New Research May Have Identified a Root Cause of Lupus

posted in Research Studies in Lupus on August 1, 2024 by

Gavin Abson

Updated July 11, 2024

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Lupus, a complex autoimmune disease, affects over a million people in the U.S. Researchers at Northwestern Medicine and Brigham and Women’s Hospital believe they have discovered a root cause of lupus. This breakthrough offers new hope for better treatments and possibly a cure for lupus.

Understanding the Root Cause of Lupus and Its Impact

Lupus, also known as systemic lupus erythematosus (SLE), is an autoimmune disease where the immune system attacks healthy cells. This can result in damage to multiple organs, including the heart, kidneys and brain. Common symptoms include extreme fatigue, joint pain, and skin rashes. In severe cases, lupus can lead to life-threatening complications.

The Role of T Cells and Interferon

Researchers have identified a fundamental imbalance in the types of T cells in lupus patients. T cells are white blood cells crucial for the immune response. The study found that lupus patients have too many T peripheral helper cells and too few regulatory T cells. This imbalance leads to the production of autoantibodies, which attack healthy cells.

Central to this imbalance is a protein called interferon. Lupus patients have excess amounts of type I interferon, which disrupts the immune system. High levels of type I interferon block the aryl hydrocarbon receptor (AHR), which regulates the body’s response to pollutants and bacteria. This blockage hinders the production of T cells that heal tissues and promotes T cells that produce autoantibodies.

Research Findings and Methodology

The study compared blood samples from 19 lupus patients with samples from healthy individuals. Researchers discovered that lupus patients have an imbalance in T cells linked to high levels of type I interferon. This imbalance could explain the root cause of lupus in most cases.

Dr. Deepak Rao, a rheumatologist at Brigham and Women’s Hospital, emphasized the significance of these findings. He stated, “What we found was this fundamental imbalance in the types of T cells that patients with lupus make.”

Implications for Treatment

Current lupus treatments often involve broad immunosuppression, which can also reduce the immune system’s ability to fight infections. However, the new findings suggest more targeted treatments could be developed. By addressing the specific T cell imbalance, new therapies may be more effective and have fewer side effects.

One promising treatment is anifrolumab, a drug that blocks interferon. The study showed that anifrolumab could prevent the T cell imbalance in lupus patients. Dr. Jaehyuk Choi, a dermatologist at Northwestern Medicine, noted, “We followed patients who received this as part of their clinical care and showed that in patients who got the drug, this cell imbalance was fixed or was on the way to getting fixed.”

Future Directions

While the findings are promising, further research is needed to confirm the results in larger patient groups. Dr. Jill Buyon, director of the Lupus Center at NYU Langone Health, cautioned, “Until they study 100 patients prospectively, how are we going to know?”

Researchers also explored using small molecules to activate the AHR. In blood samples from lupus patients, these molecules limited the accumulation of disease-promoting T cells. This approach could lead to new treatments that specifically target the underlying causes of lupus.

Challenges and Considerations

Developing new treatments involves challenges, particularly in ensuring they are safe and effective. Dr. Choi highlighted the difficulty of administering treatments without causing side effects. Activating AHR throughout the body could lead to unintended consequences.

Despite these challenges, the research represents a significant step forward in understanding lupus. The possibility of more effective treatments offers hope for lupus patients who have not responded to standard therapies.

Expert Opinions and Skepticism

While the research on the root cause of lupus is groundbreaking, some experts urge caution. Mara Lennard Richard, a scientific program officer for the Lupus Research Alliance, expressed optimism but also noted the complexity of lupus. She said, “It’s been very hard to find one singular root cause for the disease.”

The Lupus Research Alliance, which contributed grant funding to the study, remains hopeful about the potential impact of these findings. However, they emphasize the need for continued research to validate the results and explore new treatment avenues.

The Path Forward with Root Causes of Lupus

The research conducted by Northwestern Medicine and Brigham and Women’s Hospital has opened new possibilities for understanding and treating lupus. By identifying a potential root cause, scientists can develop targeted therapies that address the specific mechanisms driving the disease.

As research progresses, lupus patients may also benefit from more effective treatments with fewer side effects. This could improve the quality of life for those living with lupus and reduce the risk of severe complications.

The discovery of a potential root cause of lupus marks a significant milestone in lupus research. The findings provide a clearer understanding of the disease’s mechanisms and pave the way for more targeted treatments. While further research is necessary, the study offers hope for better management and possibly a cure for lupus.

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