Janssen Pharmaceutical Research & Development, L.L.C., Innate Immunity, Spring House, PA 19477, United States.
Cell Immunol. 2013 Jul-Aug;284(1-2):119-28. doi: 10.1016/j.cellimm.2013.07.017. Epub 2013 Aug 6.
Plasmacytoid dendritic cells [pDC], also known as type I interferon [IFN] producing cells, play a significant role in the pathogenesis of systemic lupus erythematosus [SLE]. The current study was undertaken to identify novel SLE autoantibody specificities associated with interferon-inducing activity in human pDCs. We found that immune complex mixtures from some Interferon signature negative [IFN-] and all interferon signature positive [IFN+] SLE patients could trigger type I IFN production by pDCs. IgGs from IFN- and IFN+ SLE patients were subsequently screened via a high throughput protein microarray to identify novel auto-antibody specifities that mediate type I IFN production by pDCs. This approach identified five novel autoantibodies that may contribute to type I IFN production by pDCs via a nucleic acid dependent mechanism. The newly identified autoantibody specificities function in a myriad of cell processess and, to date, have not been implicated in SLE pathogenesis.
浆细胞样树突状细胞 [pDC]，也称为 I 型干扰素 [IFN] 产生细胞，在系统性红斑狼疮 [SLE] 的发病机制中发挥重要作用。本研究旨在鉴定与人类 pDC 中干扰素诱导活性相关的新型 SLE 自身抗体特异性。我们发现，一些干扰素特征阴性 [IFN-] 和所有干扰素特征阳性 [IFN+] SLE 患者的免疫复合物混合物可触发 pDC 产生 I 型 IFN。随后，通过高通量蛋白质微阵列筛选 IFN- 和 IFN+ SLE 患者的 IgG，以鉴定通过 pDC 介导 I 型 IFN 产生的新型自身抗体特异性。该方法鉴定了五种新型自身抗体，它们可能通过核酸依赖机制促进 pDC 产生 I 型 IFN。新鉴定的自身抗体特异性在多种细胞过程中发挥作用，迄今为止尚未涉及 SLE 的发病机制。
