Satoh M, Kuwana M, Ogasawara T, Ajmani A K, Langdon J J, Kimpel D, Wang J, Reeves W H
Department of Medicine, Thurston Arthritis Research Center, University of North Carolina, Chapel Hill 27599.
J Immunol. 1994 Dec 15;153(12):5838-48.
Autoantibodies to RNA polymerases (RNAP) I and III are highly specific for scleroderma (SSc), whereas autoantibodies to RNAP II are associated with systemic lupus erythematosus (SLE) and overlap syndromes, as well as SSc. The specificities of autoantibodies to RNAP I, II, and III in 129 SSc sera were investigated in the present study. Immunoprecipitation and pulse-chase analysis demonstrated several patterns of autoantibody recognition of RNAPs. Some sera immunoprecipitated RNAP II only after its largest subunit was phosphorylated, suggesting that they contained autoantibodies that recognized an epitope carrying a phosphoamino acid. Autoantibody recognition of all three classes of RNAPs was influenced strongly by race. Although in SLE, autoantibodies to the phosphorylated form of RNAP II (RNAP IIO) were identified in all races, in SSc, these autoantibodies were seen in 21% of Japanese and 5% of Black patients, but never in Caucasians. A striking association of anti-RNAP IIO with anti-topoisomerase I (topo I) autoantibodies was found in Japanese and Black SSc, but not SLE, patients. However, anti-topo I Abs were not associated with anti-RNAP IIO in Caucasians. Japanese SSc patients who were positive for both anti-RNAP IIO and anti-topo I Abs had a significantly higher frequency of diffuse disease, pigmentation changes, flexion contractures, and acro-osteolysis than patients having autoantibodies to topo I alone, and were diagnosed at a younger age (p < 0.05). These data suggest that genetic factors (possibly HLA-linked) influence autoantibody specificity, and that different autoantibody fine specificities may either cause, or be predictive of, different clinical outcomes.
针对RNA聚合酶（RNAP）I和III的自身抗体对硬皮病（SSc）具有高度特异性，而针对RNAP II的自身抗体与系统性红斑狼疮（SLE）、重叠综合征以及SSc相关。本研究调查了129份SSc血清中针对RNAP I、II和III的自身抗体的特异性。免疫沉淀和脉冲追踪分析显示了自身抗体对RNAP的几种识别模式。一些血清仅在RNAP II的最大亚基磷酸化后才对其进行免疫沉淀，这表明它们含有识别携带磷酸氨基酸表位的自身抗体。所有三类RNAP的自身抗体识别都受到种族的强烈影响。虽然在SLE中，所有种族都发现了针对磷酸化形式的RNAP II（RNAP IIO）的自身抗体，但在SSc中，这些自身抗体在21%的日本患者和5%的黑人患者中出现，而在白种人中从未出现。在日本和黑人SSc患者中发现抗RNAP IIO与抗拓扑异构酶I（topo I）自身抗体有显著关联，但在SLE患者中未发现。然而，在白种人中抗topo I抗体与抗RNAP IIO无关。同时具有抗RNAP IIO和抗topo I抗体阳性的日本SSc患者，与仅具有抗topo I自身抗体的患者相比，弥漫性疾病、色素沉着改变、屈曲挛缩和肢端骨质溶解的发生率显著更高，且诊断年龄更小（p < 0.05）。这些数据表明遗传因素（可能与HLA相关）影响自身抗体特异性，并且不同的自身抗体精细特异性可能导致或预测不同的临床结果。
