Most patients with cancer-associated dermatomyositis have antibodies to nuclear matrix protein NXP-2 or transcription intermediary factor 1γ.
Most patients with cancer-associated dermatomyositis have antibodies to nuclear matrix protein NXP-2 or transcription intermediary factor 1γ.
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DOI：
10.1002/art.38093
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发表时间：
2013-11
影响因子：
--
通讯作者：
Casciola-Rosen, Livia
中科院分区：
文献类型：
--
作者：
Fiorentino, David F.;Chung, Lorinda S.;Christopher-Stine, Lisa;Zaba, Lisa;Li, Shufeng;Mammen, Andrew L.;Rosen, Antony;Casciola-Rosen, Livia
由于皮肌炎（DM）与恶性肿瘤的风险增加有关，因此准确识别可能患有癌症的患者非常重要。使用放射性标记细胞裂解物的免疫沉淀，几个研究小组最近表明，抗转录中间因子1γ（抗TIF-1γ）抗体与DM中的恶性肿瘤相关。我们开展这项研究是为了开发灵敏、特异的检测方法来检测抗TIF-1γ和核基质蛋白NXP-2的抗体，并评估它们与DM恶性肿瘤的相关性。为了检测抗TIF-1γ抗体，使用由过表达TIF-1γ的HeLa细胞制备的裂解物进行免疫沉淀，并通过免疫印迹进行检测。使用通过体外转录/翻译产生的35 S-甲硫氨酸标记的NXP-2，通过免疫沉淀法测定抗NXP-2抗体。我们分析了来自斯坦福大学皮肤科诊所（n = 111）和约翰·霍普金斯肌炎中心（n = 102）的DM队列的患者血清。共有17%和38%的患者分别具有抗NXP-2和TIF-1γ的抗体。对NXP-2或TIF-1γ的反应性确定了83%的癌症相关DM患者。除年龄较大和男性外，在多变量分析中，癌症与恩智浦-2或TIF-1γ抗体相关（比值比3.78 [95%置信区间1.33-10.8]）。按性别分层显示，抗恩智浦-2抗体与男性癌症特异性相关（比值比5.78 [95%置信区间1.35-24.7]）。这些研究表明，抗NXP-2和抗TIF-1γ抗体是常见的DM特异性抗体（见于55%的患者），并且存在于大多数癌症相关DM患者中。
Since dermatomyositis (DM) is associated with an increased risk of malignancy, accurate identification of patients likely to harbor cancers is important. Using immunoprecipitations from radiolabeled cell lysates, several groups recently showed that anti–transcription intermediary factor 1γ (anti–TIF-1γ) antibodies are associated with malignancy in DM. We undertook this study to develop sensitive, specific assays to detect antibodies against TIF-1γ and nuclear matrix protein NXP-2 and to evaluate their association with malignancy in DM. To detect anti–TIF-1γ antibodies, immunoprecipitations were performed using lysates made from HeLa cells overexpressing TIF-1γ, with detection by immunoblotting. Anti–NXP-2 antibodies were assayed by immunoprecipitation using 35S-methionine–labeled NXP-2 generated by in vitro transcription/translation. We analyzed patient sera from DM cohorts seen at the Stanford University Dermatology Clinic (n = 111) and the Johns Hopkins Myositis Center (n = 102). A total of 17% and 38% of patients had antibodies against NXP-2 and TIF-1γ, respectively. Reactivity against either NXP-2 or TIF-1γ identified 83% of patients with cancer-associated DM. In addition to older age and male sex, cancer was associated with antibodies to NXP-2 or TIF-1γ on multivariate analysis (odds ratio 3.78 [95% confidence interval 1.33–10.8]). Stratification by sex revealed that anti–NXP-2 was specifically associated with cancer in males (odds ratio 5.78 [95% confidence interval 1.35–24.7]). These studies demonstrate that anti–NXP-2 and anti–TIF-1γ antibodies are frequent DM specificities (found in 55% of patients) and are present in most patients with cancer-associated DM.
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