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

Audrey Aussy (1) , Manuel Fréret (2) , Laure Gallay (3, 4) , Didier Bessis (5, 6) , Thierry Vincent (6, 5) , Denis Jullien (4) , Laurent Drouot (2, 1) , Fabienne Jouen (1) , Pascal Joly (1) , Isabelle Marie (7) , Alain Meyer (8) , Jean Sibilia (9, 8) , Brigitte Bader‐meunier , Eric Hachulla (10, 11) , Mohammed Hamidou , Sophie Hue (12) , Jean‐luc Charuel , Nicole Fabien (13) , Pierre‐julien Viailly (14) , Yves Allenbach (15) , Olivier Benveniste (16) , Nadège Cordel (17) , Olivier Boyer (1)

1 PANTHER - Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices
2 Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes
3 LBMC UMR 5239 - Laboratoire de biologie et modélisation de la cellule
4 Hôpital Edouard Herriot [CHU - HCL]
5 INM - Institut des Neurosciences de Montpellier
6 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
7 Service de Médecine Interne [CHU Rouen]
8 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
9 Physiopathologie des arthrites
10 Service de médecine interne
11 LIRIC - Lille Inflammation Research International Center - U 995
12 IMRB - Institut Mondor de Recherche Biomédicale
13 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
14 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
15 DEPARTAMENT DE QUíMICA ORGàNICA - Facultat de Química
16 SU FM - Sorbonne Université - Faculté de Médecine
17 Service de Dermatologie et Médecine Interne [Pointe-à-Pitre, Guadeloupe]

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.

Domaines: Sciences du Vivant [q-bio]

Audrey Aussy, Manuel Fréret, Laure Gallay, Didier Bessis, Thierry Vincent, et al.. The IgG2 Isotype of Anti–Transcription Intermediary Factor 1γ Autoantibodies Is a Biomarker of Cancer and Mortality in Adult Dermatomyositis. Arthritis & rheumatology, 2019, 71 (8), pp.1360-1370. ⟨10.1002/art.40895⟩. ⟨hal-02352134⟩