Autoimmune Diseases Three Times More Likely in Families of Children with JRA
Are there common susceptibility genes that must be present for a variety of autoimmune diseases to occur? If so, what additional genes do they interact with to produce specific autoimmune disorders?
Those are among the questions being studied by Edward Giannini, MSc, DrPH; Susan Thompson, PhD; David Glass, MD; and colleagues in the Division of Rheumatology at Cincinnati Children's. The objective of a recent study was to determine if the prevalence of autoimmunity among relatives of patients with juvenile rheumatoid arthritis (JRA) is greater than that among relatives of healthy volunteer control subjects. The results would help to establish the genetic link among autoimmune diseases.
"Multiple genes must be present for autoimmune diseases to develop. These disorders all have complex genetic traits. It's likely that general autoimmune disease genes interact with those for specific diseases to produce disorders such as JRA or type 1 diabetes in children. We believe that these general and specific genes have varying amounts of influence in making you susceptible to autoimmune diseases," Dr. Giannini explains.
Diseases May Share Common Genes
For the study, researchers drew on Cincinnati Children's extensive registry of patients and families with JRA to identify 110 patients and their family members; an additional 23 families with sibling pairs with JRA also participated. In addition, 45 control volunteers were recruited. All participants provided family histories among first- and second-degree relatives for 14 autoimmune disorders, including JRA, rheumatoid arthritis, Hashimoto thyroiditis and multiple sclerosis.
| Rheumatology Physicians Achieve Top Honors |
Glass to Accept Distinguished Investigator Award
 David Glass, MD, director of the Division of Rheumatology, has won the Distinguished Investigator Award, presented by the American College of Rheumatology (ACR) to honor a senior scientist who has made significant contributions to the field of rheumatology. Glass was nominated by colleague Robert Colbert, MD, PhD, associate professor of Rheumatology, on behalf of the Executive Committee of the ACR's Pediatric Rheumatology Section. He wrote, "While serving as director of the Division of Rheumatology in Cincinnati, Dr. Glass' leadership locally and nationally has promoted the scientific development of pediatric rheumatology. In my opinion, he is the person most responsible for elevating our subspecialty." Glass is the first pediatric rheumatologist to win the Distinguished Investigator Award. He will receive the award in October, at the annual meeting of the ACR in Orlando. |
Giannini Receives National Arthritis Foundation Award
The Arthritis Foundation recently awarded the prestigious Virginia P. Engalitcheff Award for Impact on the Quality of Life to Edward Giannini, MSc, DrPH, professor of pediatrics in the Cincinnati Children's Division of Rheumatology. Dr. Giannini is the author of more than 190 medical studies and textbook chapters on pediatric rheumatology. In his 30-year career, he has helped tens of thousands of children around the world through his research into the treatments that work -- and those that don't -- in children with JRA. Thanks largely to his contributions, doctors can now recommend the drugs with the greatest chance of success. |
"We included only those autoimmune disorders that we were confident we could classify correctly," Dr. Giannini says. "Then we looked for an increased frequency of these diseases in family members."
What they found supported their theory. Parents, siblings, aunts and uncles of children with JRA were three times more likely than members of the control group to have an autoimmune disease themselves, with a significantly higher incidence among the women in the group. The most significant association was seen between JRA in children and Hashimoto's thyroiditis in their relatives.
"This suggests that two clinically different diseases may share common susceptibility genes, which may act as risk factors for autoimmunity," Dr. Giannini says.
As a result of these and other investigations, laboratory studies are ongoing in a large cohort of more than 700 patients and families. The studies are directed at finding these common susceptibility genes and are also studying their levels of expression. This effort involves a considerable number of the division's staff, including Michael Barnes, PhD; Robert Colbert, MD, PhD; Alexei Grom, MD; and Sherry Thornton, PhD.
Potential for Earlier Diagnosis
For relatives of patients with autoimmune diseases, these findings mean that once the relatives are identified as being at increased risk, physicians can increase their surveillance for symptoms that would indicate they are developing an autoimmune condition themselves. They may be able to recommend treatment to offset the disorder's onset, or to intervene early once the disorder first manifests itself.
Eventually, researchers believe these common susceptibility genes that raise an individual's risk for autoimmune disorders will be identified, opening new avenues for diagnosis and treatment. "In the future, it's likely that a diagnostic gene chip will be developed that, with a small blood draw, will test for expression of these autoimmune genes and confirm a diagnosis," Dr. Glass explains. "What's more, we also will be able to predict the likely response to treatment.
"We're taking advantage of the new knowledge of the genome to understand the molecular basis of autoimmune diseases, so that we can improve the quality of life and outcomes for children who suffer with them."
This study was published in Arthritis & Rheumatism (46[7]:1851-1856, 2002 July) and was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Schmidlapp Foundation, the Fifth Third Bank, The Arthritis Foundation (Ohio River Valley Chapter), Cincinnati Children's Research Foundation and The Val A. Browning Charitable Foundation.
