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

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.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / immunology
  • Dermatomyositis / blood*
  • Dermatomyositis / immunology
  • Dermatomyositis / mortality*
  • Female
  • Humans
  • Immunoglobulin G / immunology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasms / blood*
  • Neoplasms / immunology
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Transcription Factors / immunology*

Substances

  • Autoantibodies
  • Biomarkers, Tumor
  • Immunoglobulin G
  • TRIM33 protein, human
  • Transcription Factors