Satoh M, Ajmani A K, Ogasawara T, Langdon J J, Hirakata M, Wang J, Reeves W H
Department of Medicine, Thurston Arthritis Research Center, University of North Carolina, Chapel Hill 27599-7280.
J Clin Invest. 1994 Nov;94(5):1981-9. doi: 10.1172/JCI117550.
Autoantibodies to RNA polymerases (RNAP) I, II, and III are reported to be highly specific for the diagnosis of scleroderma (systemic sclerosis, SSc). In the present study, the specificity of autoantibodies to RNAP I and III for SSc was confirmed by immunoprecipitation of 35S-labeled proteins. However, we report here the previously unrecognized production of anti-RNAP II autoantibodies by 9-14% of patients with SLE and mixed connective tissue disease/overlap syndrome. 12 out of 32 anti-RNAP II positive sera (group 1) immunoprecipitated a diffuse 220-240-kD band identified as the largest subunit of RNAP II whereas the remaining 20 (group 2) immunoprecipitated preferentially the 240-kD phosphorylated (IIo) form of the large subunit. After pulse labeling, group 1 sera immunoprecipitated only the 220-kD (IIa) RNAP II subunit, whereas the diffuse IIa/IIo band plus the 145-kD second largest RNAP II subunit (IIc) were immunoprecipitated after several hours of cold chase, suggesting that these sera recognized primarily the largest subunit of RNAP II. Group 2 sera recognized the IIc subunit after pulse labeling, and immunoprecipitated the IIc and IIo, but not the IIa, subunits after cold chase. Although it has been suggested that autoantibodies to RNAP II are usually accompanied by anti-RNAP I/III in SSc, all but one of the anti-RNAP II positive sera from SLE or mixed connective tissue disease/overlap syndrome patients, as well as most of the SSc sera, were negative for anti-RNAP I/III. Moreover, in contrast to previous reports suggesting that anti-RNAP antibodies rarely coexist with other SSc subset marker antibodies, anti-RNAP II antibodies were often accompanied by anti-Ku, anti-nRNP, or anti-topoisomerase I autoantibodies in the present study. We conclude that autoantibodies to RNAP II are not a specific marker for SSc, whereas autoantibodies to RNAP I/III are associated primarily with SSc. In addition, we have identified two distinctive patterns of RNAP II antigen recognition by autoantibodies, one of them characterized by specific recognition of the transcriptionally active (phosphorylated) form of RNAP II. The clinical significance of these different patterns remains to be determined.
据报道，针对RNA聚合酶（RNAP）I、II和III的自身抗体对硬皮病（系统性硬化症，SSc）的诊断具有高度特异性。在本研究中，通过对35S标记蛋白进行免疫沉淀，证实了针对RNAP I和III的自身抗体对SSc的特异性。然而，我们在此报告，9%至14%的系统性红斑狼疮（SLE）患者和混合性结缔组织病/重叠综合征患者会产生此前未被认识到的抗RNAP II自身抗体。32份抗RNAP II阳性血清中的12份（第1组）免疫沉淀出一条弥散的220 - 240 kDa条带，该条带被鉴定为RNAP II的最大亚基，而其余20份（第2组）则优先免疫沉淀出大亚基的240 kDa磷酸化（IIo）形式。脉冲标记后，第1组血清仅免疫沉淀出220 kDa（IIa）的RNAP II亚基，而在冷追赶数小时后，弥散的IIa/IIo条带以及145 kDa的第二大RNAP II亚基（IIc）被免疫沉淀，这表明这些血清主要识别RNAP II的最大亚基。第2组血清在脉冲标记后识别IIc亚基，冷追赶后免疫沉淀出IIc和IIo亚基，但不沉淀IIa亚基。尽管有人提出，在SSc中，抗RNAP II自身抗体通常伴有抗RNAP I/III，但来自SLE或混合性结缔组织病/重叠综合征患者的抗RNAP II阳性血清中，除一份外，其余所有血清以及大多数SSc血清的抗RNAP I/III均为阴性。此外，与之前的报道相反，之前的报道表明抗RNAP抗体很少与其他SSc亚组标记抗体共存，而在本研究中，抗RNAP II抗体常伴有抗Ku、抗nRNP或抗拓扑异构酶I自身抗体。我们得出结论，抗RNAP II自身抗体不是SSc的特异性标志物，而抗RNAP I/III自身抗体主要与SSc相关。此外，我们已经确定了自身抗体识别RNAP II抗原的两种不同模式，其中一种模式的特征是特异性识别转录活性（磷酸化）形式的RNAP II。这些不同模式的临床意义仍有待确定。
