Looking at Iron as a Trigger for Lupus Nephritis
Looking at Iron as a Trigger for Lupus Nephritis

As the provider of life-giving oxygen to organ systems through its role in red blood cell production — the health benefits of iron are tremendous. This essential element is vital for proper growth throughout the body and for robust cellular health.

But what happens when a good thing goes bad, and iron makes cells die?

This process — ferroptosis — is the focus of a Lupus Research Alliance-funded investigation that is currently being conducted by Erika Boesen, PhD, at the University of Nebraska Medical Center in Omaha, NE. Dr. Boesen is studying iron and ferroptosis to gain a better understanding of lupus — particularly lupus nephritis and renal failure.

The term ferroptosis is derived from the Greek word ptosis, meaning “a fall,” and ferrum, the Latin word for iron. It describes a form of regulated cell death in which iron appears to  be a factor.

Dr. Erika Boesen believes ferroptosis may play an important role in lupus nephritis.

“Iron doesn’t just transport oxygen around in red blood cells — it can also promote free radical activity that can damage cells of the body,” explains Dr. Boesen. “Ferroptosis is a particular type of cell death that occurs when iron has generated free radicals that overwhelm the antioxidant defenses of the cells.”

Connecting this back to lupus, Dr. Boesen is now building on the findings of her first Lupus Research Alliance grant to learn how much of a factor iron is to renal damage in lupus. In murine models, Dr. Boesen discovered an increase of iron in the kidneys. “We found that iron did contribute to lupus nephritis,” said Dr. Boesen. “But we still need to understand how … and I’m grateful for the additional support I have received from the Lupus Research Alliance … to continue this work.”

Ferroptosis is a relatively new field of study, and the tools to investigate it are few and far between at this stage. But a small number of chemicals have been identified that may stop this type of cellular death from happening. “The particular chemical that I am going to use is pretty specific to ferroptosis and this iron-mediated, free radical pathway,” shared Dr. Boesen. “So to block ferroptosis, my approach is pharmacological.”

If Dr. Boesen can successfully block ferroptosis, she may have found a way to block certain types of kidney damage. But she also wants to know if the debris from these cells is recognized by the immune system and if it is responsible for provoking further inflammatory responses.

As a second-time grant awardee, Dr. Boesen has much enthusiasm for the Lupus Research Alliance.  “This amazing organization does a great job in bringing in investigators who may not have worked exclusively in lupus research,” she said. “The Lupus Research Alliance allows researchers like me to explore new ideas — and bringing a more diverse group of minds to the complexities of lupus has only proven to be a good thing.”

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