A Novel, Potent and Selective TLR7/8 Small Molecule Inhibitor Blocks TLR7/8 Pathway in the Presence of HCQ and Demonstrates Robust Preclinical Efficacy in Lupus Models
Abstract format and assignment number: Poster 0085
Presenting author: C Shang (USA)
Date: Saturday, 16th November 2024
This study investigates a novel, selective TLR 7/8 inhibitor as a potential therapeutic addition to hydroxychloroquine in systemic lupus erythematosus (SLE). While HCQ suppressed TLR9 activation in SLE patient blood samples, TLR7/8 pathways remained active, indicating HCQ’s limited effect on TLR7/8. The TLR7/8 inhibitor effectively blocked TLR7/8-induced cytokine production and immune cell activation in vitro and improved disease markers such as survival, proteinuria and renal histopathology in murine lupus models. These findings support the combined use of TLR7/8 inhibition with HCQ to better target lupus pathogenesis.
Anti-HSP90α as a Protective Natural Antibody Against Secondary Antiphospholipid Syndrome in Systemic Lupus Erythematosus
Abstract format and assignment number: Poster 0098
Presenting author: M Barguil Macedo (USA)
Date: Saturday, 16th November 2024
This study explored the role of anti-HSP90α IgG antibodies in systemic lupus erythematosus and their potential protective effect against secondary antiphospholipid syndrome. Using plasma samples from two cohorts, anti-HSP90α IgG levels were measured in SLE patients and controls. SLE patients with APS showed significantly lower anti-HSP90α IgG levels compared to those without APS. In vitro, anti-HSP90α IgG reduced platelet activation markers (TSP-1, PF-4), suggesting it may inhibit HSP90-induced platelet activation, potentially reducing thrombosis risk in APS. This highlights a novel, protective role of anti-HSP90α IgG in SLE-related APS.
Novel Autoantibodies Identified in the Antiphospholipid Syndrome
Abstract format and assignment number: Poster 0105
Presenting author: S Hu (China)
Date: Saturday, 16th November 2024
This study identifies novel autoantibodies in APS using a proteome microarray. Six candidate autoantibodies (SULT2B1, NPM1, AGO1, SERPINB2, ACVR2B, IRAK4) were validated by ELISA, with anti-SULT2B1 and anti-AGO1 elevated in primary APS and anti-NPM1 associated with secondary APS, SLE, cardiac valve issues and triple antibody positivity. These findings highlight potential new diagnostic markers for APS, pending further validation.
External Validation and Extension of Population-Based Systemic Lupus Erythematosus Risk Prediction Models Using Genetics, and Lifestyle and Environmental Factors
Abstract format and assignment number: Poster 0843
Presenting author: JJE Koopman (USA)
Date: Saturday, 16th November 2024
This study validated systemic lupus erythematosus risk prediction models using genetic, lifestyle and environmental factors in the Mass General Brigham Biobank, involving 535 SLE patients and 2,135 matched controls. Three multivariable models were compared, including genetic risk scores and lifestyle/environmental factors such as smoking, alcohol use, obesity and depression. Model 3, which combined genetics with lifestyle and environmental factors, achieved the highest discrimination (AUC 0.81–0.82) for predicting SLE. These models could potentially support screening in at-risk populations, leveraging accessible genetic and lifestyle data for prevention efforts.
Allogenic CD19 CAR NK Cells Therapy in Refractory Systemic Lupus Erythematosus: An Open-label, Single Arm, Prospective and Interventional Clinical Trial
Abstract format and assignment number: Oral presentation L17
Presenting author: Y Yu (China)
Date: Tuesday, 19th November 2024
This study assessed the safety and efficacy of CD19-targeting CAR-NK cell therapy in 20 patients with severe, refractory systemic lupus erythematosus. After preconditioning with cyclophosphamide and fludarabine, patients received CAR-NK infusions, with median follow-up of 5 months. B-cell recovery occurred within 2-3 months, with mild cytokine release syndrome in 2 patients and no severe adverse events. Among those followed for over 6 months, 50% achieved DORIS-defined remission, and 75% achieved lupus low disease activity state, indicating potential for durable remission in SLE.
Omar Dhrif MD
Omar is an internal medicine specialist from University Tunis El Manar, and an internal medicine fellow at Dijon University Hospital, France. His main clinical and research interests focus on vasculitis, global access to healthcare and educational therapy. Omar is the past-treasurer of the Tunisian Association of Young Internists, co-founder of the Francophonic Young Internists Group, member of the Research Committee of the Tunisian Society of Internal Medicine and American College of Rheumatology Social Media Ambassador. Omar is a member of the EMEUNET Social Media sub-committee.