Amara A, Constans J, Chaugier C, Sebban A, Dubourg L, Peuchant E, Pellegrin J L, Leng B, Conri C, Geffard M
Laboratoire d'Immunologie, Université de Bordeaux II, France.
Clin Exp Immunol. 1995 Aug;101(2):233-8. doi: 10.1111/j.1365-2249.1995.tb08344.x.
Malondialdehyde (MDA), a peroxidative end-product released during polyunsaturated fatty acid degradation, reacts strongly with lysine residues of cellular proteins. MDA-modified proteins become immunogenic and may elicit specific autoantibody formation. We hypothesized that systemic diseases in which inflammatory events occur, could be an interesting model for studying oxidative stress. A few studies have suggested that MDA-modified proteins may exist in systemic diseases, and that autoantibodies to MDA-modified structures might reflect this oxidative process. Autoantibodies to MDA-modified epitope(s) were therefore assayed in sera of patients with systemic lupus erythematosus (SLE, n = 29), scleroderma (SCL, n = 11), giant cell arteritis (GCA, n = 11), periarteritis nodosa (PAN, n = 10), rheumatoid arthritis (RA, n = 9), and healthy subjects (HS, n = 32). Significantly increased anti-MDA-modified epitope(s) autoantibodies were found in patients with SLE and also in other systemic diseases such as PAN and SCL. Autoantibodies to MDA-modified epitope(s) were predominantly of IgM isotype, with low levels of IgG and no IgA activity. In SLE, anti-MDA-modified epitope(s) autoantibody titres correlated strongly with systemic lupus activity measure (SLAM, r = 0.702, P = 0.0001), anti-nuclear antigen autoantibodies (ANA, r = 0.4, P = 0.029), IgG anti-cardiolipin (r = 0.558, P = 0.03) and the steroid drug regimen (r = 0.52, P = 0.004). Autoantibodies to MDA-modified epitope(s) may reflect oxidative modifications occurring in systemic diseases, and might be useful as clinical markers of SLE activity if further investigated.
丙二醛（MDA）是多不饱和脂肪酸降解过程中释放的一种过氧化终产物，它与细胞蛋白的赖氨酸残基发生强烈反应。MDA修饰的蛋白具有免疫原性，可能引发特异性自身抗体的形成。我们推测，发生炎症事件的全身性疾病可能是研究氧化应激的一个有趣模型。一些研究表明，MDA修饰的蛋白可能存在于全身性疾病中，针对MDA修饰结构的自身抗体可能反映了这种氧化过程。因此，我们检测了系统性红斑狼疮（SLE，n = 29）、硬皮病（SCL，n = 11）、巨细胞动脉炎（GCA，n = 11）、结节性多动脉炎（PAN，n = 10）、类风湿关节炎（RA，n = 9）患者以及健康受试者（HS，n = 32）血清中针对MDA修饰表位的自身抗体。结果发现，SLE患者以及PAN和SCL等其他全身性疾病患者中，抗MDA修饰表位自身抗体显著增加。针对MDA修饰表位的自身抗体主要为IgM同种型，IgG水平较低，无IgA活性。在SLE中，抗MDA修饰表位自身抗体滴度与系统性红斑狼疮活动度测量指标（SLAM，r = 0.702，P = 0.0001）、抗核抗原自身抗体（ANA，r = 0.4，P = 0.029）、IgG抗心磷脂抗体（r = 0.558，P = 0.03）以及类固醇药物治疗方案（r = 0.52，P = 0.004）密切相关。针对MDA修饰表位的自身抗体可能反映全身性疾病中发生的氧化修饰，如果进一步研究，可能作为SLE活动度的临床标志物。
