Researchers identify molecular gatekeeper of arthritis

The elimination of a key protein – referred to as a “molecular gatekeeper” – leads to the development of arthritis in mice, according to a study published in the Journal of Experimental Medicine.

The protein, researchers noted, determines the fate of damaging cells that mistakenly attack the body’s own tissues and lead to autoimmune disorders such as rheumatoid arthritis. The finding could help researchers explore new types of treatments for patients whose arthritis has not been effectively treated by other means.

“This finding is an encouraging step forward for researchers, clinicians and arthritis sufferers, many of whom fail available therapies,” stated lead researcher Frances Lund, PhD, in a press release. “An added bonus is that this finding may help in the search for new treatments for other autoimmune disorders, such as lupus.”

The importance of Gáq

The subject of the new finding is a protein known as Gáq (G alpha q), and it serves as part of a larger signaling pathway that Lund’s team investigated in mice. Gáq regulates B cells – an immune cell type that helps the body fight off bacteria, viruses and parasites. Some B cells are known to be autoreactive, meaning they can attack the body’s own tissues.

The researchers noted that Gáq normally stops autoreactive B cells from building up in mice by suppressing the pro-survival signaling pathway the team uncovered. When Gáq is eliminated, autoreactive B cells are able to pass through internal “checkpoints” where they normally get held up at – creating a buildup of the cells and contributing to the development of autoimmune disease.

Potential uses down the line

Several new studies expanding on the current finding are currently being performed – including testing to determine whether drug compounds that alter the expression or activity of Gáq in mice can slow the development of autoimmunity. Researchers are also hoping to start screening Gáq levels in patients to learn more about how the protein works in humans.

“We are now looking to see if some arthritis patients have mutations that favor decreased levels of Gáq,” Lund stated in the release. “If we find these patients, someday we may be able to design targeted, personalized therapy for this subpopulation of arthritis sufferers.”

“Our goal is to move the knowledge we’ve gained from basic research to meaningful results that will ultimately help patients, and our main finding … puts us in a very strong position to do that,” she added in the statement.

Reference:
Misra RS, Shi G, Moreno-Garcia ME, et al. Gáq-containing G proteins regulate B cell selection and survival and are required to prevent B cell–dependent autoimmunity. JEM. 207(8):1775. doi: 10.1084/jem.20092735

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