May 22, 2019
Lupus is heterogeneous, meaning that symptoms are many and vary widely from patient to patient — one person may develop a rash, while another may have high blood pressure, joint pain, and anemia. About two thirds of adults with lupus have above-normal levels of immune system molecules called type I interferons that may drive the disease’s symptoms—but one third do not. About half of adults with lupus develop lupus nephritis, and nearly one third of patients with lupus nephritis develop end stage renal disease.
Lupus Research Alliance-funded scientist Dr. Virginia Pascual, Director of the Gale and Ira Drukier Institute for Children’s Health at Weill Cornell Medicine pioneered the analysis of the disease’s diversity.
Scientists need to account for lupus’ heterogeneity to improve the success rate of clinical trials in lupus and to develop more effective treatments that target the underlying disease pathways in each patient. In 2008, Dr. Pascual and her colleagues set the stage for understanding the diversity of the disease by introducing a new approach for investigating how the immune system works in patients with lupus that involved analyzing the activity of different genes . Funding for the study came from a 2005 Lupus Research Alliance Target Identification in Lupus grant.
Dr. Pascual and her team took the results further in a groundbreaking 2016 study when they found which genes were active in blood samples from 158 children with lupus . The researchers determined that they could separate the patients into seven groups, which might eventually enable scientists to tailor treatments for each group. Based on the novelty and significance of these findings, Dr. Pascual received the 2017 Lupus Insight Prize from the LRA that will allow her to delve deeper into lupus heterogeneity.
The Accelerating Medicines Partnership (AMP) RA/SLE, a collaboration between the National Institutes of Health, industry and non-profit organizations, including the LRA, is further analyzing heterogeneity by measuring how genes behave in cells from patients with lupus nephritis. A new study supported by the AMP used this approach to predict which patients with kidney inflammation would need more intensive treatment .
Lupus’ heterogeneity means that certain treatments may only work for particular patients—one treatment is unlikely to be effective for such a variety of symptoms and causes. Knowing more about, the disease’s diversity will allow researchers to design new drugs that target specific groups of patients.
The Accelerating Medicines Partnership (AMP) Rheumatoid Arthritis/Lupus is addressing heterogeneity further by measuring, using cutting-edge technologies, how the immune system behaves in patients with lupus nephritis. AMP is a collaboration between the National Institutes of Health (NIH), Foundation for the NIH (FNIH), six pharmaceutical companies, and several non-profit organizations, including the LRA. The AMP Lupus program is collecting kidney biopsies, blood, and urine samples from nearly 200 people with lupus nephritis (kidney inflammation) to understand the disease on a deep molecular level. This will help to 1) match changes in the cells and molecules of the kidneys, blood and urine with how the patient responds to standard of care and 2) identify lupus-causing pathways that could provide novel targets for drug development. A new study from the AMP Lupus program was able to predict which patients with kidney inflammation would need more intensive treatment .
Lupus’ heterogeneity means that certain treatments may only work for some patients—one treatment is unlikely to be effective for such a variety of symptoms and causes. Knowing more about the disease’s diversity will allow researchers to design new drugs that target specific groups of patients, as well as to apply the existing drugs more effectively to those patients who are most likely to benefit from them.
1) D. Chaussabel et al. 2008. Immunity 29: 150-164.
2) R. Banchereau et al. 2016. Cell 165: 551-565.
3) E. Der et al. 2019. Nature Immunology [e-pub ahead of print, May 20, 2019]