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抗转录中介因子 1γ 自身抗体 IgG2 同型是成人皮肌炎癌症和死亡的生物标志物。

The IgG2 Isotype of Anti-Transcription Intermediary Factor 1γ Autoantibodies Is a Biomarker of Cancer and Mortality in Adult Dermatomyositis.

机构信息

Normandy University, University of Rouen, INSERM U1234, Rouen University Hospital, Rouen, France.

Édouard Herriot University Hospital, Lyon, France.

出版信息

Arthritis Rheumatol. 2019 Aug;71(8):1360-1370. doi: 10.1002/art.40895. Epub 2019 Jul 8.

Abstract

OBJECTIVE

Anti-transcription intermediary factor 1γ (anti-TIF1γ) antibodies are the main predictors of cancer in dermatomyositis (DM). Yet, a substantial proportion of anti-TIF1γ-positive DM patients do not develop cancer. This study was undertaken to identify biomarkers to better evaluate the risk of cancer and mortality in DM.

METHODS

This multicenter study was conducted in adult anti-TIF1γ-positive DM patients from August 2013 to August 2017. Anti-TIF1γ autoantibody levels and IgG subclasses were identified using a newly developed quantitative immunoassay. Age, sex, DM signs and activity, malignancy, and creatine kinase (CK) level were recorded. Risk factors were determined by univariate and multivariate analysis according to a Cox proportional hazards regression model.

RESULTS

Among the 51 adult patients enrolled (mean ± SD age 61 ± 17 years; ratio of men to women 0.65), 40 (78%) had cancer and 21 (41%) died, with a mean ± SD survival time of 10 ± 6 months. Detection of anti-TIF1γ IgG2 was significantly associated with mortality (P = 0.0011) and occurrence of cancer during follow-up (P < 0.0001), with a 100% positive predictive value for cancer when the mean fluorescence intensity of anti-TIF1γ IgG2 was >385. None of the patients developed cancer after 24 months of follow-up. Univariate survival analyses showed that mortality was also associated with age >60 years (P = 0.0003), active DM (P = 0.0042), cancer (P = 0.0031), male sex (P = 0.011), and CK level >1,084 units/liter (P = 0.005). Multivariate analysis revealed that age >60 years (P = 0.015) and the presence of anti-TIF1γ IgG2 (P = 0.048) were independently associated with mortality.

CONCLUSION

Our findings indicate that anti-TIF1γ IgG2 is a potential new biomarker of cancer that should be helpful in identifying the risk of mortality in anti-TIF1γ-positive DM patients.

摘要

目的

抗转录中介因子 1γ(anti-TIF1γ)抗体是皮肌炎(DM)发生癌症的主要预测因子。然而,相当一部分抗 TIF1γ 阳性 DM 患者并未发展为癌症。本研究旨在寻找生物标志物,以更好地评估 DM 患者的癌症风险和死亡率。

方法

本多中心研究纳入了 2013 年 8 月至 2017 年 8 月期间抗 TIF1γ 阳性的成年 DM 患者。使用新开发的定量免疫分析法检测抗 TIF1γ 自身抗体水平和 IgG 亚类。记录年龄、性别、DM 症状和活动、恶性肿瘤和肌酸激酶(CK)水平。根据 Cox 比例风险回归模型,通过单变量和多变量分析确定危险因素。

结果

本研究共纳入 51 例成年患者(平均年龄 61 ± 17 岁;男女比例 0.65),其中 40 例(78%)患有癌症,21 例(41%)死亡,平均生存时间为 10 ± 6 个月。抗 TIF1γ IgG2 的检测与死亡率(P = 0.0011)和随访期间癌症的发生显著相关(P < 0.0001),当抗 TIF1γ IgG2 的平均荧光强度>385 时,癌症的阳性预测值为 100%。没有患者在随访 24 个月后发生癌症。单变量生存分析显示,死亡率还与年龄>60 岁(P = 0.0003)、活动性 DM(P = 0.0042)、癌症(P = 0.0031)、男性(P = 0.011)和 CK 水平>1084 单位/升(P = 0.005)相关。多变量分析显示,年龄>60 岁(P = 0.015)和抗 TIF1γ IgG2 的存在(P = 0.048)与死亡率独立相关。

结论

我们的研究结果表明,抗 TIF1γ IgG2 是癌症的一种潜在新生物标志物,有助于识别抗 TIF1γ 阳性 DM 患者的死亡风险。

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