Reveille John D
Division of Rheumatology, The University of Texas Health Science Center at Houston, 6431, Fannin, TX 77030 , USA.
Best Pract Res Clin Rheumatol. 2006 Jun;20(3):601-9. doi: 10.1016/j.berh.2006.03.004.
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 (B2705) along three geographic lines. HLA-B2705 and B2702 are the primary subtypes in Caucasians with spondylitis, and B2704 and B2707 are the primary subtypes in Asians. HLA-B2706 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.
HLA - B27与强直性脊柱炎的关联占疾病总风险的近40%。然而，普通人群中B27阳性个体患该病的比例不到5%。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识别。迄今为止，已鉴定出超过31种HLA - B27变体，它们沿着三条地理线路从原始的B27等位基因（B2705）进化而来。HLA - B2705和B2702是白种人脊柱炎患者的主要亚型，B2704和B2707是亚洲人的主要亚型。HLA - B2706和B*2709与疾病无关。关于HLA - 27如何导致脊柱关节炎有四种理论：（1）HLA - B27呈递一种细菌衍生的“致关节炎肽”（尚未确定）；（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体的细胞内杀伤能力不足；（4）由于与细菌蛋白的序列同源性，HLA - B27本身成为自身抗原。
