Investigation of three potential autoantibodies in Sjogren's syndrome and associated MALT lymphoma.
Investigation of three potential autoantibodies in Sjogren's syndrome and associated MALT lymphoma.
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DOI：
10.18632/oncotarget.15613
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发表时间：
2017-05-02
期刊：
影响因子：
--
通讯作者：
Hu S
中科院分区：
文献类型：
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作者：
Cui L;Elzakra N;Xu S;Xiao GG;Yang Y;Hu S
原发性干燥综合征（pSS）是一种慢性自身免疫性疾病，可发展为粘膜相关淋巴组织淋巴瘤（pSS/MALT）。pSS的诊断需要侵入性组织活检，并且经常报告pSS的诊断延迟。本研究通过双向电泳/质谱分析，发现在pSS和pSS/MALT中有4种蛋白质（cofilin-1，alpha-烯醇化酶，annexin A2和Rho GDP-解离抑制因子2（RGI 2））的过表达，并通过基因芯片分析和蛋白质印迹分析证实了这一发现。然后，我们开发了酶联免疫吸附试验的自身抗体，包括抗cofilin-1，抗α-烯醇化酶和抗RGI 2具有良好的定量能力。唾液中抗cofilin-1、抗α-烯醇化酶和抗RGI 2的表达水平在pSS/MALT患者中最高，在健康对照中最低。这三种抗抗体的组合产生0.94的“曲线下面积”（AUC）值，在区分患有pSS的患者与健康对照中具有86%的灵敏度和93%的特异性，AUC值为0.99，区分pSS/MALT患者与健康对照的灵敏度为95%，特异性为94%，AUC值为0.86，区分pSS/MALT患者与健康对照的灵敏度为75%，特异性为94%。在区分pSS/MALT患者与pSS患者方面的敏感性和94%特异性。总的来说，我们已经成功地确定了一组潜在的自身抗原，这些抗原在pSS的发展及其向MALT淋巴瘤的进展过程中逐渐上调。自身抗体生物标志物可用于帮助诊断pSS并预测其向MALT淋巴瘤的进展。
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease which might progress to mucosal-associated lymphoid tissue lymphoma (pSS/MALT). Diagnosis of pSS requires an invasive tissue biopsy and a delay in diagnosis of pSS has been frequently reported. In this study, four proteins including cofilin-1, alpha-enolase, annexin A2 and Rho GDP-dissociation inhibitor 2 (RGI2) were found to be over-expressed in pSS and pSS/MALT by 2D gel electrophoresis/mass spectrometry, and the finding was verified by the microarray analysis and western blotting results. We then developed enzyme-linked immunosorbent assays for autoantibodies including anti-cofilin-1, anti-alpha-enolase and anti-RGI2 with good quantitative ability. The expression levels of salivary anti-cofilin-1, anti-alpha-enolase and anti-RGI2 were found to be the highest in pSS/MALT patients and lowest in healthy controls. The combination of these three antiantibodies yielded an “area under the curve” (AUC) value of 0.94 with an 86% sensitivity and 93% specificity in distinguishing patients with pSS from healthy controls, an AUC value of 0.99 with a 95% sensitivity and 94% specificity in distinguishing patients with pSS/MALT from healthy controls and an AUC value of 0.86 with a 75% sensitivity and 94% specificity in distinguishing pSS/MALT patients from pSS patients. Collectively, we have successfully identified a panel of potential autoantigens that are progressively up-regulated during the development of pSS and its progression to MALT lymphoma. The autoantibody biomarkers may be used to help diagnose pSS and predict its progression to MALT lymphoma.