硬皮病和狼疮中的抗Ephrin B型受体2（EphB2）和抗3′组蛋白mRNA外切核酸酶1（THEX1）自身抗体
Anti-Ephrin Type-B Receptor 2 (EphB2) and Anti-Three Prime Histone mRNA EXonuclease 1 (THEX1) Autoantibodies in Scleroderma and Lupus.
作者信息
Azzouz Doua F, Martin Gabriel V, Arnoux Fanny, Balandraud Nathalie, Martin Thierry, Dubucquoi Sylvain, Hachulla Eric, Farge-Bancel Dominique, Tiev Kiet, Cabane Jean, Bardin Nathalie, Chiche Laurent, Martin Marielle, Caillet Eléonore C, Kanaan Sami B, Harlé Jean Robert, Granel Brigitte, Diot Elisabeth, Roudier Jean, Auger Isabelle, Lambert Nathalie C
机构信息
INSERM UMRs 1097, Parc Scientifique de Luminy, Marseille, France.
Aix Marseille Université, Marseille, France.
出版信息
PLoS One. 2016 Sep 12;11(9):e0160283. doi: 10.1371/journal.pone.0160283. eCollection 2016.
In a pilot ProtoArray analysis, we identified 6 proteins out of 9483 recognized by autoantibodies (AAb) from patients with systemic sclerosis (SSc). We further investigated the 6 candidates by ELISA on hundreds of controls and patients, including patients with Systemic Lupus Erythematosus (SLE), known for high sera reactivity and overlapping AAb with SSc. Only 2 of the 6 candidates, Ephrin type-B receptor 2 (EphB2) and Three prime Histone mRNA EXonuclease 1 (THEX1), remained significantly recognized by sera samples from SSc compared to controls (healthy or with rheumatic diseases) with, respectively, 34% versus 14% (P = 2.10-4) and 60% versus 28% (P = 3.10-8). Above all, EphB2 and THEX1 revealed to be mainly recognized by SLE sera samples with respectively 56%, (P = 2.10-10) and 82% (P = 5.10-13). As anti-EphB2 and anti-THEX1 AAb were found in both diseases, an epitope mapping was realized on each protein to refine SSc and SLE diagnosis. A 15-mer peptide from EphB2 allowed to identify 35% of SLE sera samples (N = 48) versus only 5% of any other sera samples (N = 157), including SSc sera samples. AAb titers were significantly higher in SLE sera (P<0.0001) and correlated with disease activity (p<0.02). We could not find an epitope on EphB2 protein for SSc neither on THEX1 for SSc or SLE. We showed that patients with SSc or SLE have AAb against EphB2, a protein involved in angiogenesis, and THEX1, a 3'-5' exoribonuclease involved in histone mRNA degradation. We have further identified a peptide from EphB2 as a specific and sensitive tool for SLE diagnosis.
在一项初步的ProtoArray分析中，我们从系统性硬化症（SSc）患者的自身抗体（AAb）识别的9483种蛋白质中鉴定出了6种蛋白质。我们通过酶联免疫吸附测定（ELISA）对数百名对照者和患者（包括系统性红斑狼疮（SLE）患者，SLE以血清高反应性和与SSc重叠的自身抗体而闻名）进一步研究了这6种候选蛋白质。与对照者（健康者或患有风湿性疾病者）相比，这6种候选蛋白质中只有2种，即Ephrin B型受体2（EphB2）和3′端组蛋白mRNA外切核酸酶1（THEX1），仍被SSc患者的血清样本显著识别，识别率分别为34%对14%（P = 2×10⁻⁴）和60%对28%（P = 3×10⁻⁸）。最重要的是，EphB2和THEX1主要被SLE血清样本识别，识别率分别为56%（P = 2×10⁻¹⁰）和82%（P = 5×10⁻¹³）。由于在两种疾病中均发现了抗EphB2和抗THEX1自身抗体，因此对每种蛋白质进行了表位作图以完善SSc和SLE的诊断。来自EphB2的一个15聚体肽能够识别35%的SLE血清样本（N = 48），而在包括SSc血清样本在内的任何其他血清样本（N = 157）中仅能识别5%。SLE血清中的自身抗体滴度显著更高（P<0.0001），并且与疾病活动度相关（P<0.02）。我们在EphB2蛋白上未找到针对SSc的表位，在THEX1上也未找到针对SSc或SLE的表位。我们发现SSc或SLE患者具有针对EphB2（一种参与血管生成的蛋白质）和THEX1（一种参与组蛋白mRNA降解的3′-5′外切核糖核酸酶）的自身抗体。我们进一步鉴定出一种来自EphB2的肽，作为SLE诊断的一种特异性和敏感性工具。
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