A long duration follow up of childern born to patients With systematic lupus erythematosus (SLE)

对系统性红斑狼疮 (SLE) 患者所生子女的长期随访

• 批准号: 09470128
• 负责人: HASHIMOTO Hiroshi
• 金额: $ 3.39万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470128/
• 关键词: SLE; HLA-classll; children; antinuclear antibodies; CD80; CD86; Fas; B cell; T cell; HLA-class II; 妊娠; アポトーシス

Little is known regarding the immunological abnormalities in pre-ictal SLE. In our study, the positive rate of antinuclear antibodies (ANA) is significantly higher in children born to patients with SLE (SLE children: 27.8%; 67 of 241) compared with controls (7.4%; 4 of 54). Recently, it is reported that the risk for siblings of SLE patients to develop disease is estimated to be 20 times higher than that of general population. Based on the speculation that SLE children may be prone to develop SLE in future, a follow-up study was started to analyze the course of the immmunoregulatory change in SLE children.We investigated SLE children who were invited the outpatients clinic of the Juntendo hospital in the period from 1991 to 1999. 67 of 241 SLE children had detectable ANA. During the follow up, ANA changed to the positive in 9 cases aged from 4 to 8. In this reason, we analyzed CD4/CD8, CD3/CD19 (T cell/B cell) ratios and CD25, HLA-DR, CD80/CD86, Fas expression on the peripheral blood mo … More nonuclear cells (PBMC) in SLE children and controls aged from 1 to 10 by flow cytometry. 1) The CD4/CD8 ratios of SLE children transiently decreased in age 3-4. 2) Among SLE children, The CD4/CD8 ratios of ANA positive (14 cases) are significantly lower than that of ANA negative (58 cases). 3) There are significant differences of HLA-DR expression on CD3 positive cells between each age of SLE children. 4) Fas, CD80 and CD86 expression on CD3 positive cells of SLE children are significantly lower than that of controls. In SLE model mouse. Fas expression on CD5 positive B cells was biphsic with low (FasィイD1lowィエD1) and high(FasィイD1highィエD1). FasィイD1lowィエD1 population was relatively resistant to Fas mediated apoptosis and presumably autoantibody-secreting cells. To examined FasィイD1lowィエD1 population in 11 SLE children (ANA positive: 2, negative: 9), CD5 positive B cells on PBMC were stimulated with anti-CD40 mAb for 4 days and examined by now cytometry. Only 1 out or 11 had shown biphasic pattern, who had detectable ANA. The phenotypic change on immunoregulatory cells was occurred before and after production of ANA. During follow up, nobody was dignosed define SLE. This suggests that there are many steps of immunological changes to develop SLE. Further study remains to be necessary. Less

关于SLE发作前的免疫学异常知之甚少。在我们的研究中，抗核抗体（ANA）的阳性率显着高于儿童SLE患者（SLE儿童：27.8%; 67 241）与对照组（7.4%; 4 54）。最近有报道称，SLE患者的兄弟姐妹患病的风险估计比一般人群高20倍。基于SLE儿童可能是未来SLE的易感人群这一推测，我们对1991 ~ 1999年在顺天堂医院门诊就诊的SLE儿童进行了随访研究，以分析SLE儿童免疫调节变化的过程。241例SLE患儿中67例检出ANA。随访中ANA转阴9例，年龄4 ~ 8岁。为此，我们分析了CD 4/CD 8、CD 3/CD 19（T细胞/B细胞）比值和CD 25、HLA-DR、CD 80/CD 86、Fas表达在外周血单个核细胞（PBMC）中的变化，并与正常对照组比较，发现CD 25、HLA-DR、CD 80/CD 86、Fas表达在PBMC中的变化。 ...更多信息 流式细胞术检测1 ~ 10岁SLE患儿和对照组PBMC中单核细胞（PBMC）的变化。1)SLE患儿CD_4/CD_8比值在3 ~ 4岁呈一过性下降。2)在SLE患儿中，ANA阳性者（14例）的CD_4/CD_8比值明显低于ANA阴性者（58例）。3)SLE患儿CD 3阳性细胞表面HLA-DR的表达在各年龄组间差异有统计学意义。4)SLE患儿CD 3阳性细胞表面Fas、CD 80、CD 86的表达均明显低于对照组。SLE模型小鼠。CD 5阳性B细胞表面Fas表达呈双相性，即低表达（Fas受体D1低表达）和高表达（Fas受体D1高表达）。Fas介导的凋亡和自身抗体分泌细胞对Fas介导的凋亡和自身抗体分泌细胞相对抵抗。为检测11例SLE患儿（ANA阳性2例，ANA阴性9例）的Fas介导的D1亚群，用抗CD 40单克隆抗体刺激PBMC上CD 5阳性B细胞4天，流式细胞术检测其Fas介导的D1亚群。11例ANA阳性者中仅1例呈双相型。抗核抗体产生前后免疫调节细胞表型发生变化。随访中无一例确诊SLE。这表明，有许多步骤的免疫学变化发展成系统性红斑狼疮。仍需进一步研究。少

项目成果

橋本博史: "全身性エリテマトーデス患者の妊娠例における児の予後"平成8年度東京都特殊疾病(難病)に関する研究報告書. 68-71 (1997)

Hiroshi Hashimoto：“系统性红斑狼疮患者妊娠期婴儿的预后”1996年东京特殊疾病研究报告（难治性疾病）68-71（1997年）。

村島温子: "SLE患者より出生した児の長期予後"リウマチ科22. (印刷中)22.

Atsuko Murashima：“SLE 患者所生婴儿的长期预后”风湿病科 22。（出版中）22。

橋本博史: "全身性エリテマトーデス患者より出生した児の免疫学的異常"平成9年度東京都特殊疾病(難病)に関する研究報告書. 55-58 (1998)

Hiroshi Hashimoto：“系统性红斑狼疮患者所生婴儿的免疫异常”1997年东京特殊疾病研究报告（难治性疾病）55-58（1998）。

村山温子: "膠原病と妊娠"組織培養工学24. 24. 397-399 (1998)

Atsuko Murayama：《胶原病与妊娠》组织培养工程 24. 24. 397-399 (1998)

村島温子: "膠原病と妊娠"組織培養工学24. 24. 397-399 (1998)

村岛敦子：《胶原病与妊娠》组织培养工程 24. 24. 397-399 (1998)