Audrey Aussy1, Manuel Fréret1, Laure Gallay2, Didier Bessis3, Thierry Vincent4, Denis Jullien5, Laurent Drouot1, Fabienne Jouen1, Pascal Joly1, Isabelle Marie1, Alain Meyer6, Jean Sibilia6, Brigitte Bader-Meunier7, Eric Hachulla8, Mohammed Hamidou9, Sophie Huë10, Jean-Luc Charuel11, Nicole Fabien2, Pierre-Julien Viailly12, Yves Allenbach13, Olivier Benveniste13, Nadège Cordel14, Olivier Boyer1. 1. Normandy University, University of Rouen, INSERM U1234, Rouen University Hospital, Rouen, France. 2. Édouard Herriot University Hospital, Lyon, France. 3. St. Eloi Hospital and Montpellier University Hospital, INSERM U1051, Montpellier, France. 4. St. Eloi Hospital and Montpellier University Hospital, Montpellier, France. 5. Lyon University and Édouard Herriot University Hospital, Lyon, France. 6. Strasbourg University Hospital and Centre de Référence des Maladies Autoimmunes Rares, Strasbourg, France. 7. Necker University Hospital, AP-HP, Paris, France. 8. European Reference Network on Connective Tissue and Musculoskeletal Diseases, University of Lille, Hospital Claude Huriez, Lille, France. 9. Hôtel-Dieu and CHU de Nantes, Nantes, France. 10. AP-HP, Henri Mondor Hospital, Créteil, France. 11. AP-HP, Pitié-Salpêtrière University Hospital, Paris, France. 12. Normandy University, University of Rouen, INSERM U1245, Rouen, France. 13. AP-HP, Pitié-Salpêtrière University Hospital, Centre de Référence Maladies Neuro-Musculaires, DHU i2B, INSERM UMRS 974, Paris, France. 14. Normandy University, University of Rouen, INSERM U1234, Rouen University Hospital, Rouen, France, and French West Indies University and Pointe-à-Pitre University Hospital, Pointe-à-Pitre, Guadeloupe, France.
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.
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 DMpatients 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 DMpatients 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 DMpatients.
Authors: Alexander G S Oldroyd; Andrew B Allard; Jeffrey P Callen; Hector Chinoy; Lorinda Chung; David Fiorentino; Michael D George; Patrick Gordon; Kate Kolstad; Drew J B Kurtzman; Pedro M Machado; Neil J McHugh; Anna Postolova; Albert Selva-O'Callaghan; Jens Schmidt; Sarah Tansley; Ruth Ann Vleugels; Victoria P Werth; Rohit Aggarwal Journal: Rheumatology (Oxford) Date: 2021-06-18 Impact factor: 7.580