Extent and patterns of off-label use of rituximab for SLE

Sanz, Iñaki

doi:10.1038/nrrheum.2016.191

Cited by 13 publications

(9 citation statements)

References 10 publications

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“…The identification of a population of atypical memory T-bet + CD11c + B cells in patients with SLE raises the possibility that targeting this population may open new therapeutic opportunities for this complex disease, as the efficacies of B cell depletion therapy by targeting whole B cells in patients with SLE are highly variable 1 22. Particularly, it was reported that an expanded population of CD19 hi AtMs in patients with SLE predicts a poor clinical response to rituximab treatment 8.…”

Section: Introductionmentioning

confidence: 99%

Lupus-associated atypical memory B cells are mTORC1-hyperactivated and functionally dysregulated

Guo

et al. 2019

Ann Rheum Dis

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ObjectivesA population of atypical memory B cells (AtMs) are greatly expanded in patients with active lupus, but their generation and pathophysiological roles are poorly defined. The aim of this study was to comprehensively characterise lupus AtMs with a purpose to identify therapeutic clues to target this B cell population in lupus.MethodsPeripheral B cell subsets were measured by flow cytometry. Sorting-purified B cell subsets were subject to RNA sequencing and functional studies. Plasma cytokines and secreted immunoglobulins were detected by Luminex or ELISA. In situ renal B cells were detected by multiplexed immunohistochemistry.ResultsCD24−CD20hi AtMs were strongly increased in two Chinese cohorts of patients with treatment-naïve lupus. Gene expression profile indicated that B cell signalling and activation, lipid/saccharide metabolism and endocytosis pathways were abnormally upregulated in lupus AtMs. In addition, the mammalian target of rapamycin complex 1 (mTORC1) pathway was remarkably activated in lupus AtMs, and blocking mTORC1 signalling by rapamycin abolished the generation of T-bet+ B cells and terminal differentiation of lupus AtMs. Furthermore, lupus AtMs displayed a dysfunctional phenotype, underwent accelerated apoptosis, poorly co-stimulated T cells and produced proinflammatory cytokines. Interestingly, lupus AtMs were in a paradoxically differentiated status with markers pro and against terminal differentiation and enriched with antinucleosome reactivity. Finally, AtMs were accumulated in the kidneys of patients with lupus nephritis and associated with disease severity.ConclusionsThese findings demonstrated that mTORC1-overactivated lupus AtMs are abnormally differentiated with metabolic and functional dysregulations. Inhibiting mTORC1 signalling might be an attractive option to target AtMs and to improve therapeutic effectiveness in patients with lupus.

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Section: Introductionmentioning

confidence: 99%

Lupus-associated atypical memory B cells are mTORC1-hyperactivated and functionally dysregulated

Guo

et al. 2019

Ann Rheum Dis

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“…РТМ широко и с большим успехом используется при СКВ в клинической практике [108] и включен в международные [109][110][111][112][113] рое вошли пациенты с активной СКВ без поражения почек, и LUNAR (Lupus Nephritis Assesment with Rituximab) [116] -с волчаночным нефритом (ВН), «первичные конечные точки», отражающие эффективность терапии, достигнуты не были (табл. 7).…”

Section: системные васкулитыunclassified

Prospects for Anti-B-Cell Therapy in Immuno-Inflammatory Rheumatic Diseases

Насонов

Бекетова²,

Ананьева³

et al. 2019

Naučno-praktičeskaâ revmatologiâ

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“…While some B cell-targeting therapies generate promising results, the efficacies of certain trials are variable, indicating a highly heterogeneous feature of the B-cell compartment in SLE. 1,6,7 B-cell aberrations in SLE are reflected in multiple aspects. Transitional B (Btr) cells and plasmablasts are greatly expanded while IgM + memory B cells are decreased in active SLE patients.…”

Section: Introductionmentioning

confidence: 99%

Type I interferons promote the survival and proinflammatory properties of transitional B cells in systemic lupus erythematosus patients

Liu

Guo

et al. 2018

Cell Mol Immunol

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A hallmark of systemic lupus erythematosus (SLE) is the breaking of B-cell tolerance with the generation of high-affinity autoantibodies; however, the antibody-independent features of the B-cell compartment in SLE are less understood. In this study, we performed an extensive examination of B-cell subsets and their proinflammatory properties in a Chinese cohort of new-onset SLE patients. We observed that SLE patients exhibited an increased frequency of transitional B cells compared with healthy donors and rheumatoid arthritis patients. Plasma from SLE patients potently promoted the survival of transitional B cells in a type I IFN-dependent manner, which can be recapitulated by direct IFN-α treatment. Furthermore, the effect of IFN-α on enhanced survival of transitional B cells was associated with NF-κB pathway activation and reduced expression of the pro-apoptotic molecule Bax. Transitional B cells from SLE patients harbored a higher capacity to produce proinflammatory cytokine IL-6, which was also linked to the overactivated type I IFN pathway. In addition, the frequency of IL-6-producing transitional B cells was positively correlated with disease activity in SLE patients, and these cells were significantly reduced after short-term standard therapies. Thus, the current study provides a direct link between type I IFN pathway overactivation and the abnormally high frequency and proinflammatory properties of transitional B cells in active SLE patients, which contributes to the understanding of the roles of type I IFNs and B cells in the pathogenesis of SLE.

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Extent and patterns of off-label use of rituximab for SLE

Abstract: Despite conflicting evidence from clinical trials, rituximab continues to be used off-label in the treatment of systemic lupus erythematosus (SLE). A new study has now investigated the use of this drug for SLE in Europe, including indications for use and patient characteristics.

Cited by 13 publications

References 10 publications

Lupus-associated atypical memory B cells are mTORC1-hyperactivated and functionally dysregulated

Lupus-associated atypical memory B cells are mTORC1-hyperactivated and functionally dysregulated

Prospects for Anti-B-Cell Therapy in Immuno-Inflammatory Rheumatic Diseases

Type I interferons promote the survival and proinflammatory properties of transitional B cells in systemic lupus erythematosus patients

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