Immunoadsorbent apheresis eliminates pathogenic IgG in childhood lupus nephritis

BACKGROUND: It is suggested that the highly cation-charged fraction of the IgG and IgG3 subclasses may play a pathogenic role in lupus nephritis. In contrast, immunoadsorbent therapy using a sodium dextransulfate fixed cellulose gel column-low invasive selective immunoadsorbent apheresis therapy (SDSC-IAT) has been applied to lupus nephritis with favorable results. However, elimination using pathogenic IgG by SDSC-IAT has never been investigated. METHOD: Two patients with diffuse proliferative lupus nephritis were treated using SDSC-IAT concomitant with immunosuppressive therapy. The eluates from the SDSC, and the patients' serum obtained before and just after SDSC-IAT were subjected to an IgG charge analysis using isoelectric focusing and immunoblotting, and also to laser nephelometry assay, which is used for measuring IgG subclass concentration. Indirect immunofluorescence staining was performed to detect IgG subclass deposition in the glomerulus. RESULTS: Both of the patients had an immediate decrease in anti-double-strand DNA antibody and in the circulating immune complex with a following clinical improvement. Repeated biopsies demonstrated improvement of glomerular lesions with a marked reduction of IgG and C3 deposition. The IgG of the SDSC eluates consisted of highly cation charged (isoelectric points: 9-10) fractions. In addition, IgG3 was specifically removed from the patients' serum using an SDSC among the IgG subclasses. The subclass of deposited IgG in the glomeruli showed IgG3 predominance. CONCLUSION: SDSC-IAT specifically removed the highly cation charged fractions of IgG and IgG3 from the patients' serum and the elimination of these fractions may have resulted in clinical improvement.     

SLE小鼠高IgG血症Fcgr2b基因序列分析

目的: 测定系统性红斑狼疮(SLE)小鼠模型-NZB/WF1双亲NZB,NZW小鼠 Fcgr2b基因启动子区核酸序列,明确Fcgr2b基因启动子区的突变性质.方法:扩增NZB,NZW小鼠Fcgr2b基因启动子DNA进行核酸序列分析.采用ELISA法测定、比较(NZB×NZW )F1×NZW回交小鼠Fcgr2b基因B/W型与W/W型组间血清总IgG 水平.结果:NZB小鼠Fcgr2b基因启动子区与正常鼠Balb/C相比存在2个部位碱基缺失,分别为13 bp及3 bp.NZW小鼠除有3个碱基置换外,与Balb/C鼠该基因启动子区序列相同.回交小鼠Fcgr2b基因B/W型组血清总 IgG水平明显高于W/W型组(P<0.0001).结论:NZB小鼠Fcgr2b基因启动子区存在碱基缺失,且该缺失突变可能与血清总IgG水平升高有关.     

系统性红斑狼疮肺胸膜病变(附50例报告)

50例SLE患者有肺胸膜病变,其中女性47例(94％),男性3例(6％),小于40岁者41例(82％)。50例中表现为胸膜炎和(或)胸腔积液26例,狼疮肺炎15例,弥漫性肺间质纤维化5例,肺不张3例,肺纹理增多17例。经激素治疗随SLE症状改善,肺胸膜病变好转。     

Phenotypic and genetic analyses of T-cell-mediated immunoregulation in patients with Type 1 diabetes.

AIMS: To investigate the contribution of regulatory T cells and co-stimulatory molecules in CD4(+) T cells to the development of Type 1 diabetes (T1D). METHODS: Twelve patients with T1D, nine patients with systemic lupus erythematosus (SLE), and 12 age-matched healthy control subjects participated. We analysed the proportions of CD25(+)CD4(+) T cells and natural killer T cells (NKT cells), and the expression levels of Foxp3, CTLA-4, CD28, ICOS, PD-1 and BTLA in peripheral blood mononuclear cells and purified CD4(+) T cells. RESULTS: There were no significant differences in the proportions of CD25(+) CD4(+) T cells or NKT cells among the three groups. PD-1 expression levels of peripheral CD4(+) T cells from T1D patients were significantly lower than those from healthy control subjects (P = 0.00066). In contrast, PD-1 expression levels were similar in SLE patients and healthy control subjects. The expression levels of Foxp3, CTLA-4, CD28, ICOS and BTLA were similar in the three groups. CONCLUSIONS: Decreased expression of the PD-1 gene in CD4(+) T cells may contribute to the development and/or maintenance of autoimmune T1D. As the population studied was small and heterogeneous, further studies are required to confirm the findings.     

Monospecific but not polyreactive human hybridoma rheumatoid factors exhibit preferential binding specificities for IgG3 and IgG4

Summary Among 38 human hybridoma-derived monoclonal rheumatoid factors (RFs) generated from patients with either rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE), two groups of RFs can be identified. Monospecific RFs were derived primarily from patients with RA and are characterized by a binding specificity for IgG3 and/or IgG4. Polyreactive RFs were derived largely from patients with SLE and show a broader pattern of reactivity to all four isotypes of IgG. Neither population of RFs was exclusive to either disease. The binding specificities identified appear to be different from the RFs isolated from patients with mixed cryoglobulinemia and may reflect a different antigen selection mechanism.     

COX-2在系统性红斑狼疮病人PBMC中的表达及意义

目的：检测环氧全酶-2(Cyclooxygenase-2，COX-2)蛋白在系统性红斑狼疮(Systemic lupus erythematosus．SLE)患外周血单核细胞(Peripheral blood monoeytes，PBMC)中的表达情况。探讨COX-2蛋白表达水平与SLE病情活动程度之间的关系。方法：从外周血中分离PBMC后涂片，用免疫组化染色的方法测定COX-2蛋白的表达情况。结果：COX-2蛋白在SLE实验组呈高表达状态，与SLE疾病的活动性之间呈正相关。结论：COX-2的表达与SLE的发病有关，可作为今后辅助治疗措施的目标和病情变化和疗效评价的参考指标之-。     

神经精神性红斑狼疮的脑部MRI表现

目的 分析神经精神性红斑狼疮（NP-SLE）的脑部MRI表现,探讨MRI对NP-SLE的诊断价值.方法 收集2000年1月～2005年4月符合NP-SLE临床诊断标准病例13例,均为女性,年龄10～40岁,平均30岁,病程30天～25年.采用Simens Impact 1.0T MR成像仪,SE序列行轴位T1WI、T2WI、矢状位T2WI及增强扫描,分析其脑部MRI表现.结果 13例20次MRI检查均有异常,阳性率为100%,表现为点状、斑片状长T1长T2异常信号,主要分布在大脑皮层、层下白质及基底节区,病灶周围无水肿,占位效应不明显.2例增强扫描病灶呈不规则强化,7例有脑萎缩.结论 MRI对NP-SLE脑部病变有较高的价值,但作出NP-SLE诊断需结合临床和实验室检查.     

Evaluation of the Japanese-Chinese Herbal Medicine,Kampo, for the Treatment of Lupus Dermatoses in Autoimmune Prone MRL/Mp-lpr/lpr Mice

Kampo, a Japanese-Chinese traditional herbal medicine, has been used for the treatment of various diseases for about 3,000 years in China. Among herbal medicines, Sairei-to is well known for improving the symptoms of rheumatoid arthritis (RA) and other collagen diseases. However, its immunosuppressive effects on autoimmune cutaneous phenomena are not completely understood. We investigated the effects of Sairei-to on the development of lupus dermatoses in autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mice, an animal model which spontaneously develops skin lesions similar to those seen in human lupus erythematosus. Virgin female MRL/lpr mice at 1 month of age, which were treated orally with Sairei-to, had reduced amounts of IgG deposition at the dermoepidermal junction, titers of anti-DNA antibodies and rheumatoid factor, and lymphoproliferation. These results support the use of traditional herbal medicines in patients with human RA and systemic lupus erythematosus.