How did my child get arthritis? Pediatric rheumatologists get this question all too often, and researchers still have more questions than answers.But they have made some progress in recent years, particularly in understanding the relationship between genes and environmental factors that are believed to play a role in autoimmune diseases like juvenile arthritis (JA).
Autoimmune diseases develop when something goes awry in the body’s natural immune system. Instead of protecting the body against things like flu viruses, the immune system attacks its own cells by mistake. In JA, this can result in painful inflammation, fever and other symptoms. But JA is only one of many autoimmune diseases; others include multiple sclerosis, Type 1 diabetes and some thyroid disorders.
Genetics plays a large role. While some diseases like cystic fibrosis or sickle cell anemia are associated with a single gene, JA is believed to be associated with a number of genes. To date, more than a dozen genes – out of an estimated 20,000 to 40,000 in the entire human genome (the genetic information in a person) – have been identified as strongly associated with juvenile idiopathic arthritis (JIA) specifically. In addition, several hundred genes are considered to be candidate genes, which may play a role by expressing themselves differently in patients with the common form of JIA.
Autoimmune Disease: Trunk and Branches
One way to understand the relationship between autoimmunity and specific diagnoses is to picture a tree trunk and its branches. The trunk represents autoimmunity – that is, those genes that boost your child’s vulnerability to developing any one of a number of autoimmune diseases. Branching out are a number of other genes and genetic markers that contribute to specific diseases, such as ankylosing spondylitis, systemic lupus erythematosus (SLE) or Type 1 diabetes.
Researchers interested in autoimmunity are looking into the HLA (human leukocyte antigen) complex to learn more about what may cause JIA. This cluster of genes, which reside on chromosome 6, is believed to play a significant role in fighting infection, as well as in the development of autoimmunity. In addition to the genes themselves, there are also related proteins that help the body’s immune system distinguish between its own cells and external invaders such as viruses.
We’re still in the early days of understanding what genetic markers may mean for our health, but researchers are starting to associate certain genes on the HLA complex with an increased risk of specific diagnoses. Testing positive for HLA-B27 is associated with a higher risk of developing one of the spondyloarthropathies. Other genes, such as HLA-DR1 and HLA-DR4, appear to be linked with children who have rheumatoid factor-positive polyarthritis.
HLA isn’t the only autoimmune region under the genetic microscope. In recent years, researchers have turned their sights on the PTPN22 variation, located on another chromosome, which they believe is associated with adult rheumatoid arthritis, juvenile rheumatoid arthritis, lupus and autoimmune thyroid disease.
So what does this new knowledge mean for you? Important genetic tests are being developed now, but their results may still not tell us what we need to know. Insightful in some cases, they may only provide a piece of the puzzle. Take the HLA-B27 test: The overwhelming majority of those diagnosed with ankylosing spondylitis, an arthritis that primarily affects the spine, will test positive for HLA-B27, particularly if they are Caucasian.
But individuals can carry HLA-B27 without developing any related arthritis of the spine.
By the same token, genes aren’t singularly bad. For every gene or genetic marker, such as a protein, that might nudge your child a little closer to developing an autoimmune condition, there are believed to be another set of genetic components that step in to slow or halt the process.
Furthermore, genes are likely only part of a two-step process. Environmental triggers are also believed to play a role. Your child may have a genetic profile that boosts her risk of developing arthritis, but having a particular genetic makeup, when coupled with certain outside influences, may tip the balance. What these environmental factors are is still being studied.
Applying Genetic Advances
By identifying and better understanding the roles of specific genes and related markers, researchers will start applying that knowledge in a number of ways. They may be able to more quickly isolate your child’s type of arthritis, which will help dictate treatment choices. At the same time, they may pick up genetic clues that help them predict the long-term course of her disease. Medication treatment also will one day benefit, thanks to an exciting technique called gene expression profiling, in which researchers can study genes that are turned on and turned off.
Unlike clinical trials, which essentially use a trial-and-error approach to determine how and when drugs work best, genetic expression profiling could one day help your child’s doctor better tailor the medication regimen to her genetic strain of disease. Less time wasted in trying medications will reduce both cost and frustration.
Most importantly, it will cut short the time required to get your child’s inflammation under control. Hopefully, the result will be less daily discomfort and the derailing of some of the longer-term effects of the disease.