Frank M B, McArthur R, Harley J B, Fujisaku A
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
J Clin Invest. 1990 Jan;85(1):33-9. doi: 10.1172/JCI114430.
Several of the heterogeneous clinical manifestations of systemic lupus erythematosus have been associated with specific autoantibodies. Associations between HLA class II antigens and autoantibodies to the ribonucleoproteins Ro(SSA) and La(SSB) have been reported in these patients. Because HLA class II molecules present antigen to T cell receptors (TCRs), we have searched for a TCR gene associated with the production of anti-Ro(SSA) antibodies. A pair of restriction fragment length polymorphisms (RFLPs), one of which hybridizes to the TCR constant region C beta 1 and the other to the C beta 2 gene, has been identified, suggesting these may be genotypic markers for an extended region of the TCR beta locus. This RFLP pair occurs in 76% of patients with Ro(SSA) precipitins, 84% of anti-Ro(SSA)-positive patients lacking La(SSB) precipitins, but only 41% of the patients lacking both precipitins (P = 0.0004). This disproportionate occurrence in a subset of lupus patients indicates that these RFLPs are not disease susceptibility markers, but rather are important markers for TCR genes whose products are involved in the production of anti-Ro(SSA) antibodies. The majority of patients who have these RFLPs and HLA class II antigens previously associated with the anti-Ro(SSA) response make this antibody, suggesting that interactions between products of these loci occur in response to Ro(SSA).
系统性红斑狼疮的几种异质性临床表现与特定自身抗体有关。在这些患者中，已报道了人类白细胞抗原（HLA）II类抗原与核糖核蛋白Ro（SSA）和La（SSB）自身抗体之间的关联。由于HLA II类分子将抗原呈递给T细胞受体（TCR），我们一直在寻找与抗Ro（SSA）抗体产生相关的TCR基因。已鉴定出一对限制性片段长度多态性（RFLP），其中一个与TCR恒定区Cβ1杂交，另一个与Cβ2基因杂交，这表明它们可能是TCRβ基因座扩展区域的基因型标记。这对RFLP在76%有Ro（SSA）沉淀素的患者、84%缺乏La（SSB）沉淀素的抗Ro（SSA）阳性患者中出现，但在两种沉淀素均缺乏的患者中仅占41%（P = 0.0004）。在一部分狼疮患者中的这种不成比例的出现表明，这些RFLP不是疾病易感性标记，而是TCR基因的重要标记，其产物参与抗Ro（SSA）抗体的产生。大多数具有这些RFLP以及先前与抗Ro（SSA）反应相关的HLA II类抗原的患者会产生这种抗体，这表明这些基因座的产物之间的相互作用是针对Ro（SSA）发生的。
