New understanding of the deleterious immune response in rheumatoid arthritis

Researchers at Monash University’s Biomedicine Discovery Institute have made a breakthrough in understanding the role of high-risk immune genes associated with the development of rheumatoid arthritis (RA). Photo credit: Erica Tandori

Researchers at Monash University’s Biomedicine Discovery Institute have made a breakthrough in understanding the role of high-risk immune genes associated with the development of rheumatoid arthritis (RA).

The results, published in Science Immunology, are the result of a seven-year collaboration led by Monash University, involving Janssen Research and Development, USA, and the Karolinska Institute, Sweden.

Certain immune system genes called human leukocyte antigen (HLA) -DR4 make you more susceptible to RA. In this study, using mice genetically engineered to express the human HLA-DR4 molecule, the team examined at the molecular and cellular levels how T cells recognize these HLA-DR4 molecules. The team also showed that very similar T-cell receptors, likely with similar recognition properties, are also present in “RA-sensitive” people who express these HLA molecules.

“This suggests that there may be an immune signature of RA development that offers a potential path for diagnostic development or a window of opportunity for therapeutic development,” says Dr. Hugh Reid, who co-directed the study with Professor Jamie Rossjohn and Professor Nicole La Gruta at Monash University.

With the help of the Australian synchrotron, the researchers were able to determine the structure of the molecular complexes that form during the interaction between T-cell receptors and modified joint proteins that are bound to HLA-DR4. With this information, they were able to figure out what was important for this harmful T cell response.

“This research is a great example of how collaboration between key academic and industrial partners can lead to breakthroughs in basic research, which in turn provide opportunities for the development of better therapeutics for common diseases,” said Dr. Reid.

Rheumatoid arthritis is an autoimmune disease that affects about one percent of the world’s population. It is characterized by swollen, painful, stiff joints and, as a result, restricted mobility in those affected. By studying how T cells “sensitively” recognize altered joint proteins in complexes with HLA molecules, Monash scientists expanded our understanding of how these HLA molecules can predispose individuals to disease development. The knowledge gained can make a significant contribution to achieving the long-term goal of producing personalized drugs and / or preclinical interventions for the treatment of RA.

The immune receptor protein could be key in treating autoimmune diseases

More information:
JJ Lim el al., “The common susceptibility epitope of HLA-DR4 binds citrullinated self-antigens and the TCR”, Science Immunology (2021). immunology.sciencemag.org/look … 6 / sciimmunol.abe0896 Provided by Monash University

Quote: New Understanding of the Harmful Immune Response in Rheumatoid Arthritis (2021, April 16), accessed April 16, 2021 from https://medicalxpress.com/news/2021-04-deleterious-immune-response-rheumatoid-arthritis.html

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