New Research: A Root Cause of Lupus? [Reported July 2024]

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

Gavin Abson

Updated March 1, 2025

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New research claimed they discovered a root cause of lupus. Researchers at Northwestern Medicine and Brigham and Women’s Hospital reported this in July 2024. However, is it really a root cause of lupus? This article discusses the research more closely.

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NOTE: Johns Hopkins University Press, publisher of The Lupus Encyclopedia, is a nonprofit publisher. If you purchase anything from JHUP, you support projects like Project MUSE.

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This blog post article was edited and contributed to by Donald Thomas, MD; author of “The Lupus Encyclopedia.” Parts of this blog post come from “The Lupus Encyclopedia: A Comprehensive Guide for Patients and Health Care Providers, edition 2“

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Understanding the Root Cause of Lupus and Its Impact

Systemic lupus erythematosus (SLE), is an autoimmune disease where the immune system attacks healthy cells. This can damage 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.

SLE is a polygenetic disease. Around 200 genes have been discovered (as of March 2025) that increase the risk for SLE. However, most people with these genes never develop SLE. Other internal factors (like female hormones and low vitamin D levels) and external factors (like cigarette smoke, ultraviolet light, etc) interact with these genes, leading to excessive immune system activation.

Identifying the root causes of SLE can help us someday find better therapies and, hopefully, a cure for lupus.

The Role of T Cells and Interferon

Researchers have identified an imbalance in the types of T cells in lupus patients. T cells are white blood cells of the immune system. The study found that lupus patients have too many T helper cells and too few regulatory T cells. This imbalance leads to the production of autoantibodies by B cells (another type of white blood cell), which attack healthy cells and tissues.

Central to this imbalance is a protein called interferon. Lupus patients have excess type I interferon. Type I interferon helps fight viral infections. However, lupus patients have excess amounts of interferon. These high amounts of type I interferon tell white blood cells to be overactive and attack healthy body parts. Anifrolumab (Saphnelo) is a biologic that interferes with type I interferon activity and is the reason it helps many SLE patients.

Type I interferon blocks the aryl hydrocarbon receptor (AHR), which regulates the body’s response to invaders like bacteria. This blockage promotes T cells that stimulate B cells to produce autoantibodies (the antibodies that attack a lupus patient’s body).

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 unhealthy imbalance of T cells, and this is linked to high levels of type I interferon. The researchers stated that this imbalance could be a root cause of lupus.

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.”

Dr. Thomas Discusses the Research in This Video by Lupus LA

Although the title states “omega-3,” Dr. Thomas first discusses the results of this study and how he interprets it. He then presents some data on the usefulness of omega-3 fatty acids in SLE.

Implications for Treatment

Many immunosuppressants used to treat lupus involve broad immunosuppression, which can also reduce the immune system’s ability to fight infections. However, the new findings suggest more targeted treatments (like Saphnelo and Benlysta) could be developed. By targeting this specific T cell imbalance, new therapies may be more effective and have fewer side effects. However, this needs to be proven.

One promising treatment is anifrolumab (Saphnelo), which blocks interferon. The study showed that anifrolumab could prevent 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 the use of small molecules to activate AHR. In blood samples from lupus patients, these molecules limited the accumulation of disease-promoting T cells. This approach could lead to new treatments for 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.

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, “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, hopefully, effective treatments with fewer side effects will be discovered.

My thoughts (Don Thomas, MD) on this research is that it is important. I would not go so far as to say it is a “root cause of lupus.” It is too early to say this. It is more likely one of many immune system abnormalities that exist in people with lupus. This research gives us a clearer understanding of the disease’s mechanisms and paves the way for more targeted and better lupus treatments.

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For more in-depth information on New Research: A Root Cause of Lupus? [Reported July 2024]:

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