Grandpa’s bad back turns out to be ankylosing spondylitis, then Aunt Ellen is diagnosed with lupus. In the next generation, Bud’s swollen fingers are the first signs of rheumatoid arthritis, and cousin Elizabeth’s stomach pains become Crohn’s disease. Her daughter Sara gets a double dose of the family inheritance with type 1 diabetes and thyroid problems.

“There seem to be family clusters of autoimmune illnesses. Certain genes overlap in predisposing individuals to these illnesses,” Director of UAB Division of Clinical Immunology and Rheumatology S. Louis Bridges, Jr., MD PhD, said. “Multiple autoimmune disorders share the same section of genetic code. But the upside of the overlap is that as we learn more about the genetics of these disorders and how they develop, diagnostic and therapeutic efforts that work for one may work for another.

“Autoimmune diseases seem to arise from a combination of genetic and environmental factors that turn those genes on and off. We can’t measure or predict all the environmental factors, but we can get a sense of risk by looking at an individual’s genetic profile.”

                  Bridges, whose primary interest is rheumatoid arthritis, has been studying the differences in the genetics of the disorder in black populations that grew up in rural areas of Africa.

                  “There were reports that rheumatoid arthritis was less common in black populations in those areas. The question was, does that difference come from a different environment, or a different genetic basis in that population than in Caucasians and Asians?” Bridges said.

“The major risk for rheumatoid arthritis is in the HLA genes in the MHC regions. We found that it was in the same regions in African black people as in Caucasians and Asians, but it was less common.”

Bridges said that by determining which genes and environmental influences cause autoimmune diseases, researchers hope to learn how to perhaps prevent or cure them, or at least diagnose them earlier and treat them better.

“Understanding the genetics of autoimmune disease should also help us stratify patients according to the likely severity of the course of their disease,” he said. “Is their rheumatoid arthritis likely to destroy their joints and need more aggressive treatment, or will milder medications be likely to control it? Learning how these genes work should also help us better target pathway in developing more effective treatment.

                  “To achieve this understanding of the genetics of autoimmune diseases, we need national and international cooperation to dissect these links at a fine level with well defined measures.“ 

UAB researchers are working with the HudsonAlpha Institute of Biotechnology in Huntsville on a project to build a detailed database of human genetic variation by sequencing the genomes of a large, diverse sample of people from around the world. The database will provide a baseline reference point for researchers studying how genes contribute to human diseases.

“Mcrobiome research is another area of inquiry that could tell us a lot about how autoimmune disease develops,” Bridges said. “In some conditions, the onset of symptoms has coincided with changes in the naturally occurring microorganisms in the body. Much as the human genome project was achieved though the combined efforts of many researchers, a survey of the human microbiome has been underway to catalog the thousands of microorganisms found on human skin and in the mouth, digestive tract and reproductive system. UAB researchers contributed to the work, and a preliminary report was recently published that should give us a starting point in looking at the links between the microbiome and autoimmune diseases.”

In addition to continuing research into the pervasive sharing of the genetic effect of human DNA in autoimmune diseases, Bridges anticipates more study investigating how the DNA of microorganisms within the body function to help to prevent or trigger autoimmune diseases.

“There’s some data suggesting that the bacteria involved in gum disease may be linked to a greater risk of rheumatoid arthritis. We plan to partner with the UAB School of Dentistry in research looking into how they might be related,” Bridges said.