Roles of DRB1*1501 and DRB1*1502 in the pathogenesis of aplastic anemia
Roles of DRB1*1501 and DRB1*1502 in the pathogenesis of aplastic anemia
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DOI：
10.1016/j.exphem.2006.09.002
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发表时间：
2007-01-01
影响因子：
2.6
通讯作者：
Nakao, Shinji
中科院分区：
文献类型：
--
作者：
Sugimori, Chiharu;Yamazaki, Hirohito;Nakao, Shinji
Objective.尽管许多报告已经证明再生障碍性贫血（AA）中HLA-DR 15的发生率显着增加，但HLA-DR 15在AA免疫机制中的确切作用仍不清楚。我们在此阐明DRB 1 *1501和DRB 1 *1502（决定HLA-DR 15呈递的两个DRB 1等位基因）在AA的病理生理学中的差异。我们调查了140例日本AA患者 * HLA-DRB 1等位基因与少量CD 55（-）CD 59（-）（PNH型）血细胞的存在以及抗胸腺细胞球蛋白（ATG）加环孢菌素（CsA）治疗反应的关系。在30种不同的DRB 1等位基因中，只有DRB 1 *1501（33.6%对12.8%，p（c）< 0.01）和DRB 1 *1502（43.6%对24.4%，p（c）< 0.01）在AA患者中的频率显著高于对照组。AA患者HLA-DR 15基因携带者年龄偏大，尤其是40岁以上患者DRB 1 *1502基因频率（52.4%）明显高于40岁以下患者（16.2%，p（c）< 0.01）。只有DRB 1 *1501与PNH型细胞的小群体的存在显著相关，并且在单变量分析中也显示出对ATG加CsA治疗的良好反应。多因素分析显示，只有少量PNH型细胞的存在是免疫抑制治疗效果良好的重要因素（P < 0.01）。虽然DRB 1 *1501和DRB 1 *1502都有助于AA的发生，但两个等位基因的贡献方法不同。(c)2007年国际实验血液学学会。爱思唯尔公司出版。
Objective. Although a number of reports have documented a significantly increased incidence of HLA-DR15 in aplastic anemia (AA), the exact role of HLA-DR15 in the immune mechanisms of AA remains unclear. We herein clarify the difference between DRB1*1501 and DRB1*1502, the two DRB1 alleles that determine the presentation of HLA-DR15, in the pathophysiology of AA.Materials and Methods. We investigated the relationships of the patients* HLA-DRB1 allele with both the presence of a small population of CD55(-)CD59(-) (PNH-type) blood cells and the response to antithymocyte globulin (ATG) plus cyclosporin (CsA) therapy in 140 Japanese AA patients.Results. Of the 30 different DRB1 alleles, only DRB1*1501 (33.6% vs 12.8%, p(c) < 0.01) and DRB1*1502 (43.6% vs 24.4%, p(c) < 0.01) displayed significantly higher frequencies among the AA patients than among a control. AA patients possessing HLA-DR15 tended to be old, and especially, the frequency of DRB1*1502 in patients 40 years of age and older (52.4%) was markedly higher than that in those younger than 40 years old (16.2%, p(c) < 0.01). Only DRB1*1501 was significantly associated with the presence of a small population of PNH-type cells and it also showed a good response to ATG plus CsA therapy in a univariate analysis. A multivariate analysis showed only the presence of a small population of PNH-type cells to be a significant factor associated with a good response to the immunosuppressive therapy (P < 0.01).Conclusions. Although both DRB1*1501 and DRB1*1502 contribute to the development of AA, the methods of contribution differ between the two alleles. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc.