For decades, scientists have focused largely on the immune system when searching for ways to treat lupus-related kidney disease. A landmark study involving Oklahoma Medical Research Foundation scientists offers a new perspective: The kidneys themselves may play a bigger role than previously thought.
Researchers examined kidney tissue one cell at a time to create a detailed map of what happens inside the kidneys of people with lupus nephritis, a complication of lupus that can cause permanent kidney damage. The findings reveal changes in both immune cells and kidney tissue cells that could eventually help explain why kidney damage occurs and why treatment does not work the same way for every patient.
“This large collaborative study brought together leaders in lupus nephritis from across the country to obtain and examine molecular data in lupus nephritis,” said Soumya Raychaudhuri, M.D., Ph.D., of Harvard Medical School and Brigham and Women’s Hospital. “We found that specialized immune cells called macrophages appear to be highly correlated with, and potentially driving, tissue damage.”
Macrophages can enter and reside in tissues, including the kidney, where they normally regulate inflammation and respond to injury. In this study, particular macrophage populations within the kidney were associated with inflammation, tissue damage and scarring.
“We’ve always thought that certain immune cells were responsible,” said OMRF Executive Vice President and Chief Medical Officer Judith James, M.D., Ph.D. “This study identified potential culprits and how they interact with the kidney tissue itself.”
Lupus is a chronic condition in which the body’s immune system mistakenly attacks its own healthy tissues and organs. It is a leading cause of death in young women between ages 15 and 45, with kidney damage disproportionately contributing to disease severity.
This discovery involved lupus experts from some of the nation’s premier medical and research institutions. They were brought together through a public-private partnership led by the National Institutes of Health and the Foundation for the National Institutes of Health.
Scientists analyzed tissue from about 160 people with lupus who underwent kidney biopsies due to concerning findings in their urine. OMRF researchers processed kidney tissue samples, performed blood and urine testing, organized clinical data, and built the research infrastructure needed to connect information from individual patients with the molecular changes found in their kidneys.
“Lupus nephritis is not one disease with one underlying cause,” said James, who holds the Lou C. Kerr Endowed Chair in Biomedical Research at OMRF. “By identifying the different cellular processes that may be active in different patients, we may be able to better understand why some people respond to treatment while others do not.”
Raychaudhuri, who led the study, said this discovery lays the groundwork for future research to better understand the mechanisms of kidney damage in lupus nephritis and identify opportunities to intervene before irreversible injury occurs.
Their results were published in the journal Science Translational Medicine. OMRF’s role in the study was supported by grant UM2-AR067678 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the NIH.
This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
