2012
DOI: 10.1038/nrneph.2012.141
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B-cell depletion in the treatment of lupus nephritis

Abstract: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is clinically heterogeneous and affects multiple organs. Lupus nephritis is the most frequent severe manifestation of SLE. Conventional immunosuppressive therapy has increased the life expectancy of patients diagnosed with lupus nephritis, but only 70-80% of patients respond to this treatment and its adverse effects are considerable. B cells are central to the pathogenesis of SLE and are, therefore, an attractive therapeutic target. B-cel… Show more

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Cited by 77 publications
(50 citation statements)
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“…Two large randomized phase 3 trials failed to demonstrate statistically significant superiority of B-cell depletion with either agent over standard-of-care therapy in patients with active proliferative lupus nephritis (156,157). However, a trend toward more patients reaching complete or partial remission at 1 year (primary endpoint), and improved proteinuria and renal function (secondary endpoints) was observed in the B-lymphocyte depletion groups (109,156,157). Patients treated for class 3 lupus nephritis attained complete remission most successfully, while those with class 5 lupus nephritis were the least likely to respond (109).…”
Section: Role In Gnmentioning
confidence: 99%
See 1 more Smart Citation
“…Two large randomized phase 3 trials failed to demonstrate statistically significant superiority of B-cell depletion with either agent over standard-of-care therapy in patients with active proliferative lupus nephritis (156,157). However, a trend toward more patients reaching complete or partial remission at 1 year (primary endpoint), and improved proteinuria and renal function (secondary endpoints) was observed in the B-lymphocyte depletion groups (109,156,157). Patients treated for class 3 lupus nephritis attained complete remission most successfully, while those with class 5 lupus nephritis were the least likely to respond (109).…”
Section: Role In Gnmentioning
confidence: 99%
“…Altered numbers and/ or function of Bregs have been described in SLE and AAV, contributing to disease pathogenesis and/or relapse (102,(105)(106)(107). The presence of potent Bregs could explain why pan-depletion of B cells in humans using anti-CD20 (rituximab) has led to paradoxical or unsatisfactory clinical results in renal transplantation, as well as autoimmune renal disease (108,109). Similarly, indiscriminate use of antibodies targeting BAFF could be detrimental because Breg development and IL-10 production appear to depend on BAFF signaling through TACI (110,111).…”
Section: Bregsmentioning
confidence: 99%
“…In rheumatoid arthritis (RA), RTX has been licensed at a fixed dose (1,000 mg on days 1 and 2), though this arbitrary regimen was chosen by the manufacturer in both phase II and III trials [11]. By analogy with RA, this regimen is now increasingly used off-label for many other autoimmune diseases [12,13]. The aim of our large French multicenter retrospective study was to compare the efficacy and safety of two RTX regimens in adult's ITP.…”
Section: Introductionmentioning
confidence: 99%
“…88 Meanwhile, it is clear that B cells in SLE also contribute to autoimmunity and tissue inflammation in many other ways, which increases the hope that depleting or modulating B cells would result in major benefits in SLE and LN. 89 This led to the development of the fully humanized anti-CD20 antibody (rituximab), the anti-CD22 antibody (epratuzumab), and to anti-BlyS (belimumab). Because the randomized placebo-controlled Lupus Nephritis Assessment with Rituximab trial failed to demonstrate a benefit of add-on rituximab for the induction therapy of incident LN class III/IV/V, this approach to B cell depletion still has questions.…”
Section: Novel Moieties That Target Specific Leukocyte Subsetsmentioning
confidence: 99%
“…Other B cell-directed strategies include atacicept (TACI-Ig), LY2127399 (anti-BAFF), and anti-BR3 (anti-BAFF-R). 89 Dendritic cell-T cell interaction is a target of costimulatory ligand/receptor blockers such as CTLA-4-Ig (abatacept). This drug blocks the interaction of CD80 and CD86 on antigen-presenting cells with CD28 on T cells, which suppresses T cell activation.…”
Section: Novel Moieties That Target Specific Leukocyte Subsetsmentioning
confidence: 99%