Molecular gatekeeper of arthritis identified
Washington, Sept 9 : Scientists have discovered that elimination of a molecular gatekeeper leads to the development of arthritis in mice.
The newly discovered gatekeeper is a protein that determines the fate - survival or death - of damaging cells that mistakenly attack the body''s own tissues and lead to autoimmune disorders such as arthritis.
Better understanding how arthritis develops will offer scientists an opportunity to explore new types of treatments for patients whose arthritis has not been effectively treated with current therapies.
"This finding is an encouraging step forward for researchers, clinicians and arthritis sufferers, many of whom fail available therapies," said lead researcher Frances Lund, professor of Medicine in the Division of Allergy/Immunology and Rheumatology at the University of Rochester Medical Center.
"An added bonus is that this finding may help in the search for new treatments for other autoimmune disorders, such as lupus."
The protein at the center of the new finding, known as Gaq (G alpha q), is part of a larger signaling pathway that Lund and collaborators from across the United States and China investigated in mice.
Gaq regulates B cells, one type of immune cell that the body maintains to fight off invaders like bacteria, viruses and parasites. While most B cells help defend the body, some B cells are autoreactive - they turn against the body''s own tissues.
In mice, Gaq normally stops autoreactive B cells from building up in tissues by suppressing the pro-survival signaling pathway uncovered by Lund''s team. When Gaq is eliminated, autoreactive B cells are able to pass through internal ''checkpoints'' that typically get rid of these harmful cells, creating a buildup of the cells that contributes to the development of autoimmune disease.
Several new studies expanding on the current finding are in the works, including testing whether drug compounds that alter the expression or activity of Gaq in mice can slow the development of autoimmunity.
Beyond preclinical testing in mice, researchers also hope to start screening Gaq levels in patients to learn more about how the protein works in humans.
According to Lund, "There is a subset of cardiac patients who, due to an inherited genetic mutation, have increased levels of Gaq. We are now looking to see if some arthritis patients have mutations that favor decreased levels of Gaq. If we find these patients, someday we may be able to design targeted, personalized therapy for this subpopulation of arthritis sufferers."
The study has been published in The Journal of Experimental Medicine. (ANI)