Closing in on environmental causes for autoimmune diseases

Below is an identical twins study of identical twins with identical DNA and indentical genes however ONLY ONE has autoimmune disease.

The problem is as we age and are exposed to environmental insults, chemicals, disease etc, these insults change the way are genes work. This change in function is called an epigenetic change. The genes remain the same but something affects their ability to function.

In this study one twin had genes whose functions were changed to cause autoimmune disease and the other twin did not.

These Cold Springs Harbor researchers were able to determine the difference in gene function that lead to autoimmune disease in this case lupus.

The next step is to find out what causes the changes--those pesky environmental insults-- and then how to reverse those changes to get normal HEALTHY gene function back again.

We know that autoimmune disease turns on suddenly. It likely can be turned off just as quickly when we find the right switches which our friends at Cold Harbor have done. Next let's get those switches back on and all of us back to good health.

There are already a class of drugs that can reverse changes to genes that go by the acronym HDAC. We need a lot more work done on these drugs so they can target specific parts of our genes that need turning back on.

Finding the gene that have been affected to cause autoimmune disease is a big step forward.

Come on researchers let's get to the cures sooner than later. Get those genes turned on again.

Good job Cold Harbor Laboratory on this first big step.



Cold Spring Harbor Laboratory
Genomes of identical twins reveal epigenetic changes that may play role in lupus
Identical twins look the same and are nearly genetically identical, but environmental factors and the resulting cellular changes could cause disease in one sibling and not the other. In a study published online in Genome Research (www.genome.org), scientists have studied twins discordant for the autoimmune disease lupus, mapping DNA modifications across the genome and shedding light on epigenetic changes that may play a role in the disease.

Because the genetic makeup of monozygotic twins (commonly known as identical twins) is nearly identical, phenotypic traits and heritable diseases are often concordant, manifesting in both siblings. However, some phenotypes and diseases such as autoimmune disease can arise in only one sibling, suggesting other factors such as environment likely play a role in determining phenotypic differences.

Epigenetic modifications, cellular changes that can influence expression of genes, are now widely recognized to influence phenotype and frequently occur in disease. Furthermore, environmental factors such as diet and chemical exposure can change the epigenetic status of genes. Recent research has identified epigenetic modifications at several aberrantly regulated genes in autoimmune diseases such as systemic lupus erythematosus (SLE), and other studies have suggested that epigenetic differences are associated with phenotypic discordance between identical twins.

In this work, researchers from Spain and the United States performed the first genome-wide high-throughput analysis of a specific epigenetic modification, DNA methylation, in the context of autoimmune disease. Taking advantage of the identical genetic background in monozygotic twins, the group directly compared DNA methylation in healthy twins and twins discordant for autoimmune diseases, including SLE, looking for changes that could be related to pathogenesis in one sibling and not the other.

In the case of SLE, the group found widespread changes in DNA methylation status at a significant number of genes. Dr. Esteban Ballestar, senior author of the study, noted that this is the largest number of genes exhibiting DNA methylation changes observed in an autoimmune disease to date, and includes genes previously implicated in SLE pathogenesis. Importantly, Ballestar's team found that a significant number of the novel differentially methylated genes are related to multiple immune system functions and are potentially linked to SLE.

"Our study suggests that the effect of the environment or differences in lifestyle may leave a molecular mark in key genes for immune function that contributes to the differential onset of the disease in twins," Ballestar said. Most studies of DNA methylation and human disease have been in the context of cancer research, Ballestar noted, and he hopes that this work will attract more researchers to also investigate DNA methylation alterations in autoimmune disease and other disorders for the development of therapies.
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Scientists from Bellvitge Biomedical Research Institute (Barcelona, Spain), Christian-Albrechts-University Kiel (Kiel, Germany), Centro de Investigacion Principe Felipe (Valencia, Spain), the Broad Institute of MIT and Harvard (Cambridge, MA), Brigham and Women's Hospital (Brookline, MA), the National Institute of Environmental Health Sciences (Bethesda, MD), Gregorio Marañon Hospital (Madrid, Spain), ISCIII Center for Biomedical Research on Rare Diseases (Valencia, Spain), Institut de Medicina Predictiva i Personalitzada del Càncer (Badalona, Spain), and the University of Oklahoma Health Sciences Center (Oklahoma City, OK) contributed to this study.
This work was supported by the Spanish Ministry of Science and Innovation, the National Institute of Environmental Health Sciences, the National Institutes of Health, the Alliance for Lupus Research, the US Department of Veterans Affairs, and a BEFI Predoctoral Fellowship from the Carlos III Health Institute, Spain.
Media contacts:
Esteban Ballestar, Ph.D. (Bellvitge Biomedical Research Institute; eballestar@idibell.cat, +34 932607133) and Diomaris Gonzalez (Alliance for Lupus Research; dgonzalez@lupusresearch.org) have agreed to be contacted for more information.
Interested reporters may obtain copies of the manuscript from the Genome Research Editorial Office (genomere@cshl.edu; +1-516-422-4012).
About the article:
The manuscript will be published online ahead of print on December 22, 2009. Its full citation is as follows: Javierre BM, Fernandez AF, Richter J, Al-Shahrour F, Martin-Subero JI, Rodriguez-Ubreva J, Berdasco M, Fraga MF, O'Hanlon TP, Rider LG, Jacinto FV, Lopez-Longo FJ, Dopazo J, Forn M, Peinado MA, Carreño L, Sawalha AH, Harley JB, Siebert R, Esteller M, Miller FW, Ballestar E. Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Res doi:10.1101/gr.100289.109.
About Genome Research:
Launched in 1995, Genome Research (www.genome.org) is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies.

About Cold Spring Harbor Laboratory Press:
Cold Spring Harbor Laboratory is a private, nonprofit institution in New York that conducts research in cancer and other life sciences and has a variety of educational programs. Its Press, originating in 1933, is the largest of the Laboratory's five education divisions and is a publisher of books, journals, and electronic media for scientists, students, and the general public.
Genome Research issues press releases to highlight significant research studies that are published in the journal.