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

• Published in: Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2019-08, Vol.71 (8), p.1360-1370
• Main Authors: Aussy, Audrey, Fréret, Manuel, Gallay, Laure, Bessis, Didier, Vincent, Thierry, Jullien, Denis, Drouot, Laurent, Jouen, Fabienne, Joly, Pascal, Marie, Isabelle, Meyer, Alain, Sibilia, Jean, Bader‐Meunier, Brigitte, Hachulla, Eric, Hamidou, Mohammed, Huë, Sophie, Charuel, Jean‐Luc, Fabien, Nicole, Viailly, Pierre‐Julien, Allenbach, Yves, Benveniste, Olivier, Cordel, Nadège, Boyer, Olivier
• Format: Article
• Language: English
• Subjects: Age; Aged; Antibodies; Autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; Biomarkers; Biomarkers, Tumor - blood; Biomarkers, Tumor - immunology; Cancer; Creatine; Creatine kinase; Dermatomyositis; Dermatomyositis - blood; Dermatomyositis - immunology; Dermatomyositis - mortality; Female; Fluorescence; Hazards; Health risks; Humans; Immunoassay; Immunoglobulin G; Immunoglobulin G - immunology; Kinases; Life Sciences; Male; Malignancy; Men; Middle Aged; Mortality; Multivariate Analysis; Neoplasms - blood; Neoplasms - immunology; Proportional Hazards Models; Regression analysis; Regression models; Retrospective Studies; Risk analysis; Risk Assessment; Risk Factors; Sex; Survival; Transcription Factors - immunology
• ISSN: 2326-5191; 2326-5205; 2326-5205; 2326-5191
• DOI: 10.1002/art.40895

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.