Many Americans consider gout as a disease from a bygone era, akin to rickets or scurvy. The condition commonly afflicted the wealthy and royal, including American historical figures akin to Benjamin Franklin and Thomas Jefferson.
Gout is indeed considered one of the earliest known diseases, first identified by the traditional Egyptians around 2640 BC. However the disease is more prevalent now than ever, affecting greater than 10 million people in america or roughly 5 percent of the adult population.
Gout is essentially the most common type of inflammatory arthritis, through which urate (a byproduct of purine-rich foods like meat and alcohol) builds up within the body and forms needle-shaped crystals in and across the joints, normally starting within the foot. The crystal deposits result in flares of severe pain, joint swelling and tenderness, and may progress to chronic joint damage that limits patients’ movement and quality of life.
Excess urate circulating within the blood (often known as hyperuricemia) has long been considered the key reason behind gout, but counterintuitively, most individuals with high urate levels don’t actually develop the disease. In actual fact, asymptomatic hyperuricemia is roughly 4 times more prevalent than gout. Gout patients also show mysteriously higher levels of urate of their joint fluid in comparison with their blood. Thus hyperuricemia must not be the one thing stimulating urate crystal deposition within the joints. So what else may very well be causing the disease?
In a recent study published online on December 1, 2022 in Arthritis & Rheumatology, a global research team led by University of California San Diego School of Medicine identified a novel molecular pathway that causes gout and its progression to joint tissue erosion. The findings position lubricin, a protein present in joint fluid, as a novel therapeutic goal for each the prevention and treatment of the disease.
The scientists were all in favour of exploring the genetic aspects that lead to not high levels of circulating urate, but specifically to urate production and crystal deposition inside joints. To do that, they studied a rare case of gout through which the patient had developed urate crystal deposits and erosion in her joints but didn’t show high levels of urate in her blood.
This naturally occurring and very unusual disorder provided a novel opportunity to take a look at gouty arthritis through a unique lens, and understand what molecular processes contribute to the disease independent of hyperuricemia.”
Robert Terkeltaub, MD, senior creator, professor at UC San Diego School of Medicine and section chief of rheumatology on the Veterans Affairs San Diego Healthcare System
Using whole genome sequencing, RNA-sequencing and quantitative proteomic methods, the researchers were in a position to discover a significant molecular pathway that was disrupted within the patient, centering on a major reduction in lubricin. The mucinous protein provides essential lubrication and protection to joint tissues, and regulates the function of a particular variety of white blood cell that promotes inflammation within the joint.
Additional experiments confirmed that under healthy conditions, lubricin suppresses the secretion of urate and xanthine oxidase (an enzyme that produces urate) by activated white blood cells, and in addition blocks urate from crystallizing within the joint. The researchers then assessed several patients with the common type of gout and confirmed that they too had markedly decreased levels of lubricin.
The authors suggest that whether or not a hyperacemia patient goes on to develop gout may thus be influenced by which gene variants they’ve for lubricin and other molecules that control its production or degradation within the joint.
“Our findings show that lubricin could also be a recent biomarker for tracing patients’ risk of developing gout, and that recent drugs to keep up and increase lubricin could limit the incidence and progression of gouty arthritis,” said Terkeltaub.
Source:
University of California San Diego