Research Finds Juvenile Arthritis Based in Innate Immune System

“Juvenile arthritis is often thought of as an autoimmune disease. That would mean a disease that emerges because the immune system gets mixed up in its ability to distinguish from itself what’s foreign, for example, a bacteria or virus,” he said.

“The trouble is, no one could ever figure out why so many areas of the genome that seemed to convey genetic risk for juvenile arthritis weren't located in genes that control that process,” said Jarvis. 

The new data suggests a more nuanced paradigm, involving human neutrophils, the white blood cells that fight infection and that are part of the innate immune system, which instantly responds to an injury or infection. 

Finding neutrophils play a key role in juvenile arthritis demonstrates that the disease involves the innate immune system, which operates almost instantly when someone experiences an injury or infection.

“It's the innate immune system that causes, for example, the redness and swelling that you get around a cut or a bruise,” said Jarvis, director of research in the Division of Allergy/Immunology and Rheumatology at the Women and Children’s Hospital of Buffalo. 

“Neutrophils are actually the most abundant cell in the inflamed joints of children with juvenile arthritis,” explained Jarvis, who also sees patients through UBMD Pediatrics. 

“People have assumed that because JIA is a chronic disease, that innate immunity must not be very important. We have shown that it is. Our new paper reinforces some of our previous findings showing genetic risk for JIA resides in neutrophils, some of the most important elements in the innate immune system.”

Jarvis is one of the few researchers who has been studying neutrophils’ role in JIA.

Jarvis’ research team sequenced ribonucleic acid (RNA) from the neutrophils of 16 children with a form of JIA. In addition, they looked at gene control switches in both neutrophils and CD4+T cells, which also fight infections, from healthy adults. 

“Different cell types have slightly different ‘control switches,’ located in and around the DNA, to regulate and coordinate the turning on and off of specific genes,” Jarvis said. “We show that there are important ‘control switches’ in neutrophils that lie right in the middle of regions where other investigators have identified genetic risk for this disease.”

These regions also happen to be strongly affected by epigenetic changes, DNA changes that don’t alter DNA sequencing, but are influenced by factors in the genomic environment and the individual’s environment, including lifestyle, behavior, exposure to pollutants and many other factors. 

“Our paper shows that genetic risk and epigenetic risk are closely linked in JIA, as most of the genetic risk occurs in regions of the genome where epigenetic influences are also operating,” said Jarvis.

Jarvis’ co-authors include: 

• Kaiyu Jiang, research scientist in the Department of Pediatrics
• Lisha Zhu, PhD, post-doctoral associate in the Department of Biochemistry
• Michael Buck, PhD, assistant professor of biochemistry
• Yanmin Chen, research technician
• Bradley Carrier, medical student
• Tao Liu, PhD, assistant professor of biochemistry 

The study was supported by grants from the National Institutes of Health and the Arthritis Foundation.