Patients with systemic lupus erythematosus (SLE) have a circulating inducer of interferon‐alpha (IFN‐α) production acting on leucocytes resembling immature dendritic cells
Patients with systemic lupus erythematosus (SLE) have a circulating inducer of interferon‐alpha (IFN‐α) production acting on leucocytes resembling immature dendritic cells
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DOI：
10.1046/j.1365-2249.1999.00772.x
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发表时间：
1999-01
影响因子：
4.6
通讯作者：
H. Vallin;S. Blomberg;G. Alm;B. Cederblad;L. Rönnblom
中科院分区：
文献类型：
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作者：
H. Vallin;S. Blomberg;G. Alm;B. Cederblad;L. Rönnblom
活动期系统性红斑狼疮患者通常会持续产生干扰素-α。因此，我们在系统性红斑狼疮患者中寻找内源性干扰素-α诱导因子，发现他们的血清经常诱导健康献血者外周血单核细胞培养产生干扰素-α，特别是当细胞因子干扰素-α2b和粒-巨噬细胞集落刺激因子(GM-CSF)共刺激外周血单个核细胞时。流式细胞仪检测结果显示，干扰素-α产生细胞的表型与天然细胞一致，类似于未成熟的树突状细胞。系统性红斑狼疮患者血清中干扰素的活性有时与病毒一样高，尤其在活动期疾病患者和血清中干扰素-α水平可测的患者中存在。IIF的表观分子量为300-1000kD，似乎由免疫球蛋白和DNA组成，可能是免疫复合体。这种内源性干扰素-α诱导剂可能具有致病意义，因为据报道，干扰素-α治疗非自身免疫性疾病患者偶尔会出现抗双链DNA抗体和系统性红斑狼疮的不良反应。
Patients with active SLE often have an ongoing production of IFN‐α. We therefore searched for an endogenous IFN‐α‐inducing factor (IIF) in SLE patients and found that their sera frequently induced production of IFN‐α in cultures of peripheral blood mononuclear cells (PBMC) from healthy blood donors, especially when the PBMC were costimulated with the cytokines IFN‐α2b and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). The phenotype of the IFN‐α‐producing cells (IPC) as determined by flow cytometry corresponded to that of the natural IPC, resembling immature dendritic cells. The IIF activity in SLE sera was sometimes as high as that of a virus and was present especially in patients with active disease and with measurable IFN‐α levels in serum. The IIF had an apparent molecular weight of 300–1000 kD and appeared to consist of both immunoglobulin and DNA, possibly being immune complexes. This endogenous IFN‐α inducer may be of pathogenic significance, since a reported occasional adverse effect of IFN‐α therapy in patients with non‐autoimmune disorders is development of anti‐dsDNA antibodies and SLE.