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Periodical determination of anti-TIF1γ in adult DM patients without CAM: a new approach on the study of CAM pathogeneses and its screening

Background: Dermatomyositis (DM) is the idiopathic inflammatory myopathy most associated to malignancy, being present in around 30% of the patients. Anti-TIF1γ is a myositis specific antibody (MSA) that is almost only present in DM patients. It is present in 73% of the cases of cancer-associated myositis (CAM). Nowadays, a single test of this antibody is carried out in order to detect a subset of patients diagnosed of DM who may have a higher likelihood to develop cancer, and therefore, will need accurate cancer surveillance. Some MSA have been noticed to be present in both, muscle-regenerating cells and in cancers known to be associated with CAM. It has been suggested that myositis is the consequence of a cross-react immunity, which originally targeted cancer cells, that fights against regenerating-muscle cells that originally targeted cancer cells. Since anti-TIF1γ is so highly associated with CAM in prevalence studies of the antibody, it is reasonable to think that TIF1γ may play a role in the pathogenesis of cancer in DM patients. Hence, we consider necessary to study the anti-TIF1γ behaviour along time to study its possible relationship with the tumorigenesis process. The aim of this study is to go forward on the understanding of cancer and DM pathogenesis in order to develop more specific therapies on both processes. Simultaneously, this study will provide information on the possible development of a more accurate cancer surveillance protocol in DM patients. Objectives: To determine whether there are changes from a first positive anti-TIF1γ value to a negative one or vice versa by performing periodical anti-TIF1γ serum analyses in adult DM patients without CAM criteria after the disease onset. Furthermore, we will also analyse whether these changes between the first serum analysis and the following are somehow associated to a different relative risk to develop cancer compared to the patients who do not have changes in their serum values. Methods: This study is a multicentre prospective cohort study that includes recently diagnosed DM patients without CAM criteria. Patient’s recruitment will last three years. There will be four groups of patients. 14 participants are needed in the group of patients with changes form a positive anti-TIF1γ value to a negative one; 22 participants are required in the group of patients with persistent positive anti-TIF1γ; 10 participants are needed in the group of patients with a change from a negative anti-TIF1γ value to a positive one; finally, 118 participants are required in the group of patients with persistent negative anti-TIF1γ values. Participants will be evaluated for a five-year follow-up period in order to compare the cancer incidence between patients with positive values of anti-TIF1γ and patients with negative values of the antibody. Anti-TIF1γ will be analysed by ELISA in absorbance units and confirmed by immunoblot. Cancer occurrence data will be registered by each physician when it is diagnosed. The results will be expressed as percentages for categorical variables. Continuous variables will be expressed as mean +/- SD if they are normally distributed or median (quartiles) if they are not. Bivariate analysis will be performed with X2 test and the Fisher test, and Cox regression analysis will be used to perform the multivariate analysis

Director: Selva O’Callaghan, Albert
Altres contribucions: Universitat de Girona. Facultat de Medicina
Autor: Maura Prat, Anna
Resum: Background: Dermatomyositis (DM) is the idiopathic inflammatory myopathy most associated to malignancy, being present in around 30% of the patients. Anti-TIF1γ is a myositis specific antibody (MSA) that is almost only present in DM patients. It is present in 73% of the cases of cancer-associated myositis (CAM). Nowadays, a single test of this antibody is carried out in order to detect a subset of patients diagnosed of DM who may have a higher likelihood to develop cancer, and therefore, will need accurate cancer surveillance. Some MSA have been noticed to be present in both, muscle-regenerating cells and in cancers known to be associated with CAM. It has been suggested that myositis is the consequence of a cross-react immunity, which originally targeted cancer cells, that fights against regenerating-muscle cells that originally targeted cancer cells. Since anti-TIF1γ is so highly associated with CAM in prevalence studies of the antibody, it is reasonable to think that TIF1γ may play a role in the pathogenesis of cancer in DM patients. Hence, we consider necessary to study the anti-TIF1γ behaviour along time to study its possible relationship with the tumorigenesis process. The aim of this study is to go forward on the understanding of cancer and DM pathogenesis in order to develop more specific therapies on both processes. Simultaneously, this study will provide information on the possible development of a more accurate cancer surveillance protocol in DM patients. Objectives: To determine whether there are changes from a first positive anti-TIF1γ value to a negative one or vice versa by performing periodical anti-TIF1γ serum analyses in adult DM patients without CAM criteria after the disease onset. Furthermore, we will also analyse whether these changes between the first serum analysis and the following are somehow associated to a different relative risk to develop cancer compared to the patients who do not have changes in their serum values. Methods: This study is a multicentre prospective cohort study that includes recently diagnosed DM patients without CAM criteria. Patient’s recruitment will last three years. There will be four groups of patients. 14 participants are needed in the group of patients with changes form a positive anti-TIF1γ value to a negative one; 22 participants are required in the group of patients with persistent positive anti-TIF1γ; 10 participants are needed in the group of patients with a change from a negative anti-TIF1γ value to a positive one; finally, 118 participants are required in the group of patients with persistent negative anti-TIF1γ values. Participants will be evaluated for a five-year follow-up period in order to compare the cancer incidence between patients with positive values of anti-TIF1γ and patients with negative values of the antibody. Anti-TIF1γ will be analysed by ELISA in absorbance units and confirmed by immunoblot. Cancer occurrence data will be registered by each physician when it is diagnosed. The results will be expressed as percentages for categorical variables. Continuous variables will be expressed as mean +/- SD if they are normally distributed or median (quartiles) if they are not. Bivariate analysis will be performed with X2 test and the Fisher test, and Cox regression analysis will be used to perform the multivariate analysis
Accés al document: http://hdl.handle.net/2072/298230
Llenguatge: eng
Drets: Attribution-NonCommercial-NoDerivs 3.0 Spain
URI Drets: http://creativecommons.org/licenses/by-nc-nd/3.0/es/
Matèria: Dermatomiositis
Dermatomyositis
Antígens
Antigens
Càncer
Cancer
Títol: Periodical determination of anti-TIF1γ in adult DM patients without CAM: a new approach on the study of CAM pathogeneses and its screening
Tipus: info:eu-repo/semantics/bachelorThesis
Repositori: Recercat

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