Only Follow-Up of Memory B Cells Helps Monitor Rituximab Administration to Patients with Neuromyelitis Optica Spectrum Disorders

Lebrun, C.; Cohen, M.; Rosenthal-Allieri, Maria Alessandra; Bresch, Saskia; Benzaken, Sylvia; Marignier, Romain; Seitz-Polski, Barbara; Ticchioni, Michel

doi:10.1007/s40120-018-0101-4

Cited by 33 publications

(21 citation statements)

References 38 publications

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“…Moreover, in contrast to total CD19+ cell detected with routine techniques, the addition of assessment of subpopulations of B cells using multicolor flow cytometry, namely CD19+ CD27+ memory B cells, have been shown to be a reliable marker that correlates with biological relapse. In this study, the authors found the reemergence of naïve B cells prior to the emergence of CD19+ CD27+ memory B cells in some cases, and that this reemergence did not correlate with total B cell emergence, allowing for a decrease in the frequency of rituximab infusions ( 81 ). Low dose rituximab regimens have been described by several groups ( 82 – 84 ), but notably, dosing may need to be more frequent with lower doses.…”

Section: Review Of Current Knowledgementioning

confidence: 83%

Pediatric NMOSD: A Review and Position Statement on Approach to Work-Up and Diagnosis

Tenembaum

Yeh

2020

Front. Pediatr.

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Neuromyelitis Optica Spectrum Disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS) primarily affecting the optic nerves and spinal cord, but also involving other regions of the CNS including the area postrema, periaqueductal gray matter, and hypothalamus. Knowledge related to pediatric manifestations of NMOSD has grown in recent years, particularly in light of newer information regarding the importance of not only antibodies to aquaporin 4 (AQP4-IgG) but also myelin oligodendrocyte glycoprotein (MOG-IgG) in children manifesting clinically with this syndrome. In this review, we describe the current state of the knowledge related to clinical manifestations, diagnosis, and chronic therapies for children with NMOSD, with emphasis on literature that has been published in the last 5 years. Following the review, we propose recommendations for the assessment/follow up clinical care, and treatment of this population.

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Section: Review Of Current Knowledgementioning

confidence: 83%

Pediatric NMOSD: A Review and Position Statement on Approach to Work-Up and Diagnosis

Tenembaum

Yeh

2020

Front. Pediatr.

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“…Cluster B1 expressed naive B cells related genes ( CXCR4 , CD83 , and IGHD ) ( 15 ), and CD27 was expressed in clusters B2 and B6. Cluster B2 was similar to memory B cell ( 32 ), and cluster B6 expressed high levels of immunoglobulin genes ( IGHA1 , IGHG1 , and IGLC2 ), which defined them as plasma cells. Cluster B5 exhibited the expression of CLEC4C , GZMB , PTPRS , and IL3RA , which is similar to the phenotype of pDC-like cells ( 14 ).…”

Section: Resultsmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4+ T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren’s Syndrome

et al. 2021

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ObjectivePrimary Sjögren’s syndrome (pSS) is a systemic autoimmune disease, and its pathogenetic mechanism is far from being understood. In this study, we aimed to explore the cellular and molecular mechanisms that lead to pathogenesis of this disease.MethodsWe applied single-cell RNA sequencing (scRNA-seq) to 57,288 peripheral blood mononuclear cells (PBMCs) from five patients with pSS and five healthy controls. The immune cell subsets and susceptibility genes involved in the pathogenesis of pSS were analyzed. Flow cytometry was preformed to verify the result of scRNA-seq.ResultsWe identified two subpopulations significantly expand in pSS patients. The one highly expressing cytotoxicity genes is named as CD4+ CTLs cytotoxic T lymphocyte, and another highly expressing T cell receptor (TCR) variable gene is named as CD4+ TRAV13-2+ T cell. Flow cytometry results showed the percentages of CD4+ CTLs, which were profiled with CD4+ and GZMB+ staining; the total T cells of 10 patients with pSS were significantly higher than those of 10 healthy controls (P= 0.008). The expression level of IL-1β in macrophages, TCL1A in B cells, as well as interferon (IFN) response genes in most cell subsets was upregulated in the patients with pSS. Susceptibility genes including HLA-DRB5, CTLA4, and AQP3 were highly expressed in patients with pSS.ConclusionsOur data revealed disease-specific immune cell subsets and provided some potential new targets of pSS. Specific expansion of CD4+ CTLs may be involved in the pathogenesis of pSS, which might give valuable insights for therapeutic interventions of pSS.

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“…Moreover, memory B cells were shown to worsen the severity of NMOSD [ 184 ]. In rituximab-treated NMOSD patients, elevated CD27 + memory B cells were reported to be a reliable marker for biological and clinical relapses after depletion [ 185 , 186 , 187 ]. In contrast, a depletion of memory B cells was associated with a clinical response to rituximab treatment [ 188 ].…”

Section: Ineffectiveness and Failure Of Ms Therapeutics In Nmosdmentioning

confidence: 99%

Differential Effects of MS Therapeutics on B Cells—Implications for Their Use and Failure in AQP4-Positive NMOSD Patients

Traub

Häusser‐Kinzel

Weber

2020

IJMS

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B cells are considered major contributors to multiple sclerosis (MS) pathophysiology. While lately approved disease-modifying drugs like ocrelizumab deplete B cells directly, most MS medications were not primarily designed to target B cells. Here, we review the current understanding how approved MS medications affect peripheral B lymphocytes in humans. These highly contrasting effects are of substantial importance when considering these drugs as therapy for neuromyelitis optica spectrum disorders (NMOSD), a frequent differential diagnosis to MS, which is considered being a primarily B cell- and antibody-driven diseases. Data indicates that MS medications, which deplete B cells or induce an anti-inflammatory phenotype of the remaining ones, were effective and safe in aquaporin-4 antibody positive NMOSD. In contrast, drugs such as natalizumab and interferon-β, which lead to activation and accumulation of B cells in the peripheral blood, lack efficacy or even induce catastrophic disease activity in NMOSD. Hence, we conclude that the differential effect of MS drugs on B cells is one potential parameter determining the therapeutic efficacy or failure in antibody-dependent diseases like seropositive NMOSD.

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Only Follow-Up of Memory B Cells Helps Monitor Rituximab Administration to Patients with Neuromyelitis Optica Spectrum Disorders

Abstract: In contrast to total CD19+ cell, detected with the routine technique, CD19+ CD27+ memory B cells are a reliable marker for biological relapse and allow a decrease in the frequency of infusions.

Cited by 33 publications

References 38 publications

Pediatric NMOSD: A Review and Position Statement on Approach to Work-Up and Diagnosis

Pediatric NMOSD: A Review and Position Statement on Approach to Work-Up and Diagnosis

Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4+ T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren’s Syndrome

Differential Effects of MS Therapeutics on B Cells—Implications for Their Use and Failure in AQP4-Positive NMOSD Patients

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