Fujisaku A, Frank M B, Neas B, Reichlin M, Harley J B
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
J Clin Invest. 1990 Aug;86(2):606-11. doi: 10.1172/JCI114751.
A strong gene interaction between HLA-DQ1 and DQ2 alleles has been associated with anti-Ro/SSA autoantibodies (Harley, J.B., M. Reichlin, F. C. Arnett, E. L. Alexander, W. B. Bias, and T. T. Provost. 1986. Science [Wash. DC]. 232:1145-1147; Harley, J. B., A. S. Sestak, L. G. Willis, S. M. Fu, J. A. Hansen, and M. Reichlin. 1989. Arthritis Rheum. 32:826-836; Hamilton, R. G., J. B. Harley, W. B. Bias, M. Roebber, M. Reichlin, M. C. Hochberg, and F. C. Arnett. 1988. Arthritis Rheum. 31:496-505). To test a gene complementation mechanism for these results, restriction fragment length polymorphisms (RFLP) of the DQ alpha and DQ beta genes have been related to Ro/SSA precipitins in patients with systemic lupus erythematosus. In this study Ro/SSA precipitins are related to the simultaneous presence of a particular pair of RFLPs. A DQ alpha RFLP associated with HLA-DQ1 and a DQ beta RFLP associated with HLA-DQ2 predict that the alpha beta heterodimer in HLA-DQ1/DQ2 heteroxygotes is most closely related to anti-Ro/SSA autoantibodies, thereby supporting a gene complementation mechanism. Beyond this effect, an RFLP associated with HLA-DQ2 and/or DR7 is also related to Ro/SSA precipitins. Multiple molecular histocompatibility mechanisms are implicated, therefore, in the production of anti-Ro/SSA autoantibodies in autoimmune disease. For anti-Ro/SSA autoantibodies in SLE, and perhaps more generally, these data show that the histocompatibility antigens are among the elements that confer autoimmune response specificity and restrict the production of particular autoantibodies among patients with systemic lupus erythematosus.
HLA - DQ1和DQ2等位基因之间存在强烈的基因相互作用,这与抗Ro/SSA自身抗体有关(Harley, J.B., M. Reichlin, F. C. Arnett, E. L. Alexander, W. B. Bias, and T. T. Provost. 1986. Science [Wash. DC]. 232:1145 - 1147; Harley, J. B., A. S. Sestak, L. G. Willis, S. M. Fu, J. A. Hansen, and M. Reichlin. 1989. Arthritis Rheum. 32:826 - 836; Hamilton, R. G., J. B. Harley, W. B. Bias, M. Roebber, M. Reichlin, M. C. Hochberg, and F. C. Arnett. 1988. Arthritis Rheum. 31:496 - 505)。为了验证这些结果的基因互补机制,已将DQα和DQβ基因的限制性片段长度多态性(RFLP)与系统性红斑狼疮患者的Ro/SSA沉淀素相关联。在本研究中,Ro/SSA沉淀素与特定一对RFLP的同时存在相关。与HLA - DQ1相关的DQα RFLP和与HLA - DQ2相关的DQβ RFLP表明,HLA - DQ1/DQ2杂合子中的αβ异二聚体与抗Ro/SSA自身抗体关系最为密切,从而支持了基因互补机制。除此之外,与HLA - DQ2和/或DR7相关的RFLP也与Ro/SSA沉淀素有关。因此,多种分子组织相容性机制参与了自身免疫性疾病中抗Ro/SSA自身抗体的产生。对于系统性红斑狼疮中的抗Ro/SSA自身抗体,或许更普遍地说,这些数据表明组织相容性抗原是赋予自身免疫反应特异性并限制系统性红斑狼疮患者中特定自身抗体产生的因素之一。