Sun-374 B-Cell Depletion and Response in a Randomized, Controlled Trial of Obinutuzumab for Proliferative Lupus Nephritis

Rovin, BH; Furie, Richard; Aroca, Gustavo; Garg, Jay; Alvarez, Alexia; Fragoso‐Loyo, Hilda; Santillán, Elizabeth Zuta; Brunetta, P.; Schindler, Thomas; Looney, Cary M.; Hassan, Imran; Cascino, Matthew D.; Malvar, Ana

doi:10.1016/j.ekir.2020.02.913

Cited by 7 publications

(2 citation statements)

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“…Pre-clinical data showed the superior efficacy of obinutuzumab in B cell depletion compared with rituximab 24 . Recent results from the phase II NOBILITY study (NCT02550652) showed that obinutuzumab, when added to background immunosuppression comprising corticosteroids and mycophenolate, increased the rates of achieving primary and secondary efficacy endpoints, possibly related to a rapid and complete depletion of peripheral, memory, and naïve B cell subsets and plasmablasts 33 , 34 .…”

Section: Emerging Therapies Targeting B Lymphocytesmentioning

confidence: 99%

A review of advances in the understanding of lupus nephritis pathogenesis as a basis for emerging therapies

2020

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Lupus nephritis is an important cause of both acute kidney injury and chronic kidney disease that can result in end-stage renal disease. Its pathogenic mechanisms are characterized by aberrant activation of both innate and adaptive immune responses, dysregulation of inflammatory signaling pathways, and increased cytokine production. Treatment of lupus nephritis remains a challenging issue in the management of systemic lupus erythematosus since the clinical presentation, response to treatment, and prognosis all vary considerably between patients and are influenced by ethnicity, gender, the degree of chronic kidney damage, pharmacogenomics, and non-immunological modulating factors. Elucidation of the various immunopathogenic pathways in lupus nephritis has resulted in the development of novel therapies, including biologics that target specific antigens on B lymphocytes to achieve B cell depletion, agents that modulate B cell proliferation and development, drugs that block co-stimulatory pathways, drugs that target T lymphocytes primarily, and therapies that target complement activation, signaling pathways, pro-inflammatory cytokines, and neutrophil extracellular traps. This review will discuss recent advances in the understanding of disease pathogenesis in lupus nephritis in the context of potential emerging therapies.

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Section: Emerging Therapies Targeting B Lymphocytesmentioning

confidence: 99%

A review of advances in the understanding of lupus nephritis pathogenesis as a basis for emerging therapies

2020

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“…Furthermore, a significant proportion of SLE patients (20% to 50%) are at risk of developing LN within the first year following their initial diagnosis of SLE [ 5 ]. Despite recent breakthroughs in the development of new therapeutics, it is crucial to acknowledge that the remission rate for LN remains low, from 30% to 70% [ 6 , 7 , 8 , 9 , 10 , 11 ]. This fact holds significant importance because achieving remission in LN is intricately linked to the risk of progressing to end-stage kidney disease (ESKD).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Dysfunction in Systemic Lupus Erythematosus with a Focus on Lupus Nephritis

Halfon,

Tankeu,

Ribi

2024

IJMS

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Systemic lupus erythematosus (SLE) is an autoimmune disease affecting mostly women of child-bearing age. Immune dysfunction in SLE results from disrupted apoptosis which lead to an unregulated interferon (IFN) stimulation and the production of autoantibodies, leading to immune complex formation, complement activation, and organ damage. Lupus nephritis (LN) is a common and severe complication of SLE, impacting approximately 30% to 40% of SLE patients. Recent studies have demonstrated an alteration in mitochondrial homeostasis in SLE patients. Mitochondrial dysfunction contributes significantly to SLE pathogenesis by enhancing type 1 IFN production through various pathways involving neutrophils, platelets, and T cells. Defective mitophagy, the process of clearing damaged mitochondria, exacerbates this cycle, leading to increased immune dysregulation. In this review, we aim to detail the physiopathological link between mitochondrial dysfunction and disease activity in SLE. Additionally, we will explore the potential role of mitochondria as biomarkers and therapeutic targets in SLE, with a specific focus on LN. In LN, mitochondrial abnormalities are observed in renal cells, correlating with disease progression and renal fibrosis. Studies exploring cell-free mitochondrial DNA as a biomarker in SLE and LN have shown promising but preliminary results, necessitating further validation and standardization. Therapeutically targeting mitochondrial dysfunction in SLE, using drugs like metformin or mTOR inhibitors, shows potential in modulating immune responses and improving clinical outcomes. The interplay between mitochondria, immune dysregulation, and renal involvement in SLE and LN underscores the need for comprehensive research and innovative therapeutic strategies. Understanding mitochondrial dynamics and their impact on immune responses offers promising avenues for developing personalized treatments and non-invasive biomarkers, ultimately improving outcomes for LN patients.

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Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial

et al. 2021

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Sun-374 B-Cell Depletion and Response in a Randomized, Controlled Trial of Obinutuzumab for Proliferative Lupus Nephritis

Cited by 7 publications

References 0 publications

A review of advances in the understanding of lupus nephritis pathogenesis as a basis for emerging therapies

A review of advances in the understanding of lupus nephritis pathogenesis as a basis for emerging therapies

Mitochondrial Dysfunction in Systemic Lupus Erythematosus with a Focus on Lupus Nephritis

Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial

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