Improved Understanding of Damaging Immune Response in Rheumatoid Arthritis

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

The findings, published in Science Immunology, were the result of a seven-year collaboration led by Monash University, involving Janssen Biotech, Inc., Janssen Cilag Pty Ltd., Janssen Research & Development, LLC and the Karolinska Institute, Sweden.

Certain immune system genes, called Human Leukocyte antigen (HLA)-DR4, cause an increased susceptibility to RA.  In this study, using mice genetically modified to express the human HLA-DR4 molecule, the team examined, at the molecular and cellular levels, how T cells recognise these HLA-DR4 molecules. The team also showed that highly similar T cell receptors, likely with similar recognition characteristics, are also present in “RA-susceptible” humans expressing these HLA molecules.

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

Reference
Lim JJ, Jones CM, Loh TJ, et al. The shared susceptibility epitope of HLA-DR4 binds citrullinated self-antigens and the TCR. Science Immunology. 2021;6(58). doi:10.1126/sciimmunol.abe0896

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