The Lupus Research Alliance (LRA) is proud to showcase the groundbreaking work of its funded researchers presented at the 2024 ACR Convergence meeting held this November in Washington, D.C. From novel steroid-sparing strategies to precision immunotherapies, this year’s presentations promise to bring new insights and transformative approaches to systemic lupus erythematosus (SLE) and related autoimmune diseases.

LRA-Funded Research at ACR Convergence

Precision Immunotherapy for Antiphospholipid Syndrome (APS) – Abstract #0837

Maximilian Konig, MD, Assistant Professor of Medicine and Director, Cellular Therapy Program (Autoimmunity), Johns Hopkins University School of Medicine, and recipient of the LRA’s 2023 Lupus Innovation Award (LIA), is working on a groundbreaking approach to treating antiphospholipid syndrome (APS), a condition that often affects lupus patients and can lead to dangerous blood clots and pregnancy complications. Current treatments suppress the entire immune system, which can increase infection risk. Dr. Konig’s team developed a more targeted solution called bispecific autoantigen-T cell engaging (BaiTE) antibodies, which selectively attack a subset of harmful cells responsible for APS, leaving the rest of the immune system intact. This promising “off-the-shelf” (pre-manufactured and ready-to-use) therapy could revolutionize the way autoimmune diseases like APS are treated, offering precision without the side effects.

Understanding Pregnancy Loss in Lupus Patients – Abstract #1702

Anne Davidson, MBBS, Professor of Molecular Medicine, Donald and Barbara Zucker School of Medicine, Hofstra/Northwell, Investigator, Feinstein Institutes for Medical Research, and recipient of the LRA 2023 LIA and 2016 Lupus Mechanisms and Targets Award (LMTA), has developed a new model to study pregnancy loss associated with antiphospholipid antibodies, which are common in lupus. By generating a special strain of mice that produces a human version of TLR8, a pro-inflammatory signaling molecule, her team has uncovered crucial insights into how these antibodies disrupt placental development, leading to pregnancy loss. Their findings, presented by Yunwei Xia, BA, Feinstein Institutes for Medical Research, suggest that the loss of immune cells called NK cells (a type of white blood cell) in the uterus plays a significant role in these complications. This research could pave the way for new interventions to prevent pregnancy loss in women with lupus.

Markers of Brain Injury in Children with Lupus – Abstract #2625

Research by Andrea Knight, MD, Pediatric Rheumatologist and Clinician-Investigator, Division of Rheumatology, Associate Scientist, Neurosciences and Mental Health Program, The Hospital for Sick Children (SickKids), and Assistant Professor of Pediatrics, University of Toronto, focuses on the impact of lupus on cognitive function in children. Many young people with lupus experience difficulties with tasks like problem-solving and multitasking, which may be linked to brain inflammation, medications, or fatigue. With funding from the LRA 2022 Diversity in Lupus Research Career Development Award, Dr. Knight’s team identified blood markers of brain injury that correlate with impaired cognitive function, offering a potential tool for doctors to assess and monitor brain health in children with lupus. This could lead to earlier intervention and better management of neuropsychiatric symptoms in lupus patients. These findings were presented by Oscar Mwizerwa, MD, University of Toronto, and The Hospital for Sick Children.

Uncovering Why Lupus Disproportionately Affects Women

Research by Montserrat Anguera, PhD, Associate Professor, University of Pennsylvania School of Veterinary Medicine, supported by her 2019 LMTA, explores why lupus impacts women more often than men, focusing on the unique role of the X chromosome, a carrier of genetic information that plays a key role in the biological differences between females and males. To balance gene expression between females and males and to prevent females from making twice as many gene products (due to their having two X chromosomes), a process called X chromosome inactivation occurs in every cell in a female’s body. Dr. Anguera found that this process depends on NF-κB signaling, which is essential for keeping the inactive X chromosome silenced. This insight sheds light on how defects in NF-κB regulation of X chromosome inactivation may contribute to this sex bias in lupus.

These innovative projects, funded by the LRA, highlight the diverse and impactful research being done to better understand and treat lupus.

Engineered Cell Therapies and Steroid Replacement: Promising Frontiers for Lupus Treatment

In addition to the LRA-funded studies presented at ACR Convergence 2024, the LRA is proud to highlight investigators at the forefront of novel therapies for lupus, including engineered cell therapies and steroid replacements.

2022 LRA Global Team Science Award recipient Eric Morand, MD, PhD, Head of Rheumatology, Monash Health, has made significant strides in finding alternatives to steroids for lupus treatment. Steroids, though widely used, can lead to serious side effects like organ damage. Dr. Morand and his team are focused on a protein called GILZ, which mimics the anti-inflammatory effects of steroids but without the harmful consequences. Their study, presented by Iolanda Miceli, Monash University, identified an enzyme, “E3-X,” that breaks down GILZ, leading to inflammation. By blocking this enzyme, they successfully increased GILZ levels and reduced inflammation in lupus models, opening the door to potential new treatments that could replace steroids for lupus patients. The research presented at ACR Convergence 2024 paved the way for the LRA 2024 Translational Bridge Award granted to Sarah Jones, PhD, Head of the Rheumatology Research Laboratory, School of Clinical Sciences, Monash Health, through which she aims to develop a treatment to boost GILZ.

Among the many cutting-edge therapies being highlighted, engineered cell therapies stand out as a promising frontier for treating lupus. Georg Schett, MD, Vice President, Research, Head of Department, Internal Medicine 3, Friedrich-Alexander-Universität Erlangen-Nürnberg, and recipient of the LRA 2024 Lupus Insight Prize, presented, along with his team members, updates on the groundbreaking potential of CD19 CAR-T cell therapy in lupus and other autoimmune diseases. His team’s latest findings show that this therapy can induce long-lasting drug-free remission with minimal adverse events in patients with severe, treatment-resistant lupus, offering hope to those for whom traditional immunosuppressive therapies have failed.

These innovative approaches are at the forefront of transforming lupus treatment, and the LRA is proud to support investigators like Drs. Schett, Morand, and Jones, who are leading these efforts, demonstrating the potential to revolutionize care for people with lupus.

The LRA remains dedicated to supporting research across the full spectrum to achieve its research strategic goals and enable patient-centered outcomes. The groundbreaking progress presented at ACR Convergence 2024 represents a significant step forward toward improved therapies, diagnostics, and biomarkers for those living with lupus.