In a new study published in Cell Reports Medicine, researchers from Johns Hopkins Medicine have made significant progress in understanding the reasons why lupus symptoms and severity vary among individuals with the autoimmune condition. Lupus affects approximately 1.5 million Americans, and the insights gained from this research could potentially lead to changes in how clinicians approach the treatment of patients with lupus. The study identifies specific combinations and elevated levels of immune system proteins called interferons as being associated with certain lupus symptoms, such as skin rashes, kidney inflammation, and joint pain. Interferons, which normally help to fight infection or disease, are overactive in lupus, leading to widespread inflammation and damage. However, the study also reveals that other common lupus-related symptoms cannot be explained by increased interferon levels.
Lead author Dr. Felipe Andrade, an associate professor of medicine at Johns Hopkins University School of Medicine and a rheumatologist, explains that the research was initiated to address the ineffectiveness of certain lupus treatments for some patients. The team observed cases where patients did not improve despite having high levels of interferon I, the target of some lupus treatments, before treatment. This led them to consider the role of interferon II and interferon III in these poor treatment responses. By examining how different combinations of interferon groups are present in individuals with lupus, the researchers were able to classify participants into four categories based on their interferon activity levels. These categories were linked to specific lupus symptoms, with the most severe presentations of the disease associated with elevated levels of multiple interferon groups.
The study found that not all lupus symptoms were associated with elevated interferon levels, suggesting that both interferon-dependent and other biological mechanisms contribute to the complexity of the disease. Certain symptoms, such as blood clot formation and low platelet counts, did not show an association with increased levels of interferon groups I, II, or III. The researchers emphasize that understanding the different combinations of elevated interferons in lupus patients can provide valuable information on how they may respond to treatments, allowing clinicians to categorize them into clinical subtypes of the disease. This approach could potentially lead to more personalized and effective treatment strategies for lupus patients.
The team used human cell lines engineered to respond to specific interferon groups to analyze samples from 191 participants and determine the activity of interferon I, II, and III. By studying these interferon combinations and their impact on lupus symptoms, the researchers were able to identify correlations between elevated interferons and certain manifestations of the disease, such as skin-related symptoms and organ damage. Despite the complexity of lupus, the study sheds light on the interconnected role of different interferon groups in shaping the clinical presentation of the disease and highlights the importance of considering these factors in treatment decisions.
Future research will focus on investigating the genetic testing of genes associated with interferon groups and the interferon signature, as well as further exploring the mechanisms behind these findings. The team plans to expand on their current understanding of how interferon groups interact in lupus and how they contribute to the variability of symptoms seen in patients. By delving deeper into these biological mechanisms, researchers aim to improve the precision and efficacy of treatments for individuals with lupus. The study was supported by grants from the National Institutes of Health and the Jerome L. Greene Foundation, demonstrating the importance of continued funding for lupus research to advance our understanding of this complex autoimmune condition.