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ANALYSIS OF THE PATHOGENESIS OF THE SERONEGATIVE AUTOIMUNE DISEASE

血清阴性自身免疫病发病机制分析

基本信息

批准号：
13670846
负责人：
SHINOMIYA Noriaki
金额：
$ 1.92万
依托单位：
TOHO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670846/
关键词：
childhood-onset myasthenia gravis ant-acetylcholine receptor autoantibody seronegative autoimrnmue HLA DR DO allele latent general type DRB1^*1302 DOA1^*0102 DOB1^*0604 HLA-DR DQタイプ潜在性全身型 TCRVαVβレパートリー重症筋無力症 DQA1^*0302 DQB1

项目摘要

As most patients with myasthenia gravis(MG)of childhood onset have low or negative ant-acetylcholine receptor(AChR) autoantibody titier, the role of anti-AChR autoantibodies as the cause of muscle weakness remains as open question.As for the prevalence of child-hood MG in Japan, the largest onset-age group was found to be under three years.To elucidate whether the Japanese patients with childhood-onset MG is a variant type, the correlation between clinical features and HLA DR/DQ allele frequencies was examined in 87 Japanese patients with childhood-onset disease.HLA genotypes DRB1^*1302/DQA1^*0102/DQB1^*0604 and DRB1^*1302/DQA1^*0102/DQB1^*0604 were signiticant higher in patients than in healthy controls(Pc<0.0001, RR=8.5 ; Pc<0.0001, RR=5.5, for two genotypes, respectively).Patients who had a significant higher likelihood of the HLA types DRB1^*1302/DQA1^*0102/DQB1^*0604 or DRB1^*1302/DQA1^*0102/DQB1^*0604 belonged to the latent general type(LG) of MG ; this is clinically ocular type, but shows myasthenic electromyographic findings in extremity muscles.The LG type of MG was observed in 78% of patients exhibiting the clinically ocular type ; this group comprised approximately 75% of patients with childhood-onset MG.These data suggested that the LG type with childhood-onset associated with HLA types DRB1^*1302/DQA1^*0102/DQB1^*0604 is a specific clinical type of childhood-onset MG which may carry a specific genes predisposing toward the disease.

由于大多数儿童期发病的重症肌无力（MG）患者抗乙酰胆碱受体（AChR）自身抗体滴度低或阴性，抗AChR自身抗体在肌无力中的作用仍是一个悬而未决的问题。至于日本儿童MG的患病率，发现最大的发病年龄群体是三岁以下。为了阐明日本儿童期发病的MG患者是否是一种变异型，我们对87例日本儿童期发病患者的临床特征与HLA DR/DQ等位基因频率的相关性进行了研究。HLA基因型DRB1^*1302/DQA1^*0102/DQB1^*0604和DRB1^*1302/DQA1^*0102/DQB1^*0604在患者中显著高于健康对照组（Pc<0.0001， RR=8.5; Pc<0.0001， RR=5.5）。HLA类型DRB1^*1302/DQA1^*0102/DQB1^*0604或DRB1^*1302/DQA1^*0102/DQB1^*0604的可能性较高的患者属于MG的潜在一般型（LG）；临床上为眼型，但在四肢肌肉中表现为肌无力。临床上表现为眼型的MG患者中有78%为LG型；该组约占儿童期发病MG患者的75%。这些数据提示，与HLA型DRB1^*1302/DQA1^*0102/DQB1^*0604相关的儿童期发病的LG型是儿童期发病MG的一种特殊的临床类型，可能携带特定的易感基因。