Gout is a form of inflammatory arthritis that can cause pain, swelling, and stiffness in the joints. It typically affects one joint at a time starting at the base of the big toe. According to the American College of Rheumatology, it impacts more than 3 million people in the United States.
Researchers have identified several factors that increase the risk of gout. But a new study led by the University of California San Diego School of Medicine identified a novel molecular pathway that may be key to gout’s tissue eroding effects.
The body makes uric acid when it breaks down purines. When uric acid levels are elevated, it causes hyperuricemia which causes uric acid to form in joints promoting inflammation.
However, hyperuricemia doesn’t always cause gout.
The researchers studied the case of a 22-year-old woman with an unusual case of gout. She had developed urate crystal deposits and had erosion in her joints, but she did not show high levels of urate in her blood.
Using a variety of sequencing and quantitative methods, the scientists were able to identify a molecular pathway that was disrupted in the women.
They found that numerous proteins were lower in her joint fluid as compared to her parents. One of these proteins was lubricin which tends to be low in people with gout and hyperuricemia.
Lubricin is involved in homeostasis or uric acid. It is responsible for inhibiting inflammation caused by the crystals, and it limits crystals from forming.
Another part of the study looked at mice engineered to not have lubricin and mice with lubricin. They found a key enzyme that produces uric acid in the mice that did not have lubricin.
This suggests that lubricin suppresses the secretion of urate and xanthine oxidase by activating white blood cells. It also blocks urate from crystalizing in the joint.
Dr. Puja Paul Khanna, an associate professor in the Department of Internal Medicine at the University of Michigan Medical School who was not involved in the study, believes the research establishes that lubricin could be a biomarker for gout.
“In the mouse models, they are seeing that even if you did not have a high level of uric acid, you are seeing damage because of those tiny little, you know, monosodium urate crystals happening already. That’s the pathway that we could block because we’ve already identified lubricin as the reason,” Khanna says.
“If the mice are deficient, meaning they lack lubricin, the crystals have a higher likelihood of depositing themselves and damaging that joint,” he goes on to say.
Senior editor of the study and professor at the University of California San Diego School of Medicine Robert Terkeltaub explains that gout risk may be influenced by gene variants individuals have for lubricin and molecules that control lubricin.
Dr. Theodore Fields, a rheumatologist at Weill Cornell Medicine and Hospital for Special Surgery in New York who was not involved in the study had this to say.
“It makes perfect sense that factors such as lubricin deficiency play a role in some patients because we continue to have major knowledge gaps about why some patients get gout and some don’t, even if both have the same level of serum urate,” he said.
More research is needed to determine whether lubricin could work as a novel therapeutic target for the prevention and treatment of gout.