The 2023 Iva Dostanic, MD, PhD, Physician-Scientist Trainee Award Medical Grand Rounds (MGR) lecture was presented by Irene Chernova, MD, PhD, assistant professor of medicine (nephrology), on Thursday, June 22, 2023.
Chernova presented the MGR lecture, “Lympocytes, Sodium, and Autoimmunity: A Lupus Tale” after being selected as the awardee of the annual honor and lecture. The special MGR lecture and award was created in memory of Iva Dostanic, MD, PhD, a trainee in the Department of Internal Medicine who succumbed to ovarian cancer in December 2011.
In the grand rounds, Chernova began by outlining what listeners would learn about systemic lupus erythematosus (SLE) and the role of the adaptive immune system, including the understanding of how lymphocytes adapt to unique tissue environments that lead to autoimmune pathology, and the interrelationship between sodium and autoimmunity.
Systemic lupus erythematosus (SLE, lupus) is an autoimmune disease that affects nearly a quarter million individuals across the U.S. The diagnostic criteria is complex, and it can be challenging to diagnose because it impacts multiple organs.
One of the major organs lupus affects is the kidney. Also known as lupus nephritis, it is the leading cause of death for those with the disease. In patients with lupus, roughly 50 percent of those have lupus nephritis, which can lead to end stage renal disease–requiring transplantation and/or dialysis.
“If we treat the disease, we can impact patient survival in a positive way, but in order to have better treatments, we need to have an understanding of what the pathogenesis is, and it’s quite complicated,” states Chernova.
In Chernova’s research, she explores how B cells, also known as B lymphocytes, contribute to lupus nephritis and to what extent. She explains that when patients receive treatment that deplete B cells, severity of the disease lessens, but that treatment is not specifically targeting those present in the kidney.
“We know that B cells overall have some role, but we still don’t know what the kidney B cells are doing, necessarily, since we are getting rid of the cells everywhere.”
She explains that the kidney is the prototypical sodium-rich organ and that the sodium could impact survival of these cells. Sodium negatively affects function of other lymphocytes in autoimmune disease, but sodium’s effect on B cells remains largely uncharacterized.
“When I was starting this project and looking at literature, it wasn’t very clear what this [prior literature on sodium and lymphocytes] had to do with the kidney and what cells were involved. What was of extreme interest to me was how these lymphocytes are able to survive and adapt in [an] environment that they are not normally meant to be in. The kidney is not a very friendly place. I wanted to understand, is there something about the lupus B cell that makes it different that allows it to survive in the kidney? And how do lymphocytes survive the hypertonic kidney environment in lupus nephritis?”
In experiments, Chernova used flow cytometry to quantify and characterize kidney lymphocytes. Some of her findings include Na+-K+-ATPase expression is higher in the kidneys, compared to spleens, of lupus-prone animals.
While discussing the research, Chernova made mention about how Dostanic also studied isoforms of Na+-K+-ATPase in her PhD studies. "I didn't know until recently that Iva had also worked on [this], which is cool."
She discussed the findings further. “Research showed that kidney B cells likely utilize Na+-K+-ATPase to survive the salty kidney environment. Manipulation of Na+-K+-ATPase, using genetic and pharmacological tools, resulted in a depletion of B cells in the kidney without affecting B cells elsewhere in the body. There was also evidence of less protein in the urine, which is one of the markers of kidney damage in lupus nephritis.”
Chernova is now investigating the mechanisms by which kidney B cells may mediate the damage leading to the protein in the urine and looks forward to making further contributions on lupus nephritis.
To learn more, the full lecture can be found on the Department of Internal Medicine’s intranet.
Yale’s Section of Nephrology is committed to excellence in patient care, research, and education with the goal for both their faculty and trainees to be national and international leaders in the field of academic nephrology. To learn more about their mission and work, visit Nephrology.