Wang Gangduo, Pierangeli Silvia S, Papalardo Elizabeth, Ansari G A S, Khan M Firoze
University of Texas Medical Branch, Galveston, TX 77555-0438, USA.
Arthritis Rheum. 2010 Jul;62(7):2064-72. doi: 10.1002/art.27442.
Free radical-mediated reactions have been implicated as contributors in a number of autoimmune diseases, including systemic lupus erythematosus (SLE). However, the potential for oxidative/nitrosative stress to elicit an autoimmune response or to contribute to disease pathogenesis, and thus be useful when determining a prognosis, remains largely unexplored in humans. This study was undertaken to investigate the status and contribution of oxidative/nitrosative stress in patients with SLE.
Sera from 72 SLE patients with varying levels of disease activity according to the SLE Disease Activity Index (SLEDAI) and 36 age- and sex-matched healthy controls were evaluated for serum levels of oxidative/nitrosative stress markers, including antibodies to malondialdehyde (anti-MDA) protein adducts and to 4-hydroxynonenal (anti-HNE) protein adducts, MDA/HNE protein adducts, superoxide dismutase (SOD), nitrotyrosine (NT), and inducible nitric oxide synthase (iNOS).
Serum analysis showed significantly higher levels of both anti-MDA/anti-HNE protein adduct antibodies and MDA/HNE protein adducts in SLE patients compared with healthy controls. Interestingly, not only was there an increased number of subjects positive for anti-MDA or anti-HNE antibodies, but also the levels of both of these antibodies were statistically significantly higher among SLE patients whose SLEDAI scores were > or = 6 as compared with SLE patients with lower SLEDAI scores (SLEDAI score <6). In addition, a significant correlation was observed between the levels of anti-MDA or anti-HNE antibodies and the SLEDAI score (r = 0.734 and r = 0.647, respectively), suggesting a possible causal relationship between these antibodies and SLE. Furthermore, sera from SLE patients had lower levels of SOD and higher levels of iNOS and NT compared with healthy control sera.
These findings support an association between oxidative/nitrosative stress and SLE. The stronger response observed in serum samples from patients with higher SLEDAI scores suggests that markers of oxidative/nitrosative stress may be useful in evaluating the progression of SLE and in elucidating the mechanisms of disease pathogenesis.
自由基介导的反应被认为与包括系统性红斑狼疮（SLE）在内的多种自身免疫性疾病有关。然而，氧化/亚硝化应激引发自身免疫反应或促进疾病发病机制，进而在判断预后时发挥作用的可能性，在人类中仍 largely 未被探索。本研究旨在调查 SLE 患者氧化/亚硝化应激的状态和作用。
根据 SLE 疾病活动指数（SLEDAI），对 72 例疾病活动程度不同的 SLE 患者以及 36 例年龄和性别匹配的健康对照者的血清进行评估，检测氧化/亚硝化应激标志物的血清水平，包括丙二醛（MDA）蛋白加合物抗体、4-羟基壬烯醛（HNE）蛋白加合物抗体、MDA/HNE 蛋白加合物、超氧化物歧化酶（SOD）、硝基酪氨酸（NT）和诱导型一氧化氮合酶（iNOS）。
血清分析显示，与健康对照相比，SLE 患者中抗 MDA/抗 HNE 蛋白加合物抗体和 MDA/HNE 蛋白加合物的水平均显著更高。有趣的是，不仅抗 MDA 或抗 HNE 抗体阳性的受试者数量增加，而且与 SLEDAI 评分较低（SLEDAI 评分<6）的 SLE 患者相比，SLEDAI 评分≥6 的 SLE 患者中这两种抗体的水平在统计学上也显著更高。此外，观察到抗 MDA 或抗 HNE 抗体水平与 SLEDAI 评分之间存在显著相关性（分别为 r = 0.734 和 r = 0.647），表明这些抗体与 SLE 之间可能存在因果关系。此外，与健康对照血清相比，SLE 患者血清中 SOD 水平较低，iNOS 和 NT 水平较高。
这些发现支持氧化/亚硝化应激与 SLE 之间的关联。在 SLEDAI 评分较高的患者血清样本中观察到的更强反应表明，氧化/亚硝化应激标志物可能有助于评估 SLE 的进展并阐明疾病发病机制。
