Zhuang Haoyang, Kosboth Mona, Lee Pui, Rice Amanda, Driscoll Daniel J, Zori Roberto, Narain Sonali, Lyons Robert, Satoh Minoru, Sobel Eric, Reeves Westley H
University of Florida, Gainesville, USA.
Arthritis Rheum. 2006 May;54(5):1573-9. doi: 10.1002/art.21800.
Systemic lupus erythematosus (SLE) is associated with type I interferons (IFNs) and can be induced by IFNalpha treatment. This study looked for evidence of autoimmunity in a pedigree consisting of 4 family members with a balanced translocation 9;21 and 2 members with an unbalanced translocation resulting in trisomy of the short (p) arm and part of the long (q) arm of chromosome 9. These latter 2 subjects had 3 copies of the IFN gene cluster.
Subjects were evaluated clinically and serologically for autoimmune disease. Expression levels of IFNalpha4, IFNbeta, the type I IFN-inducible gene Mx1, the type I IFN receptor, interleukin-6, and tumor necrosis factor alpha were determined by real-time polymerase chain reaction. Circulating plasmacytoid dendritic cells, the main IFN-producing cells, were quantified by flow cytometry.
Both subjects with trisomy of chromosome 9p had a lupus-like syndrome with joint manifestations and antinuclear antibodies: one had anti-RNP and antiphospholipid autoantibodies, and the other had anti-Ro 60. The 3 family members with a balanced translocation 9;21 had no clinical or serologic evidence of autoimmunity, similar to that in relatives who were unaffected by the chromosomal translocation. In the 2 subjects with trisomy of 9p, high levels of IFNalpha/beta (comparable with those found in patients with SLE), increased signaling through the IFN receptor (as indicated by high Mx1 expression), and low levels of circulating plasmacytoid dendritic cells (as observed in patients with SLE) were evident. These abnormalities were not seen in individuals with a balanced translocation.
Trisomy of the type I IFN cluster of chromosome 9p was associated with lupus-like autoimmunity and increased IFNalpha/beta and IFN receptor signaling. The data support the idea that abnormal regulation of type I IFN production is involved in the pathogenesis of SLE.
系统性红斑狼疮（SLE）与Ⅰ型干扰素（IFN）相关，且可由α干扰素治疗诱发。本研究在一个家系中寻找自身免疫的证据，该家系包括4名携带9号与21号染色体平衡易位的家庭成员以及2名携带不平衡易位导致9号染色体短臂（p）和部分长臂（q）三体的成员。后两名受试者有3份IFN基因簇拷贝。
对受试者进行自身免疫性疾病的临床和血清学评估。通过实时聚合酶链反应测定α干扰素4、β干扰素、Ⅰ型干扰素诱导基因Mx1、Ⅰ型干扰素受体、白细胞介素-6和肿瘤坏死因子α的表达水平。通过流式细胞术对主要产生IFN的循环浆细胞样树突状细胞进行定量。
两名9号染色体短臂三体的受试者均患有类似狼疮的综合征，有关节表现和抗核抗体：其中一名有抗核糖核蛋白和抗磷脂自身抗体，另一名有抗Ro 60。3名携带9号与21号染色体平衡易位的家庭成员没有自身免疫的临床或血清学证据，这与未受染色体易位影响的亲属情况类似。在两名9号染色体短臂三体的受试者中，明显存在高水平的α/β干扰素（与SLE患者中发现的水平相当）、通过干扰素受体的信号传导增加（如Mx1高表达所示）以及循环浆细胞样树突状细胞水平低（如SLE患者中观察到的）。这些异常在携带平衡易位的个体中未见到。
9号染色体短臂的Ⅰ型干扰素基因簇三体与类似狼疮的自身免疫以及α/β干扰素和干扰素受体信号传导增加有关。数据支持Ⅰ型干扰素产生的异常调节参与SLE发病机制的观点。
