5C11 阳性活化的干扰素产生细胞在系统性红斑狼疮患者中的特征。

Characterization of 5C11-positive activated interferon-producing cells in patients with systemic lupus erythematosus.

机构信息

Department of Allergy and Rheumatology, University of Tokyo, Japan.

出版信息

Lupus. 2013 Jan;22(1):44-51. doi: 10.1177/0961203312463620. Epub 2012 Oct 19.

DOI:10.1177/0961203312463620

PMID:23087259

Abstract

OBJECTIVE

5C11 antibody is a novel monoclonal antibody against human BST2 and can be used to detect activation of interferon-producing cells (IPCs). Activated IPCs, which produce large amounts of interferon-α (IFNα), are considered to play an important role in the pathogenesis of systemic lupus erythematosus (SLE). We investigated the characterization of 5C11-positive cells in patients with SLE.

METHODS

The proportions of 5C11-positive cells among blood dendritic cell antigen 2 (BDCA-2)-, CD3-, CD19- and CD14-positive cells in peripheral blood from SLE patients (SLE-PBMCs) and healthy controls (control-PBMCs) were analyzed by flow cytometry. The effect of 5C11 antibody on IFNα production from SLE-PBMCs under stimulation with cytosine-phosphate-guanosine (CpG2216, bacterial oligonucleotide motif) was also examined by enzyme-linked immunosorbent assay (ELISA).

RESULTS

The proportions of 5C11-positive cells among BDCA-2-, CD3- and CD19-, but not CD14-positive cells in SLE-PBMCs were significantly increased compared to those in control-PBMCs (p < 0.0001, all). Especially, the number of 5C11-positive cells among BDCA-2-positive cells was significantly increased in SLE-PBMCs by about six-fold compared to that in control-PBMCs (p < 0.0001). 5C11 antibody inhibited IFNα production by SLE-PBMCs induced by CpG and the inhibition rates was 27% (p < 0.001).

CONCLUSION

SLE patients had a significantly higher proportion of 5C11-positive cells among CD3 and CD19 cells, and especially BDCA-2 positive cells. The ability of 5C11 antibody to inhibit IFNα production from SLE-PBMCs warrants further investigation for its possible clinical application for the treatment of SLE.

摘要

目的

5C11 抗体是一种针对人 BST2 的新型单克隆抗体，可用于检测干扰素产生细胞（IPC）的激活。活化的 IPC 会产生大量干扰素-α（IFNα），被认为在系统性红斑狼疮（SLE）的发病机制中发挥重要作用。我们研究了 SLE 患者中 5C11 阳性细胞的特征。

方法

通过流式细胞术分析 SLE 患者（SLE-PBMCs）和健康对照者（control-PBMCs）外周血中树突状细胞抗原 2（BDCA-2）、CD3、CD19 和 CD14 阳性细胞中 5C11 阳性细胞的比例。还通过酶联免疫吸附试验（ELISA）检测 5C11 抗体对 SLE-PBMCs 在胞嘧啶磷酸鸟嘌呤（CpG2216，细菌寡核苷酸基序）刺激下产生 IFNα 的影响。

结果

与 control-PBMCs 相比，SLE-PBMCs 中 5C11 阳性细胞在 BDCA-2、CD3 和 CD19 阳性细胞中的比例显著增加（p<0.0001，均）。特别是，SLE-PBMCs 中 5C11 阳性细胞在 BDCA-2 阳性细胞中的数量比 control-PBMCs 增加了约六倍（p<0.0001）。5C11 抗体抑制了 CpG 诱导的 SLE-PBMCs 产生 IFNα，抑制率为 27%（p<0.001）。