New biomarker for gout may monitor disease

Gout not properly treated can cause health damage even between acute attacks. Radboudumc and Université Paris Cité have found a new biomarker by which monosodium urate crystal-induced inflammation can be monitored very well. This can possibly reduce health damage over time.

Gout is a very painful joint inflammation, provoked by the crystallization of monosodium urate. The number of people with gout is increasing rapidly. Worldwide, more than 45 million people, mostly men, currently suffer from this rheumatic disease. The last 30 years, numbers have doubled. Between the acute, painful gout flares are quiet periods with, however, elevated concentrations of serum urate. With drugs such as allopurinol, the serum urate concentration can be reduced enough to dissolve the deposited crystals and subsequently to cure and prevent attacks. Much is still unclear about the exact disease process.

Four proteins

To gain a better understanding of the process of the disease, research groups of Leo Joosten (Radboudumc) and Pascal Richette (Universite Paris Cite, INSERM) analyzed in 71 patients exactly which inflammatory proteins are involved in the three different stages of gout: the acute flare-up, the quiescent intermediate period and the period in which serum urate levels are normalized by drugs. "Using proteomics techniques, we looked for about a hundred proteins that may be involved in inflammatory processes," said Brenda Kischkel, first author of the study published in Annals of the Rheumatic Diseases. "We saw four proteins play an important role in the acute phase of gout attacks. Of those four, the protein TNFSF14 appeared to play a central role. It may become a new, excellent biomarker for gout."

New biomarker

"Studies in mice showed that this TNFSF14 protein is produced locally in the joints by crystal formation itself," says co-first author Hang-Korng Ea. "Moreover, this protein appears to stimulate the production of other inflammatory factors, including several interleukins." The important role of TNFSF14 was also confirmed by looking at small changes in the gene for this protein in a large group of patients. Richette: "Those small genetic changes called SNPs can cause a protein to work just a bit better or worse. That was exactly what we saw. Some SNPs boost inflammation, while other SNPs dampen it. This shows again that TNFSF14 is a new biomarker for gout.”

Monitoring gout required

The discovery offers possibilities for developing antibodies to treat gout attacks. Joosten: "That is actually not a real option, because we already have good drugs doing that, such as colchicine, steroid and interleukin-1 blockers. A better option could be monitoring the disease through this protein. In addition, it can also be suitable for finding out quickly whether new drugs work or not. By monitoring the disease globally, much can be gained in terms of health and quality of life. Even if you do not have an acute attack, too high a concentration of serum urate in the blood causes continuous, low-grade inflammation. This increases the risk of cardiovascular disease and kidney damage. Plenty of reasons to take gout research and treatment seriously."

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Paper in in Annals of the Rheumatic Diseases: Systemic inflammatory cytokine profiles in patients with gout during flare, intercritical and treat-to-target phases: TNFSF14 as new biomarker - Hang-Korng Ea, Brenda Kischkel, Twinu Wilson Chirayath, Viola Klück, Caroline Aparicio, Hoang-Uyen Loeung, Philippe Manivet, Tim Jansen, Mylène Zarka, Frédéric Lioté, Augustin Latourte, Thomas Bardin, Alan Gauffenic, Eric Vicaut, Tania Octavia Crișan, Mihai G Netea, Pascal Richette, Leo Joosten

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