Re-engineering Immune Cells Opens Door to Promising Therapy for Lupus Kidney Inflammation

Research Published in Nature Communications and Funded in Part by the Lupus Research Alliance Could Correct a Defect in Lupus

NEW YORK, Feb. 6, 2024 /PRNewswire/ -- Research featured in Nature Communications highlights a novel approach that re-engineers a person's own immune cells to suppress the overactive immune system that occurs in lupus nephritis, a serious and potentially life-threatening inflammation of the kidneys. With funding in part from the Lupus Research Alliance (LRA), associate professor Joshua Ooi, Ph.D. and his team at the Centre for Inflammatory Disease, Monash Health in Australia, developed an innovative method that could enable multiple targeted therapies not only for lupus but other autoimmune diseases as well.

T cells direct the immune system's response to potential threats by identifying and attacking harmful invaders like viruses and bacteria. In healthy individuals, a specific type of T cells called T regulatory cells (Tregs) prevent the immune system from continuing to react once an infection is cleared.  People with lupus often have fewer Tregs or their Tregs do not work properly, contributing to the body's attack on its own tissues. In this groundbreaking study led by Peter Eggenhuizen and Rachel Cheong, Ph.D., the team developed a way to reprogram a patient's own defective Tregs to restore immune balance and offer a potential targeted treatment for people with lupus. 

Current treatment options are limited, and drugs that suppress the immune system, like steroids, can cause harmful side effects. Dr. Ooi noted, "This major discovery shows that we can specifically correct the misguided immune response in patients. This means that patients could rely less on drugs that suppress the entire immune system."

Restoring Regulatory Immune Cells to Do Their Job

People with lupus typically have antibodies that mistakenly target many of their own proteins, including one called Smith. Dr. Ooi and colleagues re-engineered Tregs from SLE patients to specifically target the Smith protein, restoring their ability to suppress the overactive immune system. When tested in cells from people with SLE, the Smith-specific Tregs reduced inflammatory molecules called cytokines, which are typically high in individuals with lupus nephritis. In a mouse model of lupus nephritis, the Smith-specific Tregs reduced disease severity and proteinuria (high level of protein in the urine) and prevented kidney damage, highlighting their therapeutic potential.

Dr. Ooi is a recipient of LRA's 2021 Lupus Innovation Award (LIA), which provides early-stage support for highly innovative approaches to major challenges in lupus research. He noted, "This scientific breakthrough would not have been possible without the generous and visionary funding of the LRA. Earlier LRA funding allowed my team to pursue the idea that patients' immune cells could be engineered to correct immune dysfunction. The Lupus Innovation Award then gave us the ability to test the effectiveness of these patient-derived engineered cells in a model of disease."

This work was done in collaboration with Eric Morand, M.D., Ph.D., esteemed Head of Rheumatology at Monash Health and the recipient of the LRA's 2022 Global Team Science Award.

"We are thrilled about this breakthrough by Dr. Ooi and his team," commented Teodora Staeva, Ph.D., Chief Scientific Officer at the LRA, "The development of this method is accelerating the path to personalized treatment and has the potential to provide an important new option for people with lupus nephritis who often take long-term immunosuppressants to manage their symptoms."

About Lupus
Lupus is a chronic, complex autoimmune disease that affects millions of people worldwide. More than 90 percent of people with lupus are women, often striking during the childbearing years of 15-45. Blacks/African Americans, Hispanics, Asians, and Native Americans are at two to three times greater risk than Caucasians for developing lupus. In lupus, the immune system, meant to defend against infections, produces antibodies that mistakenly recognize the body's own cells as foreign, prompting other immune cells to attack and potentially damage organs such as the kidneys, brain, heart, lungs, blood, skin, and joints.

About the Lupus Research Alliance
The Lupus Research Alliance is the largest non-governmental, non-profit funder of lupus research worldwide. The organization aims to transform treatment by funding the most innovative lupus research, fostering diverse scientific talent, and driving discovery toward better diagnostics, improved treatments and ultimately a cure for lupus. Because the Lupus Research Alliance's Board of Directors funds all administrative and fundraising costs, 100% of all donations goes to support lupus research programs. For more information, please visit the LRA at LupusResearch.org and on social media at: X, Facebook, LinkedIn, and Instagram.

Click here for 2.6.24 press release from Monash Health

SOURCE Lupus Research Alliance