q, C2, C3, C4). Importantly, IgG anti-MDA levels were significantly elevated in SLE patients with active nephritis (p = 0.0005) and correlated with cystatin C estimated glomerular filtration rate and albuminuria.
Elevated IgG anti-MDA in SLE patients was associated with high disease activity, with active lupus nephritis, and with biomarkers of systemic inflammation. This natural antibody reactivity may have potential prognostic utility, and may also actively contribute to pathogenesis.
免疫球蛋白 M（IgM）对丙二醛（MDA）蛋白修饰的自身反应是健康人群天然抗体库的一部分，可能具有有益的功能。相比之下，慢性炎症和自身免疫中 IgG 抗-MDA 增加，可能具有致病性。
本研究通过酶联免疫吸附试验（ELISA）检测了 398 例系统性红斑狼疮（SLE）患者的血清 IgG 抗-MDA 水平，并与来自纽约大学和约翰霍普金斯大学的 225 例美国 SLE 患者的检测结果进行了比较。
在两个独立的队列中，IgG 抗-MDA 水平与系统性红斑狼疮疾病活动指数（SLEDAI；p<0.0001，Spearman R=0.3）呈正相关。荟萃分析发现，伴有疾病活动（SLEDAI≥6）的患者中 IgG 抗-MDA 水平升高的比值比为 2.7（95%置信区间（CI）1.9-3.9；p<0.0001）。此外，IgG 抗-MDA 与红细胞沉降率（ESR）、C 反应蛋白（CRP）、可溶性肿瘤坏死因子受体（sTNFR-1、sTNFR-2）和血管细胞黏附分子 1（VCAM-1）直接相关，与补体因子（C1q、C2、C3、C4）呈负相关。重要的是，IgG 抗-MDA 水平在伴有活动性肾炎的 SLE 患者中显著升高（p=0.0005），与胱抑素 C 估计肾小球滤过率和蛋白尿相关。
SLE 患者 IgG 抗-MDA 升高与疾病活动度高、狼疮肾炎活动以及全身性炎症的生物标志物相关。这种天然抗体反应可能具有潜在的预后效用，并且可能也会积极参与发病机制。
