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

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.

239th ENMC International Workshop: Classification of dermatomyositis, Amsterdam, the Netherlands, 14–16 December 2018

“…Interestingly age at onset also seems to play a role in such associations, with one clear example being calcinosis which is associated with a positive NXP2 MSA but also closely correlated with age of onset of disease [112] . In contrast the TIF1-γ autoantibody appears to be associated with risk of cancer in adults but not in children and a recent study of the isotype of TIF1-γ autoantibodies in adults and children suggests that the cancer risk may associate with specific isotype of anti-TIF1-γ autoantibodies [87] . A recent genetic analysis also suggests that unlike previous data for other MSAs, the HLA genetic associations for adult and paediatric onset cases of TIF1-γ positive IIM may also differ [113] .…”

“…He next reported on his group's recent investigations aimed at determining whether a distinct type of anti-TIF1-γ autoantibody response, different from that seen in juvenile DM, might be associated with cancer among adult DM patients [87] . For this, his group developed a quantitative anti-TIF1-γ Addressable Laser Bead Immuno-Assay (ALBIA) that allows for the determination of autoantibody levels and isotypes.…”

Anti-TIF1-γ autoantibodies: warning lights of a tumour autoantigen

“…Moreover, patients with an age ≥ 39 and anti-TIF1-γ autoantibodies had a significantly higher risk of developing cancer compared with those under 39 years old [11]. In a recent study, IgG2 autoantibodies in specific were associated with mortality [62]. Given the strong association between anti-TIF1-γ and cancer-associated DM in older patients, rigorous surveillance and screening for cancer in these patients is advised as cancer is the main prognostic factor in IIMs [63].…”

Dermatomiositis como síndrome paraneoplásico

“…(10)(11)(12)16). En un reciente estudio, con base en la duda de por qué un porcentaje de los pacientes con anti TIF1 no presentan neoplasia, propusieron el isotipo IgG2 de este anticuerpo y encontraron para el mismo un valor predictivo positivo del 100%, por lo que proponen el uso de este nuevo biomarcador (19). La proteína TIF1 e534 tiene diversas funciones relacionadas con la embriogénesis, hematopoyesis, mitosis y regulación del ciclo celular, reparación del ADN, inmunidad innata y adaptativa, diferenciación de osteoblastos, transcripción viral y oncogénesis en caso de disregulación (11,16).…”