Arron Munggela Foma1, Saeed Aslani1,2, Jafar Karami2,3, Ahmadreza Jamshidi2, Mahdi Mahmoudi4. 1. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2. Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran. 3. Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. 4. Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran. mahmoudim@tums.ac.ir.
Abstract
BACKGROUND: Recent researches in the field of genetics have extended our knowledge through the discovery of genetic factors associated with autoimmune diseases (AID). Genetics by itself, however, cannot elucidate all the uncertainties encountered in the etiopathology of AID. On the other hand, incomplete harmony in the prevalence of AID in identical twins suggests that non-genetic factors may play an important role in determining the disease susceptibility. Besides, epigenetics, which is defined by changes in gene expression without a corresponding change in the DNA sequences, has come in to provide new awareness in the disease etiopathology by bridging the genetic and epigenetic factors. The recent advances in the field of epigenetics provide a new insight into the understanding of the disease mechanisms, development, diagnostic and prognostic approaches, as well as the various treatment methods. PURPOSE: This review paper aims to present an overview of epigenetic modifications involved in the pathogenesis of systemic lupus erythematosus (SLE) and discuss their important roles in clinical and pharmacological settings, including novel and recent therapeutic applications. RESULTS: Nowadays, it is believed that autoimmune diseases, such as SLE, begin when genetically susceptible factors associate with environmental triggers. The current therapeutic approaches for SLE treatment have been based on treatments with immunosuppressive drugs, which are linked to various side effects. It is difficult to develop highly effective treatments for SLE patients with minimal or no side effects, mainly due to the disease complexity. The breakthrough of pharmacoepigenetics provides a new approach to solve this problem. Epigenetic modifications can influence the efficacy of drugs by changing the gene expression through modifying chromatin remodeling. In this regard, epigenetic studies in SLE are expected to reveal novel disease biomarkers and therapeutic targets. CONCLUSIONS: Accumulating evidence disclosed that epigenetic dysregulations are engaged in SLE pathogenesis and may be exerted as biomarkers to diagnose and as tools to treat these patients.
BACKGROUND: Recent researches in the field of genetics have extended our knowledge through the discovery of genetic factors associated with autoimmune diseases (AID). Genetics by itself, however, cannot elucidate all the uncertainties encountered in the etiopathology of AID. On the other hand, incomplete harmony in the prevalence of AID in identical twins suggests that non-genetic factors may play an important role in determining the disease susceptibility. Besides, epigenetics, which is defined by changes in gene expression without a corresponding change in the DNA sequences, has come in to provide new awareness in the disease etiopathology by bridging the genetic and epigenetic factors. The recent advances in the field of epigenetics provide a new insight into the understanding of the disease mechanisms, development, diagnostic and prognostic approaches, as well as the various treatment methods. PURPOSE: This review paper aims to present an overview of epigenetic modifications involved in the pathogenesis of systemic lupus erythematosus (SLE) and discuss their important roles in clinical and pharmacological settings, including novel and recent therapeutic applications. RESULTS: Nowadays, it is believed that autoimmune diseases, such as SLE, begin when genetically susceptible factors associate with environmental triggers. The current therapeutic approaches for SLE treatment have been based on treatments with immunosuppressive drugs, which are linked to various side effects. It is difficult to develop highly effective treatments for SLEpatients with minimal or no side effects, mainly due to the disease complexity. The breakthrough of pharmacoepigenetics provides a new approach to solve this problem. Epigenetic modifications can influence the efficacy of drugs by changing the gene expression through modifying chromatin remodeling. In this regard, epigenetic studies in SLE are expected to reveal novel disease biomarkers and therapeutic targets. CONCLUSIONS: Accumulating evidence disclosed that epigenetic dysregulations are engaged in SLE pathogenesis and may be exerted as biomarkers to diagnose and as tools to treat these patients.
Authors: Anirudh J Ullal; Charles F Reich; Megan Clowse; Lisa G Criscione-Schreiber; Martin Tochacek; Marc Monestier; David S Pisetsky Journal: J Autoimmun Date: 2011-03-03 Impact factor: 7.094