α-辅肌动蛋白结合抗双链DNA抗体与狼疮性肾炎的关联。

Association of alpha-actinin-binding anti-double-stranded DNA antibodies with lupus nephritis.

作者信息

Renaudineau Yves, Croquefer Sabine, Jousse Sandrine, Renaudineau Eric, Devauchelle Valérie, Guéguen Paul, Hanrotel Catherine, Gilburd Boris, Saraux Alain, Shoenfeld Yehuda, Putterman Chaim, Youinou Pierre

机构信息

Brest University Medical School, Brest, France.

出版信息

Arthritis Rheum. 2006 Aug;54(8):2523-32. doi: 10.1002/art.22015.

DOI:10.1002/art.22015

PMID:16868973

Abstract

OBJECTIVE

Anti-double-stranded DNA (anti-dsDNA) antibodies may contribute to the pathogenesis of glomerulonephritis (GN) by cross-reacting with alpha-actinin in murine models and in some patients with systemic lupus erythematosus (SLE). We therefore sought to determine possible disease associations with serologic and clinical features and to characterize this new autoantibody specificity.

METHODS

One hundred patients with SLE were recruited into this multicenter study, as well as 100 rheumatic disease controls and 2,100 healthy blood donors. Clinical disease was evaluated by the SLE Disease Activity Index (SLEDAI; excluding the anti-DNA component). Anti-dsDNA antibodies were detected by conventional enzyme-linked immunosorbent assay (ELISA) and by a commercial enzyme immunoassay (EIA). Anti-alpha-actinin antibodies were detected by ELISA, and their specificity was confirmed by Western blotting and by indirect immunofluorescence using rat kidney sections and mesangial cells as substrates. Highly positive sera were selected for absorption experiments and were affinity-purified for cross-reactivity studies and measurement of antibody avidity.

RESULTS

Sera from 62 of the SLE patients had anti-dsDNA antibodies; 21 of these sera also had anti-alpha-actinin antibodies, as compared with 1 of the 38 sera without anti-dsDNA antibodies. Of the 22 patients with anti-alpha-actinin antibodies, 10 had GN, as compared with 14 of the 78 without anti-alpha-actinin antibodies (P < 0.01). In patients with GN, anti-alpha-actinin, but not anti-dsDNA, antibodies correlated with the SLEDAI score (minus the anti-DNA component) and with treatment. The fraction of serum anti-dsDNA antibodies that cross-reacted with alpha-actinin exhibited high avidity for dsDNA, as determined using a commercial EIA for high-avidity anti-dsDNA antibodies and an in-house conventional ELISA.

CONCLUSION

The alpha-actinin-binding antibodies are significantly associated with GN in SLE. Whether such autoantibodies may anticipate the development of this complication of SLE remains to be verified.

摘要

目的

在小鼠模型以及部分系统性红斑狼疮（SLE）患者中，抗双链DNA（anti-dsDNA）抗体可通过与α-辅肌动蛋白发生交叉反应，进而参与肾小球肾炎（GN）的发病机制。因此，我们试图确定这种新的自身抗体特异性与血清学及临床特征之间可能存在的疾病关联，并对其进行特征描述。

方法

本多中心研究纳入了100例SLE患者、100例风湿性疾病对照者以及2100例健康献血者。通过SLE疾病活动指数（SLEDAI；不包括抗DNA成分）评估临床疾病情况。采用传统酶联免疫吸附测定（ELISA）和一种商业酶免疫测定（EIA）检测抗dsDNA抗体。通过ELISA检测抗α-辅肌动蛋白抗体，并使用大鼠肾脏切片和系膜细胞作为底物，通过蛋白质印迹法和间接免疫荧光法确认其特异性。选择高阳性血清进行吸收实验，并进行亲和纯化以进行交叉反应研究和抗体亲和力测定。

结果

62例SLE患者的血清中有抗dsDNA抗体；其中21例血清也有抗α-辅肌动蛋白抗体，而38例无抗dsDNA抗体的血清中只有1例有该抗体。在22例有抗α-辅肌动蛋白抗体的患者中，10例患有GN，而78例无抗α-辅肌动蛋白抗体的患者中有14例患有GN（P<0.01）。在患有GN的患者中，抗α-辅肌动蛋白抗体而非抗dsDNA抗体与SLEDAI评分（减去抗DNA成分）及治疗相关。使用一种用于检测高亲和力抗dsDNA抗体的商业EIA和一种内部传统ELISA测定，与α-辅肌动蛋白发生交叉反应的血清抗dsDNA抗体部分对dsDNA表现出高亲和力。