Fiorentino David F, Chung Lorinda S, Christopher-Stine Lisa, Zaba Lisa, Li Shufeng, Mammen Andrew L, Rosen Antony, Casciola-Rosen Livia
Stanford University School of Medicine, Stanford, California.
Arthritis Rheum. 2013 Nov;65(11):2954-62. doi: 10.1002/art.38093.
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 (35) S-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.
由于皮肌炎（DM）与恶性肿瘤风险增加相关，准确识别可能患有癌症的患者很重要。最近有几个研究小组利用放射性标记细胞裂解物进行免疫沉淀，发现抗转录中介因子1γ（抗TIF-1γ）抗体与DM中的恶性肿瘤有关。我们开展这项研究，以开发灵敏、特异的检测方法来检测抗TIF-1γ抗体和核基质蛋白NXP-2，并评估它们与DM中恶性肿瘤的相关性。
为检测抗TIF-1γ抗体，使用过表达TIF-1γ的HeLa细胞裂解物进行免疫沉淀，通过免疫印迹法进行检测。抗NXP-2抗体通过使用体外转录/翻译产生的（35）S-甲硫氨酸标记的NXP-2进行免疫沉淀测定。我们分析了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队列患者血清。
分别有17%和38%的患者有抗NXP-2和抗TIF-1γ抗体。对NXP-2或TIF-1γ的反应性可识别出83%的与癌症相关的DM患者。除年龄较大和男性外，多变量分析显示癌症与抗NXP-2或抗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NXP-2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（在55%的患者中发现），并且存在于大多数与癌症相关的DM患者中。
