A recent study by Johns Hopkins Medicine has revealed new insights into why symptoms and severity of lupus can vary among individuals with the autoimmune condition, which impacts as many as 1.5 million Americans. This discovery is a significant step in understanding the biological mechanisms behind lupus and could potentially change how healthcare providers approach treatment for patients with the condition.m describes this as a significant advancement in comprehending the biological processes that underlie lupus. It could potentially result in a shift in how medical professionals approach the treatment of patients with this condition.
The comprehensive report, which was released in Cell Reports Medicine on May 13, indicates that particular combinations and increased levels of immune system proteins, known as interferons, are linked to specific lupus symptoms such as skin rashes, kidney inflammation, and joint pain. In lupus, interferons become overactive, leading to widespread inflammation and damage, despite their normal role in fighting infection or disease. The study also reveals that other common l
Increased levels of interferon cannot explain symptoms related to lupus.
According to rheumatologist Felipe Andrade, M.D., Ph.D., who is the corresponding author and an associate professor of medicine at the Johns Hopkins University School of Medicine, there has been a growing understanding of the role of interferons in lupus. This research originated from the observation that certain treatments for lupus were not effective for some patients. Dr. Andrade explains, “We have seen cases where patients did not improve as expected, which led us to question the possible involvement of specific groups of interferons.”
Some treatments for lupus aim to suppress particular groups of interferons., also known as interferon I, was the focus of clinical trials. Despite high levels of interferon I being detected in some patients through genetic testing before treatment, not all patients showed improvement. This was referred to as a high interferon signature. The research team suspected that interferon II and interferon III might be responsible for the lack of response to treatment in these cases.
In order to investigate this further, the team studied the potential impact of different combinations of interferon I, II, and III, as well as their overactivity, on individuals with lupus. They collected 341 samples from 191 participants to assess the activity of the three interferon groups .
Researchers used human cell lines that were modified to detect and respond to specific types of interferons in order to study the samples. This led to the identification of four categories of participants: those with only increased interferon I, those with increased interferons I, II, and III, those with increased interferons II and III, and those with normal levels of interferon.
Using this information, researchers were able to draw connections between the combinations of interferons and symptoms of lupus. They found that elevated interferon I was mainly linked to symptoms of lupus such as skin rashes.Elevated levels of interferon I, II, and III in participants with lupus were linked to more severe symptoms, including skin issues like rashes and sores, as well as significant damage to organ systems such as the kidneys. However, not all symptoms of lupus were connected to increased interferon levels. For example, blood clot formation and low platelet counts were not associated with higher levels of interferon. This suggests that both interferon-dependent and other biological mechanisms play a role in the development of lupus. Additionally, the study found that genetic testing may also be useful in understanding the disease.The identification of genes linked to these groups of interferons, known as the interferon signature, did not consistently indicate increased levels of interferons. The researchers plan to explore this further in future studies.
“Our study revealed that these groups of interferons do not act in isolation; they collaborate in lupus and can result in different disease presentations for patients,” explained rheumatologist Eduardo Gómez-Bañuelos, M.D., Ph.D., who is an assistant professor of medicine at the Johns Hopkins University School of Medicine and the lead author of the study. Examining a patient’s elevated combinations of interferons can lead to a better understanding.The determination of how patients with lupus may respond to treatments and the ability to categorize them into clinical subtypes of the disease is important, according to Gómez-Bañuelos. Additional contributors to this study are Daniel Goldman, Victoria Andrade, Erika Darrah, and Michelle Petri, all associated with the Johns Hopkins University School of Medicine. Darrah is also now associated with AstraZeneca. Funding for this research project comes from grants from the National Institutes of Health, including R21 AI147598, R21 AI169851, R21 AI176766, and R01 AR069572, as well as from the Jerome L. Greene Foundation. Journal Reference: [].In a 2024 study published in Cell Reports Medicine, researchers Eduardo Gómez-Bañuelos, Daniel W. Goldman, Victoria Andrade, Erika Darrah, Michelle Petri, and Felipe Andrade discovered a link between interferons and the interferon signature that explains clinical and transcriptional subsets in systemic lupus erythematosus (SLE).
