Distinct Autoantibody Profiles in Systemic Lupus Erythematosus Patients are Selectively Associated with TLR7 and TLR9 Upregulation
Distinct Autoantibody Profiles in Systemic Lupus Erythematosus Patients are Selectively Associated with TLR7 and TLR9 Upregulation
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DOI：
10.1007/s10875-013-9887-0
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发表时间：
2013-07-01
影响因子：
9.1
通讯作者：
Rai, Geeta
中科院分区：
文献类型：
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作者：
Chauhan, Sudhir Kumar;Singh, Vikas Vikram;Rai, Geeta
目的系统性红斑狼疮（SLE）患者体内存在多种抗核抗原的自身抗体。这些自身抗体的两个主要类别针对dsDNA或RNA相关抗原（可提取的核抗原; ENA）。识别双链DNA和RNA的核酸传感Toll样受体（TLR）在一些SLE小鼠模型中有很好的应用。我们进行了这项研究，以确定是否独特的TLR表达模式与不同的自身抗体在SLE.Methods公司，我们将患者分为三个子集区分的基础上，无论是对dsDNA或ENA或两者的自身抗体反应。我们通过实时逆转录PCR测定了所有三个子集的SLE患者外周血白细胞（PBL）中TLR 3、7、8和9的mRNA表达。TLR 7和9蛋白表达通过PBL中的蛋白质印迹和通过B细胞和单核细胞上的流式细胞术测定。采用酶联免疫吸附试验检测血清干扰素-α（IFN-α）和抗dsDNA/-ENA自身抗体。SLE患者中抗ENA和抗dsDNA自身抗体的存在分别与TLR 7和TLR 9水平升高相关。SLE合并肾小球肾炎患者TLR 9 mRNA表达进一步增强。抗dsDNA（+）ENA（+）患者血清IFN α和IFN调节因子7 mRNA表达水平高于抗dsDNA或抗ENA自身抗体阳性患者。
Purpose Systemic lupus erythematosus (SLE) patients have a wide array of autoantibodies against nuclear antigens. The two predominant classes of these autoantibodies are directed either against dsDNA or RNA-associated antigens (extractable nuclear antigens; ENA). Nucleic-acid sensing Toll-like receptors (TLRs) that recognize dsDNA and RNA, have been well implicated in some murine models of SLE. We took up this study to identify if unique TLR expression patterns are associated with distinct autoantibody profiles in SLE.Methods We segregated the patients into three subsets distinguished on the basis of autoantibody response either against dsDNA or ENA or both. We determined the mRNA expression of TLR3, 7, 8, and 9 by real-time reverse-transcription PCR in peripheral blood leucocytes (PBLs) of the SLE patients of all three subsets. TLR7 and 9 protein expression was determined by western blotting in PBLs and by flow cytometry on B-cells and monocytes. The serum interferon-alpha (IFN-alpha) and anti-dsDNA/-ENA autoantibodies were detected using enzyme-linked immunosorbant assay.Results We report differential and unique TLR expression patterns associated with different autoantibody profiles. The presence of anti-ENA and anti-dsDNA autoantibodies in SLE patients was associated with elevated levels of TLR7 and TLR9 respectively. The TLR9 mRNA expression was further augmented in SLE patients with Glomerulonephritis. Interestingly, anti-dsDNA(+) ENA(+) patients displayed higher serum IFN-alpha and interferon regulatory factor 7 mRNA expression than patients with either anti-dsDNA or anti-ENA autoantibodies alone.Conclusion Characteristic TLRs expression profile associated with distinct autoantibody repertoire is suggestive of differential immuno-regulatory pathways operative in different subsets of SLE patients.