Such clear biological differences are much less evident between categories of juvenile idiopathic arthritis (JIA) as currently defined. For example, oligoarticular and seronegative polyarticular disease are more similar than different, while so-called “enthesitis-related arthritis” excludes another enthesitis-related disease, psoriatic JIA.
Dr. Nigrovic highlighted a recent study that showed HLA associations for subtypes of JIA often overlap those in adult arthritis. Hinks, Bowes and colleagues studied 5,000 JIA patients and 14,000 healthy controls, finding that HLA associations for most subgroups of JIA corresponded to those for clinically related forms of arthritis in adults, strongly suggesting pathophysiologic continuity.8 For example, HLA associations for seropositive JIA are identical down to specific amino acids in the HLA binding pocket with those in seropositive rheumatoid arthritis (RA). “So there is in fact substantial overlap between juvenile and adult arthritis,” he said.
“This doesn’t mean children should be lumped with adults for all purposes,” he noted. Children will exhibit some differences, such as in drug clearance, toxicity and the effects of disease and treatment on growth. “But it’s important to keep your thinking clear on this topic. Don’t make the mistake of considering these forms of arthritis different simply because we sometimes need to treat children differently. It’s important to keep questions of etiology apart from those regarding the practicalities of treatment.”
As an analogy, Dr. Nigrovic noted that physicians don’t classify pneumonias as juvenile and adult, but rather by pathogenic agent, recognizing at the same time that the organisms that cause pneumonia can vary widely with age and risk factors.
Juvenile arthritis is different from adult disease in some ways, he said. In particular, arthritis in children is most common between the ages of one and four. These young children often develop disease in only a few joints and are prone to chronic anterior uveitis, a phenotype essentially never seen in adult-onset arthritis. This form of early-onset arthritis may be a distinct disease. However, because it still shares HLA associations with adult seronegative arthritis, “it’s also possible it’s the same disease but arising in a different milieu,” said Dr. Nigrovic. “We can’t really choose definitively between these two hypotheses at this point.”
GWAS data used to identify regions of DNA linked to human disease risk are revealing more about mechanisms involved in juvenile rheumatic diseases even beyond the HLA region, he said.
“These data are important for understanding mechanisms. Each hit corresponds to a pathogenic pathway implicated by human genetics in disease biology.” Importantly, most GWAS hits don’t reflect coding regions, but rather alter segments of DNA that regulate gene expression via binding of regulatory proteins such as transcription factors.
