Biomarcadores elevados de peroxidación lipídica en enfermedades autoinmunes: una revisión sistemática y metaanálisis

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.

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-isoprostaglandin F2α (8-isoPGF2α).

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.

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 (T1DM) (SMD = 1.12). Disease-specific elevations were found for serum/plasma 8-isoPGF2α and 4-hydroxynonenal in RA, urinary 8-isoPGF2α 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.

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.