Matsuki K, Juji T, Tokunaga K, Takamizawa M, Maeda H, Soda M, Nomura Y, Segawa M
Blood Transfusion Service, Tokyo University Hospital, Hongo, Japan.
J Clin Invest. 1990 Aug;86(2):392-9. doi: 10.1172/JCI114724.
HLA antigens in 104 Japanese patients and 41 families with myasthenia gravis (MG) were investigated. The frequencies of DR9 and DRw13 were significantly increased in the patients who developed MG before 3 yr of age. The DQw3 antigen was positive for all the patients that developed MG before 15 yr with only one exception. All the examined cases that developed MG before 3 yr (including this DQw3 negative patient) had the same DQA and DQB DNA restriction fragments. These HLA frequencies decreased as the age of onset increased, and no significant association was observed in adult-onset MG. No patients had B8, DR3, and DQw2. The relative risk was higher for the DR9/DRw13 heterozygotes (37.4) than for DR9 (16.4) or DRw13 (7.1) in the childhood-onset MG. Statistical analysis suggested that DR9 and DRw13 (or DQw1 and DQw3) act synergistically in the disease development. Family study revealed diverse DR9 haplotypes. The most frequent DRw13 haplotype was Bw44-BFF-C4A3B1-DRw13-DQw1, which may be evolutionarily related to the caucasian B8-DR3-DQw2 haplotype. These results showed that MG in early childhood in Japanese individuals is genetically different from that in adulthood and that in caucasians.
对104例日本重症肌无力（MG）患者及41个MG家系的HLA抗原进行了研究。3岁前发病的患者中，DR9和DRw13的频率显著增加。15岁前发病的所有患者中，除1例例外，DQw3抗原均为阳性。所有3岁前发病的受检病例（包括这位DQw3阴性患者）具有相同的DQA和DQB DNA限制性片段。这些HLA频率随发病年龄增加而降低，在成人发病的MG中未观察到显著关联。没有患者具有B8、DR3和DQw2。在儿童期发病的MG中，DR9/DRw13杂合子的相对风险（37.4）高于DR9（16.4）或DRw13（7.1）。统计分析表明，DR9和DRw13（或DQw1和DQw3）在疾病发生过程中协同作用。家系研究揭示了多样的DR9单倍型。最常见的DRw13单倍型是Bw44 - BFF - C4A3B1 - DRw13 - DQw1，其可能在进化上与白种人的B8 - DR3 - DQw2单倍型相关。这些结果表明，日本个体儿童期的MG在遗传上与成人期以及白种人的MG不同。
