10 research outputs found
Dermatomyosites paranéoplasiques : rÎle des anticorps anti-TIF1gamma et du cancer dans le déclenchement de la dermatomyosite
Anti-TIF1g autoantibodies (aAb) are the main predictors of cancer in adult dermatomyositis (DM). As the cancer is a poor prognosis factor, the presence of anti-TIF1g aAb requires careful and repeated cancerinvestigations, while a substantial proportion of anti-TIF1g+ DM patients will never develop any cancer. Identification of biomarkers that accurately identify patients at risk is therefore relevant. In addition, theparaneoplastic nature of this form of DM encourages the analyze of the potential modifications of TIF1g atthe tumor level (somatic mutation, hyperexpression), which may lead to the generation of neoantigenspotentially responsible for triggering the immune response against TIF1g. The identification of such modifications would be helpful for the understanding of the DM pathogenesis. The objectives of this work were 1) to characterize anti-TIF1g aAb in a cohort of DM patients with or without cancer to identify biomarkers of cancer and 2) to sequence tumor DNA in patients with anti-TIF1g paraneoplastic DM to detect somatic mutations.Analysis of the characteristics of anti-TF1 aAb in 51 adult patients revealed that the presence of IgG2 anti-TIF1g is predictive of cancer occurrence and is a mortality biomarker. Cancer may be present in the group without IgG2 but having a better prognosis, with association between cancer remission and DMremission. Age older than 60 is a mortality factor independent of IgG2. Patients not showing cancer are younger, have mostly isolated anti-TIF1g IgG1 and have a chronic disease with brief relapses andremissions, characteristics similar to juvenile forms. The DM in adults and children do not have the samerepresentativeness as the anti-TIF1g isotypes, suggesting a distinct pathophysiological mechanism. The sequencing of TRIM33 gene encoding TIF1g was performed with NGS (Next generation sequencing) technology from the DNA of 15 tumors collected from 14 patients with anti-TIF1g DM. Four tumors from four patients (27%) showed somatic mutations of TRIM33 with allelic ratios greater than 5% in tumors DNA. A total of 18 somatic mutations were recorded. Nine are exon mutations, generating a newpeptide sequence; at least 5 mutations have a deleterious effect on splicing that may lead to the synthesis of a neoprotein. These mutations have to be confirmed by Sanger sequencing. HLA haplotyping of patientsis also required to analyze neoantigens binding to MHC molecules.Our findings indicate that IgG2 anti-TIF1g is a mortality biomarker and increase the risk of cancer in the paraneoplastic DM, and it has to be sought as soon as DM is diagnosed. DM subgroups defined by isotype raise the question of reflecting a different anti-tumor response between groups. This could be more effectivein the case of IgG1, or chronic in the case of IgG2. The small number of patients exhibiting point mutations is a point allowing to consider the modification of TIF1g protein as the trigger of the immune response. It also leads us to seek other mechanisms, such as hyperexpression. These results are consistent with different pathogenesis mechanisms according to either the presence or the absence of cancer.La dermatomyosite (DM) Ă auto-anticorps (aAc) anti-TIF1g est une forme de myopathie auto-immune trĂšs fortement associĂ©e au cancer chez lâadulte. Or le cancer est le facteur de mauvais pronostic de la DM et la prĂ©sence de lâaAc anti-TIF1g impose une recherche minutieuse et rĂ©pĂ©tĂ©e du cancer, alors que certains patients nâen dĂ©velopperont jamais. La recherche de biomarqueurs identifiant prĂ©cisĂ©ment les patients Ă risque est donc pertinente. Par ailleurs, le caractĂšre paranĂ©oplasique de cette forme de DM incite Ă rechercherdes modifications de TIF1g au niveau tumoral (mutation, hyper-expression), gĂ©nĂ©rant des nĂ©oantigĂšnes potentiellement responsable de lâinitiation dâune rĂ©ponse dirigĂ©e contre TIF1g. La mise en Ă©vidence de telles modifications permettrait dâavancer dans la comprĂ©hension des mĂ©canismes de la maladie. Les objectifs de ce travail Ă©taient 1) de caractĂ©riser les aAc anti-TIF1g dans une cohorte de patients atteints de DM avec ou sans cancer et 2) de sĂ©quencer lâADN tumoral de patients atteints de DM paranĂ©oplasique Ă aAc anti-TIF1g.Lâanalyse des caractĂ©ristiques des aAc anti-TIF1g de 51 patients adultes a rĂ©vĂ©lĂ© que la prĂ©sence dâIgG2anti-TIF1g est prĂ©dictive de lâassociation au cancer et est un biomarqueur de mortalitĂ©. Le cancer peut -ĂȘtreprĂ©sent mĂȘme en absence dâIgG2, mais il est de meilleur pronostic et sa rĂ©mission sâaccompagne dâunerĂ©mission de la DM. LâĂąge supĂ©rieur Ă 60 ans est un facteur de mortalitĂ© indĂ©pendant des IgG2. Les patients sans cancer sont plus jeunes, ont majoritairement des IgG1 anti-TIF1g isolĂ©s et ont une maladie dâĂ©volution chronique faite de poussĂ©es et de rĂ©missions brĂšves Ă lâimage des formes juvĂ©niles. Les DM de lâadulte et de lâenfant nâont dâailleurs pas la mĂȘme reprĂ©sentativitĂ© des isotypes anti-TIF1g, suggĂ©rant un mĂ©canismephysiopathologique distinct. Le sĂ©quençage du gĂšne TRIM33 codant pour TIF1g, a Ă©tĂ© rĂ©alisĂ© par NGS (Next generation sequencing)Ă partir de lâADN de 15 tumeurs provenant de 14 patients avec DM Ă aAc anti-TIF1g. Quatre tumeurs issues de quatre patients (27%) prĂ©sentent des mutations ponctuelles de TRIM33 avec ration allĂ©lique supĂ©rieurĂ 5% dans lâADN tumoral. Un total de 18 mutations par substitution a Ă©tĂ© comptabilisĂ©. Neuf sont des mutations dâexon, gĂ©nĂ©rant une nouvelle sĂ©quence peptidique ; au moins 5 mutations ont un effet dĂ©lĂ©tĂšre sur lâĂ©pissage avec probable production dâune nĂ©oprotĂ©ine. Ces mutations seront Ă confirmer par unsĂ©quençage Sanger. Le typage HLA des patients sera Ă©galement Ă rĂ©aliser pour modĂ©liser la liaison desnĂ©oantigĂšnes sur les molĂ©cules du complexe majeur dâhistocompatibilitĂ©.Ce travail a permis dâidentifier lâIgG2 anti-TIF1g comme un biomarqueur de mortalitĂ© et de risqueaccru de cancer au sein du groupe des DM paranĂ©oplasiques Ă TIF1g, qu'il convient de rechercher dĂšs lediagnostic de DM. La dĂ©finition de sous-groupes de DM selon lâisotype soulĂšve la question du reflet dâune rĂ©ponse antitumorale diffĂ©rente entre les groupes, qui pourrait ĂȘtre plus efficace dans le cas des IgG1, ou plus chronique dans le cas des IgG2. Le petit nombre de patients prĂ©sentant des mutations ponctuelles vadans le sens dâune modification de la protĂ©ine TIF1g Ă lâorigine de la rĂ©ponse immunitaire mais nous inciteĂ rechercher dâautres mĂ©canismes, telles que lâhyper-expression. Ces rĂ©sultats sont concordants avec desmĂ©canismes de pathogenĂšse diffĂ©rents entre enfants et adultes, et selon la prĂ©sence dâun cancer
Paraneoplastic dermatomyositis : role of anti-TIF1gamma antibodies and cancer in triggering dermatomyositis
La dermatomyosite (DM) Ă auto-anticorps (aAc) anti-TIF1g est une forme de myopathie auto-immune trĂšs fortement associĂ©e au cancer chez lâadulte. Or le cancer est le facteur de mauvais pronostic de la DM et la prĂ©sence de lâaAc anti-TIF1g impose une recherche minutieuse et rĂ©pĂ©tĂ©e du cancer, alors que certains patients nâen dĂ©velopperont jamais. La recherche de biomarqueurs identifiant prĂ©cisĂ©ment les patients Ă risque est donc pertinente. Par ailleurs, le caractĂšre paranĂ©oplasique de cette forme de DM incite Ă rechercherdes modifications de TIF1g au niveau tumoral (mutation, hyper-expression), gĂ©nĂ©rant des nĂ©oantigĂšnes potentiellement responsable de lâinitiation dâune rĂ©ponse dirigĂ©e contre TIF1g. La mise en Ă©vidence de telles modifications permettrait dâavancer dans la comprĂ©hension des mĂ©canismes de la maladie. Les objectifs de ce travail Ă©taient 1) de caractĂ©riser les aAc anti-TIF1g dans une cohorte de patients atteints de DM avec ou sans cancer et 2) de sĂ©quencer lâADN tumoral de patients atteints de DM paranĂ©oplasique Ă aAc anti-TIF1g.Lâanalyse des caractĂ©ristiques des aAc anti-TIF1g de 51 patients adultes a rĂ©vĂ©lĂ© que la prĂ©sence dâIgG2anti-TIF1g est prĂ©dictive de lâassociation au cancer et est un biomarqueur de mortalitĂ©. Le cancer peut -ĂȘtreprĂ©sent mĂȘme en absence dâIgG2, mais il est de meilleur pronostic et sa rĂ©mission sâaccompagne dâunerĂ©mission de la DM. LâĂąge supĂ©rieur Ă 60 ans est un facteur de mortalitĂ© indĂ©pendant des IgG2. Les patients sans cancer sont plus jeunes, ont majoritairement des IgG1 anti-TIF1g isolĂ©s et ont une maladie dâĂ©volution chronique faite de poussĂ©es et de rĂ©missions brĂšves Ă lâimage des formes juvĂ©niles. Les DM de lâadulte et de lâenfant nâont dâailleurs pas la mĂȘme reprĂ©sentativitĂ© des isotypes anti-TIF1g, suggĂ©rant un mĂ©canismephysiopathologique distinct. Le sĂ©quençage du gĂšne TRIM33 codant pour TIF1g, a Ă©tĂ© rĂ©alisĂ© par NGS (Next generation sequencing)Ă partir de lâADN de 15 tumeurs provenant de 14 patients avec DM Ă aAc anti-TIF1g. Quatre tumeurs issues de quatre patients (27%) prĂ©sentent des mutations ponctuelles de TRIM33 avec ration allĂ©lique supĂ©rieurĂ 5% dans lâADN tumoral. Un total de 18 mutations par substitution a Ă©tĂ© comptabilisĂ©. Neuf sont des mutations dâexon, gĂ©nĂ©rant une nouvelle sĂ©quence peptidique ; au moins 5 mutations ont un effet dĂ©lĂ©tĂšre sur lâĂ©pissage avec probable production dâune nĂ©oprotĂ©ine. Ces mutations seront Ă confirmer par unsĂ©quençage Sanger. Le typage HLA des patients sera Ă©galement Ă rĂ©aliser pour modĂ©liser la liaison desnĂ©oantigĂšnes sur les molĂ©cules du complexe majeur dâhistocompatibilitĂ©.Ce travail a permis dâidentifier lâIgG2 anti-TIF1g comme un biomarqueur de mortalitĂ© et de risqueaccru de cancer au sein du groupe des DM paranĂ©oplasiques Ă TIF1g, qu'il convient de rechercher dĂšs lediagnostic de DM. La dĂ©finition de sous-groupes de DM selon lâisotype soulĂšve la question du reflet dâune rĂ©ponse antitumorale diffĂ©rente entre les groupes, qui pourrait ĂȘtre plus efficace dans le cas des IgG1, ou plus chronique dans le cas des IgG2. Le petit nombre de patients prĂ©sentant des mutations ponctuelles vadans le sens dâune modification de la protĂ©ine TIF1g Ă lâorigine de la rĂ©ponse immunitaire mais nous inciteĂ rechercher dâautres mĂ©canismes, telles que lâhyper-expression. Ces rĂ©sultats sont concordants avec desmĂ©canismes de pathogenĂšse diffĂ©rents entre enfants et adultes, et selon la prĂ©sence dâun cancer.Anti-TIF1g autoantibodies (aAb) are the main predictors of cancer in adult dermatomyositis (DM). As the cancer is a poor prognosis factor, the presence of anti-TIF1g aAb requires careful and repeated cancerinvestigations, while a substantial proportion of anti-TIF1g+ DM patients will never develop any cancer. Identification of biomarkers that accurately identify patients at risk is therefore relevant. In addition, theparaneoplastic nature of this form of DM encourages the analyze of the potential modifications of TIF1g atthe tumor level (somatic mutation, hyperexpression), which may lead to the generation of neoantigenspotentially responsible for triggering the immune response against TIF1g. The identification of such modifications would be helpful for the understanding of the DM pathogenesis. The objectives of this work were 1) to characterize anti-TIF1g aAb in a cohort of DM patients with or without cancer to identify biomarkers of cancer and 2) to sequence tumor DNA in patients with anti-TIF1g paraneoplastic DM to detect somatic mutations.Analysis of the characteristics of anti-TF1 aAb in 51 adult patients revealed that the presence of IgG2 anti-TIF1g is predictive of cancer occurrence and is a mortality biomarker. Cancer may be present in the group without IgG2 but having a better prognosis, with association between cancer remission and DMremission. Age older than 60 is a mortality factor independent of IgG2. Patients not showing cancer are younger, have mostly isolated anti-TIF1g IgG1 and have a chronic disease with brief relapses andremissions, characteristics similar to juvenile forms. The DM in adults and children do not have the samerepresentativeness as the anti-TIF1g isotypes, suggesting a distinct pathophysiological mechanism. The sequencing of TRIM33 gene encoding TIF1g was performed with NGS (Next generation sequencing) technology from the DNA of 15 tumors collected from 14 patients with anti-TIF1g DM. Four tumors from four patients (27%) showed somatic mutations of TRIM33 with allelic ratios greater than 5% in tumors DNA. A total of 18 somatic mutations were recorded. Nine are exon mutations, generating a newpeptide sequence; at least 5 mutations have a deleterious effect on splicing that may lead to the synthesis of a neoprotein. These mutations have to be confirmed by Sanger sequencing. HLA haplotyping of patientsis also required to analyze neoantigens binding to MHC molecules.Our findings indicate that IgG2 anti-TIF1g is a mortality biomarker and increase the risk of cancer in the paraneoplastic DM, and it has to be sought as soon as DM is diagnosed. DM subgroups defined by isotype raise the question of reflecting a different anti-tumor response between groups. This could be more effectivein the case of IgG1, or chronic in the case of IgG2. The small number of patients exhibiting point mutations is a point allowing to consider the modification of TIF1g protein as the trigger of the immune response. It also leads us to seek other mechanisms, such as hyperexpression. These results are consistent with different pathogenesis mechanisms according to either the presence or the absence of cancer
Dermatomyosites paranéoplasiques : rÎle des anticorps anti-TIF1gamma et du cancer dans le déclenchement de la dermatomyosite
Anti-TIF1g autoantibodies (aAb) are the main predictors of cancer in adult dermatomyositis (DM). As the cancer is a poor prognosis factor, the presence of anti-TIF1g aAb requires careful and repeated cancerinvestigations, while a substantial proportion of anti-TIF1g+ DM patients will never develop any cancer. Identification of biomarkers that accurately identify patients at risk is therefore relevant. In addition, theparaneoplastic nature of this form of DM encourages the analyze of the potential modifications of TIF1g atthe tumor level (somatic mutation, hyperexpression), which may lead to the generation of neoantigenspotentially responsible for triggering the immune response against TIF1g. The identification of such modifications would be helpful for the understanding of the DM pathogenesis. The objectives of this work were 1) to characterize anti-TIF1g aAb in a cohort of DM patients with or without cancer to identify biomarkers of cancer and 2) to sequence tumor DNA in patients with anti-TIF1g paraneoplastic DM to detect somatic mutations.Analysis of the characteristics of anti-TF1 aAb in 51 adult patients revealed that the presence of IgG2 anti-TIF1g is predictive of cancer occurrence and is a mortality biomarker. Cancer may be present in the group without IgG2 but having a better prognosis, with association between cancer remission and DMremission. Age older than 60 is a mortality factor independent of IgG2. Patients not showing cancer are younger, have mostly isolated anti-TIF1g IgG1 and have a chronic disease with brief relapses andremissions, characteristics similar to juvenile forms. The DM in adults and children do not have the samerepresentativeness as the anti-TIF1g isotypes, suggesting a distinct pathophysiological mechanism. The sequencing of TRIM33 gene encoding TIF1g was performed with NGS (Next generation sequencing) technology from the DNA of 15 tumors collected from 14 patients with anti-TIF1g DM. Four tumors from four patients (27%) showed somatic mutations of TRIM33 with allelic ratios greater than 5% in tumors DNA. A total of 18 somatic mutations were recorded. Nine are exon mutations, generating a newpeptide sequence; at least 5 mutations have a deleterious effect on splicing that may lead to the synthesis of a neoprotein. These mutations have to be confirmed by Sanger sequencing. HLA haplotyping of patientsis also required to analyze neoantigens binding to MHC molecules.Our findings indicate that IgG2 anti-TIF1g is a mortality biomarker and increase the risk of cancer in the paraneoplastic DM, and it has to be sought as soon as DM is diagnosed. DM subgroups defined by isotype raise the question of reflecting a different anti-tumor response between groups. This could be more effectivein the case of IgG1, or chronic in the case of IgG2. The small number of patients exhibiting point mutations is a point allowing to consider the modification of TIF1g protein as the trigger of the immune response. It also leads us to seek other mechanisms, such as hyperexpression. These results are consistent with different pathogenesis mechanisms according to either the presence or the absence of cancer.La dermatomyosite (DM) Ă auto-anticorps (aAc) anti-TIF1g est une forme de myopathie auto-immune trĂšs fortement associĂ©e au cancer chez lâadulte. Or le cancer est le facteur de mauvais pronostic de la DM et la prĂ©sence de lâaAc anti-TIF1g impose une recherche minutieuse et rĂ©pĂ©tĂ©e du cancer, alors que certains patients nâen dĂ©velopperont jamais. La recherche de biomarqueurs identifiant prĂ©cisĂ©ment les patients Ă risque est donc pertinente. Par ailleurs, le caractĂšre paranĂ©oplasique de cette forme de DM incite Ă rechercherdes modifications de TIF1g au niveau tumoral (mutation, hyper-expression), gĂ©nĂ©rant des nĂ©oantigĂšnes potentiellement responsable de lâinitiation dâune rĂ©ponse dirigĂ©e contre TIF1g. La mise en Ă©vidence de telles modifications permettrait dâavancer dans la comprĂ©hension des mĂ©canismes de la maladie. Les objectifs de ce travail Ă©taient 1) de caractĂ©riser les aAc anti-TIF1g dans une cohorte de patients atteints de DM avec ou sans cancer et 2) de sĂ©quencer lâADN tumoral de patients atteints de DM paranĂ©oplasique Ă aAc anti-TIF1g.Lâanalyse des caractĂ©ristiques des aAc anti-TIF1g de 51 patients adultes a rĂ©vĂ©lĂ© que la prĂ©sence dâIgG2anti-TIF1g est prĂ©dictive de lâassociation au cancer et est un biomarqueur de mortalitĂ©. Le cancer peut -ĂȘtreprĂ©sent mĂȘme en absence dâIgG2, mais il est de meilleur pronostic et sa rĂ©mission sâaccompagne dâunerĂ©mission de la DM. LâĂąge supĂ©rieur Ă 60 ans est un facteur de mortalitĂ© indĂ©pendant des IgG2. Les patients sans cancer sont plus jeunes, ont majoritairement des IgG1 anti-TIF1g isolĂ©s et ont une maladie dâĂ©volution chronique faite de poussĂ©es et de rĂ©missions brĂšves Ă lâimage des formes juvĂ©niles. Les DM de lâadulte et de lâenfant nâont dâailleurs pas la mĂȘme reprĂ©sentativitĂ© des isotypes anti-TIF1g, suggĂ©rant un mĂ©canismephysiopathologique distinct. Le sĂ©quençage du gĂšne TRIM33 codant pour TIF1g, a Ă©tĂ© rĂ©alisĂ© par NGS (Next generation sequencing)Ă partir de lâADN de 15 tumeurs provenant de 14 patients avec DM Ă aAc anti-TIF1g. Quatre tumeurs issues de quatre patients (27%) prĂ©sentent des mutations ponctuelles de TRIM33 avec ration allĂ©lique supĂ©rieurĂ 5% dans lâADN tumoral. Un total de 18 mutations par substitution a Ă©tĂ© comptabilisĂ©. Neuf sont des mutations dâexon, gĂ©nĂ©rant une nouvelle sĂ©quence peptidique ; au moins 5 mutations ont un effet dĂ©lĂ©tĂšre sur lâĂ©pissage avec probable production dâune nĂ©oprotĂ©ine. Ces mutations seront Ă confirmer par unsĂ©quençage Sanger. Le typage HLA des patients sera Ă©galement Ă rĂ©aliser pour modĂ©liser la liaison desnĂ©oantigĂšnes sur les molĂ©cules du complexe majeur dâhistocompatibilitĂ©.Ce travail a permis dâidentifier lâIgG2 anti-TIF1g comme un biomarqueur de mortalitĂ© et de risqueaccru de cancer au sein du groupe des DM paranĂ©oplasiques Ă TIF1g, qu'il convient de rechercher dĂšs lediagnostic de DM. La dĂ©finition de sous-groupes de DM selon lâisotype soulĂšve la question du reflet dâune rĂ©ponse antitumorale diffĂ©rente entre les groupes, qui pourrait ĂȘtre plus efficace dans le cas des IgG1, ou plus chronique dans le cas des IgG2. Le petit nombre de patients prĂ©sentant des mutations ponctuelles vadans le sens dâune modification de la protĂ©ine TIF1g Ă lâorigine de la rĂ©ponse immunitaire mais nous inciteĂ rechercher dâautres mĂ©canismes, telles que lâhyper-expression. Ces rĂ©sultats sont concordants avec desmĂ©canismes de pathogenĂšse diffĂ©rents entre enfants et adultes, et selon la prĂ©sence dâun cancer
Dermatomyositis and Immune-Mediated Necrotizing Myopathies: A Window on Autoimmunity and Cancer
International audienc
Dermatomyositis and Immune-Mediated Necrotizing Myopathies: A Window on Autoimmunity and Cancer
Autoimmune myopathies (myositides) are strongly associated with malignancy. The link between myositis and cancer, originally noticed by Bohan and Peter in their classification in 1975 (1), has been evidenced by large population-based cohort studies and a recent meta-analysis. The numerous reports of cases in which the clinical course of myositis reflects that of cancer and the short delay between myositis and cancer onset support the notion that myositis may be an authentic paraneoplastic disorder. Thus, cancer-associated myositis raises the question of cancer as a cause rather than a consequence of autoimmunity. Among myositides, dermatomyositis and more recently, although to a lesser extent, immune-mediated necrotizing myopathies are the most documented forms associated with cancer. Interestingly, the current diagnostic approach for myositis is based on the identification of specific antibodies where each antibody determines specific clinical features and outcomes. Recent findings have shown that the autoantibodies anti-TIF1Îł, anti-NXP2 and anti-HMGCR are associated with cancers in the course of myositis. Herein, we highlight the fact that the targets of these three autoantibodies involve cellular pathways that intervene in tumor promotion and we discuss the role of cancer mutations as autoimmunity triggers in adult myositis
The IgG2 isotype of anti-transcription intermediary factor 1-gamma autoantibodies is a biomarker of mortality and cancer in adult dermatomyositis
International audienc
Consensus gene modules strategy identifies candidate blood-based biomarkers for primary Sjogren's disease
Primary Sjogren disease (pSD) is an autoimmune disease characterized by lymphoid infiltration of exocrine glands leading to dryness of the mucosal surfaces and by the production of autoantibodies. The pathophysiology of pSD remains elusive and no treatment with demonstrated efficacy is available yet. To better understand the biology underlying pSD heterogeneity, we aimed at identifying Consensus gene Modules (CMs) that summarize the high-dimensional transcriptomic data of whole blood samples in pSD patients. We performed unsupervised gene classification on four data sets and identified thirteen CMs. We annotated and interpreted each of these CMs as corresponding to cell type abundances or biological functions by using gene set enrichment analyses and transcriptomic profiles of sorted blood cell subsets. Correlation with independently measured cell type abundances by flow cytometry confirmed these annotations. We used these CMs to reconcile previously proposed patient stratifications of pSD. Importantly, we showed that the expression of modules representing lymphocytes and erythrocytes before treatment initiation is associated with response to hydroxychloroquine and leflunomide combination therapy in a clinical trial. These consensus modules will help the identification and translation of blood-based predictive biomarkers for the treatment of pSD
The IgG2 Isotype of AntiâTranscription Intermediary Factor 1Îł Autoantibodies Is a Biomarker of Cancer and Mortality in Adult Dermatomyositis
International audienceObjective: 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 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