Nearly one in three children with the most common forms of juvenile idiopathic arthritis develop a visual disorder called uveitis. To better understand the cause of uveitis, researchers in a recent study have identified a genetic sequence that could help advance scientific progress toward preventing and treating the disorder.
According to the study, the genetic sequence of the HLA-DRβ1 gene could help explain the increased incidence of the sight-limiting disorder seen in girls with juvenile idiopathic arthritis.
The finding was reported in the study, “An amino acid motif in HLA-DRβ1 distinguishes patients with uveitis in juvenile idiopathic arthritis,” published in the journal Arthritis & Rheumatology.
Uveitis is the inflammation of the pigmented layer of the eye. Left untreated, it can compromise a child’s vision and severely affect their quality of life.
Several genes have been associated with both juvenile arthritis and uveitis, but they only explain about 20 percent of cases. To better understand the underlying genetics that link these two disorders, the research team conducted a genome-wide association study.
The team analyzed DNA samples from 522 patients ages 12 to 18 who were diagnosed with juvenile idiopathic arthritis. Of those, 192 had uveitis.
They found that patients who had a serine amino acid in position 11 of the HLA-DRβ1 gene had a 2.6 times greater probability of developing uveitis. Interestingly, the serine-11 was only found to be correlated with uveitis in female patients. This suggests that the newly identified genetic sequence is a specific contributor to uveitis in girls with juvenile arthritis.
HLA-DRβ1 is an essential component of the immune system that regulates immune responses involved in both arthritis and uveitis. The team found that serine-11 was perfectly associated with other HLA-DRβ1 amino acids previously linked to both juvenile idiopathic arthritis and uveitis. The presence of serine-11 may change the way HLA-DRβ1 functions, promoting the susceptibility to uveitis.
The researchers believe that these findings represent a key step in understanding the “biologically shared and distinct features” of juvenile arthritis with and without uveitis. Further studies are still needed to identify additional genetic biomarkers that contribute to disease risk.
“By pinpointing and understanding the molecular mechanisms of uveitis, we can identify biomarkers that stratify patients for disease risk, catalyze future lines of research in precision medicine, and advance towards treating and preventing sight-threatening complications of uveitis in children with [juvenile idiopathic arthritis],” the researchers stated.