Genetic polymorphism of SLE

在SLE中，与广谱自身抗体相关的疾病特征多样性发展。存在患有抗磷脂综合征、自身免疫性溶血性贫血、自身免疫性血小板减少症和/或甚至B细胞慢性淋巴细胞白血病（B-CLL）的患者亚群。由于SLE是一种多基因疾病，个体患者的疾病特征的差异被认为是由于导致每种病理状况的疾病易感基因的不同组合。这一概念与在几种遗传决定的SLE易感小鼠模型中观察到的结果一致，其中在一种模型中检测到特定的自身抗体，但在其他模型中未检测到。研究表明，除了疾病易感性等位基因，疾病修饰因子也参与每种疾病特征的发展。为了描述潜在的遗传基础，我们分析了含有有助于每个SLE特征的基因座的染色体片段，使用NZB，NZW，（NZB x NZW）F1，（NZW x BXSB）F1，它们的回交后代，同源品系和转基因小鼠。结果表明，每个疾病特征是由两个到三个或更多个主要等位基因的不同组合独立控制的，其中一些是常见的，一些是独特的不同特征。基因相互作用，其中一些在协调的方式和一些，在添加剂的方式作为一个阈值的易感性模型的疾病易感性，建议。有几个潜在的重要的候选基因，这可能是相关的每一个疾病的特征。我们可以确定几个等位基因，调节异常增殖和/或分化的B1，细胞，前体的致病性自身抗体产生细胞和B-CLL。

In SLE,a diversity of disease features in association with a wide spectrum of autoantibodies develops. There are subsets of patients with either antiphospholipid syndrome, autoimmune hemolytic anemia, autoimmune thrombocytopenia and/or even B-cell chronic lymphocytic leukemia (B-CLL). Because SLE is a multigenic disease, diversities of disease features in individual patients are thought to be due to different combinations of disease susceptibility genes contributing to each pathologic condition. This notion is consistent with findings observed in several genetically determined SLE-prone mouse models, in which particular autoantibodies are detected in one, but not in others. Studies indicated that, in addition to disease susceptibility alleles, disease modifiers are also involved in the development of each disease feature. To delineate the underlying genetic basis, we analyzed chromosomal segments containing loci contributing to each SLE feature, using NZB,NZW,(NZB x NZW) F1, (NZW x BXSB) F1, their backcross progeny, congenic strains, and transgenic mice. Results showed that each disease feature was independently controlled by different combinations of two to three, or more, major alleles, in which some were common and some were unique for different features. Gene interactions, in which some functioned in a coordinate manner and some, in an additive manner as a threshold liability model for the disease susceptibility, were suggested. There were several potentially important candidate genes, which may be relevant to each disease feature. We could identify several alleles which regulate aberrant proliferation and/or differentiation of B1, cells, precursors of both pathogenic autoantibody-producing cells and B-CLL.