Scientists uncovered the molecular mechanism for the greatest lupus genetic risk factor

The discovery could be a route to novel treatments for autoimmune diseases.

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Lupus is a disease that occurs when your body’s immune system attacks your tissues and organs. Among its four types, Systemic lupus erythematosus is common that affects millions of individuals worldwide.

The greatest risk factor for the disorder, which involves inflammation in many vital organs and can cause severe disability and death, is a genetic variant known as HLA-DRB1*03:01.

A recent study by scientists from Michigan Medicine uncovered the molecular mechanism that drives the disease-causing effects of the most common genetic risk factor for lupus. Scientists found that a protein coded by that HLA variant triggers a cascade of molecular and cellular effects that can cause the inflammatory symptoms seen in lupus patients.

Joseph Holoshitz, M.D., senior author of the paper and professor of internal medicine and rheumatology at the University of Michigan Medical School, said, “For the first time, we have found the enigmatic mechanism that genetically predisposes people to the worst effects of the most typical form of lupus. The findings could potentially facilitate the discovery of safe, simple, and effective treatments for SLE by targeting this new pathway.”

A series of events that show how the abnormalities that can cause lupus to grow, from the first effect of the risk gene to signaling, all the way to immunological abnormalities and clinical signs of lupus, have been discovered in cell culture and animal models of the disease.

Bruna Miglioranza Scavuzzi, Ph.D., first author of the paper and a postdoctoral research fellow in the Division of Rheumatology at the University of Michigan Medical School, said“Human trials in RA with those compounds are being carried out, and I hope that our novel findings will lead to similar efforts to ease the burden of millions of lupus patients as well.”

Journal Reference:

  1. Miglioranza Scavuzzi, B., van Drongelen, V., Kaur, B. et al. The lupus susceptibility allele DRB1*03:01 encodes a disease-driving epitope. Commun Biol 5, 751 (2022). DOI: 10.1038/s42003-022-03717-x