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首页> 外文期刊>Rheumatology >Influence of human recombinant interferon-alpha2a (rhIFN-alpha2a) on altered lymphocyte subpopulations and monocytes in Behcet's disease.
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Influence of human recombinant interferon-alpha2a (rhIFN-alpha2a) on altered lymphocyte subpopulations and monocytes in Behcet's disease.

机译:人重组干扰素-α2a(rhIFN-α2a)对白塞病患者淋巴细胞亚群和单核细胞改变的影响。

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OBJECTIVE: In Behcet's disease (BD), several abnormalities of lymphocyte subpopulations have been described. Standard treatment comprises immunosuppressive drugs. We successfully treated 50 patients with ocular BD with interferon-alpha2a (IFN-alpha2a) (response rate 92%), although this is counterintuitive because IFN-alpha is immunostimulatory and can sometimes even induce autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis. The aim of the present study was to elucidate the immunomodulatory effects that IFN-alpha might exert on peripheral blood mononuclear cells (PBMC) in BD by examining changes in the distribution of lymphocyte subpopulations under IFN-alpha2a treatment. METHODS: Fourteen patients with ocular BD were evaluated before and at weeks 4 and 24 of IFN-alpha treatment and compared with 10 healthy controls. PBMC were stained with monoclonal antibodies and measured by flow cytometry. RESULTS: Compared with the controls there is a significant elevation of monocytes (CD14(+)), CD8(+)/gammadelta T cells, CD3(+)/gammadelta T cells, natural killer (NK) cells (CD56(+)/CD16(+)) and activated/regulatory T cells (CD4(+)/CD25(+) and CD8(+)/CD25(+)) in patients with active BD before treatment with IFN-alpha2a. Numbers of naive T cells (CD8(+)/CD45(+)RA(+)/RO(-), CD4(+)/CD45(+)RA(+)/RO(-)) were significantly lower. Under therapy, NK cells, CD8(+)/gammadelta T cells and CD3(+)/gammadelta T cells decreased significantly, whereas B cells increased. The previously reduced expression of HLA class I on monocytes in HLA-B51-positive patients rose to levels comparable to HLA-B51-negative patients. CONCLUSION: These results implicate the participation of NK cells and gammadelta T cells, especially CD8(+)/gammadelta T cells, in the pathogenesis of BD and may explain one mechanism by which IFN-alpha2a exerts therapeutic effects. Alternatively, they may result indirectly from remission induction by IFN-alpha2a. The reduced expression of HLA class I on monocytes in HLA-B*51-positive patients might reflect an impaired expression of and antigen presentation by HLA-B*51.
机译:目的:在白塞氏病(BD)中,已经描述了几种淋巴细胞亚群异常。标准治疗包括免疫抑制药物。我们成功地用干扰素-α2a(IFN-α2a)治疗了50例眼部BD患者(反应率92%),尽管这是违反直觉的,因为IFN-α具有免疫刺激作用,有时甚至可以诱发自身免疫性疾病,例如系统性红斑狼疮或类风湿性关节炎。本研究的目的是通过检查在IFN-alpha2a处理下淋巴细胞亚群分布的变化,阐明IFN-α可能对BD外周血单个核细胞(PBMC)发挥的免疫调节作用。方法:在IFN-α治疗的第4周和第24周以及治疗第4周和第24周对14例眼部BD患者进行了评估,并与10名健康对照者进行了比较。 PBMC用单克隆抗体染色,并通过流式细胞仪进行测量。结果:与对照组相比,单核细胞(CD14(+)),CD8(+)/γT细胞,CD3(+)/γT细胞,自然杀伤(NK)细胞(CD56(+)/ CD16(+))和活化/调节性T细胞(CD4(+)/ CD25(+)和CD8(+)/ CD25(+))在患有BD的患者中接受IFN-alpha2a治疗之前。幼稚T细胞(CD8(+)/ CD45(+)RA(+)/ RO(-),CD4(+)/ CD45(+)RA(+)/ RO(-)的数量明显减少。在治疗下,NK细胞,CD8(+)/γT细胞和CD3(+)/γT细胞明显减少,而B细胞增加。 HLA-B51阳性患者先前在单核细胞上减少的HLA I类表达上升至与HLA-B51阴性患者相当的水平。结论:这些结果暗示了NK细胞和γT细胞,特别是CD8(+)/γT细胞参与BD的发病机制,并可能解释了IFN-α2a发挥治疗作用的一种机制。或者,它们可能是由IFN-α2a诱导的缓解间接导致的。 HLA-B * 51阳性患者单核细胞上HLA I类表达的减少可能反映了HLA-B * 51的表达受损和抗原呈递。

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