系统性红斑狼疮患者血清中 3-硝基酪氨酸水平的前瞻性测量:与疾病活动的相关性。

J C Oates, E F Christensen, C M Reilly, S E Self, G S Gilkeson
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摘要

系统性红斑狼疮(SLE)是一种典型的自身免疫性疾病。一氧化氮(NO)的过度产生与该病的发病机制有关。一些回顾性研究表明,血清硝酸盐和亚硝酸盐(NOx)与疾病活动之间存在相关性。外源性膳食和药物来源的一氧化氮会使这种一氧化氮生成量假性升高,血清中的硫醇也会使一氧化氮生成量降低。这些变量会使 NOx 成为研究 NO 在系统性红斑狼疮中作用的不太可靠的工具。亚硝酸过氧化物是一氧化氮和超氧化物的副产品,可硝化酪氨酸分子。由此产生的 3-硝基酪氨酸(3NT)可作为 NO 介导的蛋白质修饰的长期指标,不受外源性 NOx 或血清硫醇的影响。我们假设,由于这些原因,血清 3NT 水平与狼疮疾病活动的相关性将比血清 NOx 更显著。针对这一假设,我们对一组红斑狼疮患者的红斑狼疮疾病活动、血清蛋白 3NT 水平和氮氧化物水平进行了前瞻性评估,评估间隔时间为 3 个月。在非裔美国人中,血清 3NT 与疾病活动相关,而在白种人中,NOx 与疾病活动相关。活动性狼疮肾炎患者的血清 3NT 水平高于无肾病的患者。对活动性增生性狼疮肾炎患者肾活检组织的免疫组化分析显示,肾脏表达诱导性 NO 合酶。这项研究的结果表明,NO的过度生成可能在系统性红斑狼疮和狼疮性肾炎中起到致病作用。血清 3NT 可能是研究 NO 在系统性红斑狼疮发病机制中的作用的一种有用的新工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Prospective measure of serum 3-nitrotyrosine levels in systemic lupus erythematosus: correlation with disease activity.

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease. Overproduction of nitric oxide (NO) has been implicated in its pathogenesis. Several retrospective studies have indicated a correlation between serum nitrate and nitrite (NOx) and disease activity. This measure of NO production can be falsely elevated by exogenous dietary and medication sources of NOx and variably reduced by serum thiols. These variables can make NOx a less reliable tool for studying the role of NO in SLE. Peroxynitrite, a by-product of NO and superoxide, nitrates tyrosine moieties. The resulting 3-nitrotyrosine (3NT) serves as a long-term indicator of NO-mediated protein modifications that is not affected by exogenous sources of NOx or serum thiols. We hypothesized that for these reasons serum 3NT levels would correlate with lupus disease activity more significantly than serum NOx. To address this hypothesis, we prospectively evaluated lupus disease activity, serum protein 3NT levels, and NOx levels in a cohort of lupus patients at 3-month intervals. Serum 3NT correlated with disease activity among African-Americans, while NOx correlated with disease activity among Caucasians. Subjects with active lupus nephritis had higher levels of serum 3NT than those without renal disease. Immunohistochemical analysis of renal biopsies from subjects with active proliferative lupus nephritis revealed renal expression of inducible NO synthase. The results of this study suggest that overproduction of NO may play a pathogenic role in SLE and lupus nephritis. Serum 3NT may be a useful, new tool for studying the contributions of NO to the pathogenesis of SLE.

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