Elevated lipid peroxidation biomarkers in autoimmune diseases: A systematic review and meta-analysis

IF 8.3 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews Pub Date : 2026-03-01 Epub Date: 2026-02-16 DOI:10.1016/j.autrev.2026.104008

Yixiang Luo , Siqi Hua , Tongtong Song, Mingxin Cao, Shuangshuang Song, Shentong Fang, Bo Zhu

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Abstract

Background

Ferroptosis, an iron-dependent cell death pathway driven by lipid peroxidation (LPO), is implicated in the pathogenesis of autoimmune diseases (AIDs). However, comprehensive clinical evidence establishing the association between specific LPO biomarkers and AIDs is lacking.

Objective

To systematically evaluate the clinical evidence for elevated LPO in major AIDs through a meta-analysis, focusing on key biomarkers including malondialdehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α).

Methods

We searched four databases for studies reporting serum, plasma, or urinary LPO levels in patients with AIDs and healthy controls. Standardized mean differences (SMDs) were pooled using a random-effects model.

Results

Across 175 studies (8227 patients; 6866 controls), serum/plasma MDA levels were significantly elevated in all ten investigated AIDs: rheumatoid arthritis (RA) (SMD = 2.82), systemic sclerosis (SSc) (SMD = 2.08), Graves' disease (GD) (SMD = 1.92), Behçet's disease (BD) (SMD = 1.90), Crohn's disease (CD) (SMD = 1.71), multiple sclerosis (MS) (SMD = 1.52), psoriasis (PsO) (SMD = 1.44), ulcerative colitis (UC) (SMD = 1.32), systemic lupus erythematosus (SLE) (SMD = 1.20) and type 1 diabetes mellitus (T1DM) (SMD = 1.12). Disease-specific elevations were found for serum/plasma 8-iso-PGF2α and 4-hydroxynonenal in RA, urinary 8-iso-PGF2α in SSc and T1DM, and serum/plasma oxidized low-density lipoprotein in T1DM. MDA was higher in active or severe subgroups, with significant between-subgroup differences in GD and PsO.

Conclusion

This meta-analysis provides robust, large-scale clinical evidence that elevated lipid peroxidation is a common feature across diverse AIDs. These findings solidify the clinical relevance of ferroptosis, positioning LPO products as promising biomarkers and underscoring the therapeutic potential of targeting ferroptosis in autoimmune conditions.

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自身免疫性疾病中脂质过氧化生物标志物升高：系统综述和荟萃分析

背景：铁凋亡是一种由脂质过氧化（LPO）驱动的铁依赖性细胞死亡途径，与自身免疫性疾病（艾滋病）的发病机制有关。然而，目前还缺乏全面的临床证据来证明特异性LPO生物标志物与艾滋病之间的联系。目的：以丙二醛（MDA）和8-异前列腺素F2α (8-isoPGF2α)等关键生物标志物为指标，通过meta分析系统评价LPO升高在主要艾滋病患者中的临床证据。方法：我们检索了四个数据库，以报道艾滋病患者和健康对照者的血清、血浆或尿LPO水平。标准化平均差异（SMDs）采用随机效应模型进行汇总。结果：175项研究(8227例患者；6866控制),血清/血浆MDA水平显著升高10艾滋病调查:类风湿性关节炎(RA) (SMD = 2.82),系统性硬化症(SSc) (SMD = 2.08),格雷夫斯氏病(GD) (SMD = 1.92),遗传病的疾病(BD) (SMD = 1.90),克罗恩病(CD) (SMD = 1.71),多发性硬化症(MS) (SMD = 1.52),牛皮癣(PsO) (SMD = 1.44),溃疡性结肠炎(UC) (SMD = 1.32),系统性红斑狼疮(SLE) (SMD = 1.20)和1型糖尿病(T1DM) (SMD = 1.12)。RA患者血清/血浆8-isoPGF2α和4-羟基烯醛升高，SSc和T1DM患者尿8-isoPGF2α升高，T1DM患者血清/血浆氧化低密度脂蛋白升高。MDA在活跃或严重亚组中较高，GD和PsO在亚组间差异显著。结论：这项荟萃分析提供了强有力的、大规模的临床证据，表明脂质过氧化水平升高是各种艾滋病的共同特征。这些发现巩固了铁下垂的临床相关性，将LPO产品定位为有前途的生物标志物，并强调了针对自身免疫性疾病的铁下垂的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Autoimmunity reviews 医学-免疫学

CiteScore

24.70

自引率

4.40%

发文量

164

审稿时长

21 days

期刊介绍： Autoimmunity Reviews is a publication that features up-to-date, structured reviews on various topics in the field of autoimmunity. These reviews are written by renowned experts and include demonstrative illustrations and tables. Each article will have a clear "take-home" message for readers. The selection of articles is primarily done by the Editors-in-Chief, based on recommendations from the international Editorial Board. The topics covered in the articles span all areas of autoimmunology, aiming to bridge the gap between basic and clinical sciences. In terms of content, the contributions in basic sciences delve into the pathophysiology and mechanisms of autoimmune disorders, as well as genomics and proteomics. On the other hand, clinical contributions focus on diseases related to autoimmunity, novel therapies, and clinical associations. Autoimmunity Reviews is internationally recognized, and its articles are indexed and abstracted in prestigious databases such as PubMed/Medline, Science Citation Index Expanded, Biosciences Information Services, and Chemical Abstracts.