Scientists Identify Key Causes of Lupus and Suggest New Treatment Approach

Key Causes of Lupus: Researchers from Northwestern Medicine and Brigham and Women’s Hospital have identified a molecular defect that drives the immune response in systemic lupus erythematosus (lupus). Their findings, published in Nature, suggest that reversing this defect could potentially reverse the disease.

Key Discoveries and Insights

Molecular Defect Identified: The study highlights two cellular defects that contribute to the pathological immune response in lupus. These defects lead to an imbalance in the immune system, promoting disease-causing immune cells.
Role of Aryl Hydrocarbon Receptor (AHR): Insufficient activation of the AHR pathway, which regulates cells’ response to environmental pollutants, bacteria, or metabolites, results in an overproduction of T peripheral helper cells. These cells promote the production of harmful autoantibodies.
Potential for Treatment: By reactivating the AHR pathway with small molecules or limiting excessive interferon in the blood, the researchers were able to reduce the number of disease-causing cells in lupus patients’ blood samples.

Implications for Lupus Treatment

Targeted Therapy: Current lupus treatments broadly suppress the immune system, leading to significant side effects. The new findings offer a potential for targeted therapies that can correct the immune imbalance without compromising the immune system’s ability to fight infections.
Reprogramming Disease-Causing Cells: The researchers demonstrated that activating AHR in lupus patients’ blood samples could reprogram the harmful T peripheral helper cells into Th22 cells, which may aid in healing the damage caused by lupus.

Key Causes of Lupus: Future Directions

Developing New Treatments: The team, led by Dr. Jaehyuk Choi and Dr. Deepak Rao, aims to develop novel treatments based on their findings. They are exploring safe and effective ways to deliver the AHR-activating molecules to patients.
Expanded Research: The study’s authors plan to continue their research, supported by numerous grants from the National Institutes of Health (NIH) and other organizations.

Contributors to the Study

Key Causes of Lupus: The research involved contributions from several scientists and institutions, including:

Northwestern Medicine: Dr. Jaehyuk Choi, Calvin Law, Arundhati Pillai, Brandon Hancock, and Dr. Judd Hultquist.
Brigham and Women’s Hospital: Dr. Deepak Rao, Vanessa Sue Wacleche, Dr. Ye Cao, Dr. John Sowerby, Dr. Alice Horisberger, Sabrina Bracero, Ifeoluwakiisi Adejoorin, Eilish Dillon, Dr. Daimon Simmons, Dr. Elena Massarotti, Dr. Karen Costenbader, Dr. Michael Brenner, and Dr. James Lederer.

The research was funded by grants from the NIH, Lupus Research Alliance, Burroughs Wellcome Fund, Bakewell Foundation, Leukemia and Lymphoma Society, and American Cancer Society.

Key Causes of Lupus: This breakthrough offers hope for more effective and less harmful treatments for the 1.5 million people in the U.S. affected by lupus, providing a new direction in the fight against this debilitating autoimmune disease.