07:41am Tuesday 24 October 2017

UTHealth scientists zeroing in on genes tied to two immune disorders

TARGETED RESEQUENCING OF IMMUNE-ASSOCIATED GENES – UTHealth researcher Xiaodong Zhou, M.D., will perform a study of the human leukocyte antigen (HLA) genomics of ankylosing spondylitis and scleroderma.

TARGETED RESEQUENCING OF IMMUNE-ASSOCIATED GENES - UTHealth researcher Xiaodong Zhou, M.D., will perform a study of the human leukocyte antigen (HLA) genomics of ankylosing spondylitis and scleroderma.The genes are thought to be associated with ankylosing spondylitis, a form of arthritis that attacks the spine, and systemic sclerosis (scleroderma), a chronic, often progressive, disease of connective tissue. As many as 2.4 million people in the United States may be affected by ankylosing spondylitis and its related diseases. Systemic sclerosis impacts about 100,000 people in the United States.

The researchers plan to conduct an exhaustive analysis of these genes and others using a research technique called targeted resequencing. The study will involve more than 6,000 patients with ankylosing spondylitis or scleroderma from the United States, China and Spain and it will focus on an area of the genome linked to immunity issues called the major histocompatibility complex. The study will also include about 3,000 people without the conditions.

“This is the most complicated region of the human genome,” said Xiaodong Zhou, M.D., a principal investigator and associate professor of internal medicine at the UTHealth Medical School. “The region contains genes linked to all types of immune diseases. In many instances, we don’t know precisely where the linkage comes from. We want to find out if these are true associations.”

Zhou, director of the UTHealth Research Laboratory in Rheumatology and Clinical Immunogenetics, said, “You need distinct ethnic populations for comparison purposes.”

While the immune system’s function is to protect the body, problems can occur. Immune systems can also induce inflammation, which is called autoinflammatory. Immune systems can also generate autoantibodies that can attack their own cells – a condition called autoimmune disease. Ankylosing spondylitis is an inflammatory disease and scleroderma is an autoimmune disorder.

Many genes linked to ankylosing spondylitis and scleroderma were identified with a research technique called a genome-wide association study in which scientists compare the genetic makeup of people with a certain disease to those without the disease. This technique shows researchers where to look for disease-associated genes in the human genome.

INTERCONTINENTAL STUDY OF TWO IMMUNE DISEASES- UTHealth immune disease researchers John D. Reveille, M.D., and Maureen D. Mayes, M.D., are zeroing in on genetic factors affecting two immune disorders.

INTERCONTINENTAL STUDY OF TWO IMMUNE DISEASES- UTHealth immune disease researchers John D. Reveille, M.D., and Maureen D. Mayes, M.D., are zeroing in on genetic factors affecting two immune disorders.

Several of the gene regions, each containing multiple genes, were discovered by the two other principal investigators in the study, John D. Reveille, M.D., and Maureen D. Mayes, M.D., M.P.H.

“We are taking our research to the next step,” said Reveille, holder of the George S. Bruce, Jr. Professorship in Arthritis and Other Rheumatic Diseases and the Linda and Ronny Finger Foundation Distinguished Chair in Neuroimmunologic Disorders at the UTHealth Medical School. “These new tests will help us better understand the causes of these diseases.”

Reveille, who is the chief of rheumatology at Memorial Hermann – Texas Medical Center, said researchers have identified many of the genetic components of ankylosing spondylitis.

Mayes, a professor of rheumatology at the UTHealth Medical School, said, “If we can find out which genes are responsible for these problems, we could potentially develop drugs to block their activity. These tests will also help us determine which combination of genes may be responsible for these illnesses.”

Mayes, who is the principal investigator of the NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases-funded Genome-Wide Association Study in Systemic Sclerosis, said researchers are about a quarter of the way to finding the genes and pathways responsible for systemic sclerosis.

By comparing immune-related genes of different populations, the scientists think they will be able to zero in on the most critical genes tied to ankylosing spondylitis and scleroderma, Mayes said. “Genes can vary from continent to continent. For example, there is a gene variant in Africa that confers resistance to malaria. That is not as common in the United States,” she said. “Where these genes overlap is of special interest to us.”

Zhou, Reveille and Mayes already have access to the DNA information of patients with ankylosing spondylitis and scleroderma from established cohorts from their previous studies in both Spain and the United States.

Later this year, the researchers will travel to China to coordinate the recruitment of people with these immune disorders with the aid of Jiucun Wang, Ph.D., of Fudan University in Shanghai and Hejian Zou, M.D., Ph.D. of Huashan Hospital in Shanghai, who both will lead the Chinese effort.

Their research is titled “Studies of HLA Region Genomics in Systemic Sclerosis and Ankylosing Spondylitis.” Their work is supported by a National Institutes of Health (NIH) grant covering $2 million in direct cost over five years.

Rob Cahill
Media Hotline: 713-500-3030


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