Major histocompatibility genes and ankylosing spondylitis
Major histocompatibility genes and ankylosing spondylitis
复制标题
DOI：
10.1016/j.berh.2006.03.004
复制
发表时间：
2006-06-01
影响因子：
5.2
通讯作者：
Reveille, John D.
中科院分区：
文献类型：
--
作者：
Reveille, John D.
HLA-B27与强直性脊柱炎的关联占总疾病风险的近40%。然而，一般人群中只有不到5%的B27阳性个体受到影响。全基因组扫描表明，其他主要组织相容性复合体基因进一步增加了这种风险，尽管与HLA-B27的连锁不平衡混淆了它们的精确鉴定。迄今为止，已鉴定出超过31种HLA-B27变体，它们是从原始的B27等位基因（B*2705）沿沿着三条地理线进化而来的。白种人脊柱炎患者的HLA-B*2705和B*2702是主要亚型，亚洲人脊柱炎患者的HLA-B *2704和B*2707是主要亚型。HLA-B*2706和B*2709与疾病无关，关于HLA-27如何引起脊柱关节炎有四种理论：（1）HLA-B27是一种细菌源性的“致关节炎肽”（2）HLA-B27重链的错误折叠或同源二聚化导致促炎反应;（3）HLA-B27阳性个体对致关节炎生物的细胞内杀伤能力不足;（4）HLA-B27本身由于与细菌蛋白的序列同源性而成为自身抗原。
The association of HLA-B27 with ankylosing spondylitis accounts for nearly 40% of the total disease risk. However, fewer than 5% of B27-positive individuals in the general population become affected. Genomewide scans suggest that other major histocompatibility complex genes further heighten this risk, although linkage disequilibrium with HLA-B27 has confounded their precise identification.Over 31 variants of HLA-B27 have been identified to date, which have evolved from the original B27 allele (B*2705) along three geographic lines. HLA-B*2705 and B*2702 are the primary subtypes in Caucasians with spondylitis, and B*2704 and B*2707 are the primary subtypes in Asians. HLA-B*2706 and B*2709 are not disease associated.There are four theories of how HLA-27 causes spondyloarthritis: (1) HLA-B27 presents a bacterially derived 'arthritogenic peptide' (not yet identified); (2) misfolding or homodimerization of HLA-B27 heavy chains results in a pro-inflammatory response; (3) HLA-B27-positive individuals have deficient intracellular killing of arthritogenic organisms; and (4) HLA-B27 itself, due to sequence homology with bacterial proteins, becomes autoantigenic.