CD20+ B-cell depletion therapy suppresses murine CD8+ T-cell–mediated immune thrombocytopenia

Guo, Li; Kapur, Rick; Aslam, Rukshana; Speck, Edwin R.; Zufferey, Anne; Zhao, Yajing; Kim, Michael; Lazarus, Alan H.; Ni, Heyu; Semple, John W.

doi:10.1182/blood-2015-06-655126

Cited by 50 publications

(43 citation statements)

References 24 publications

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“…Although a detailed analysis of rituximab pharmacodynamics in the spleen goes beyond the aim of this review, we would like to mention that this monoclonal antibody could act in a much more complicated way than simply depleting splenic B-cell. There is evidence, indeed, that by inducing important alterations in the white pulp microenvironment, it could affect also T-cell function and the process of selection of auto-reactive B-cells [66,67,68]. …”

Section: Role Of the Spleen In The Disposition Of Monoclonal Antibmentioning

confidence: 99%

Emerging Role of the Spleen in the Pharmacokinetics of Monoclonal Antibodies, Nanoparticles and Exosomes

Cataldi

Vigliotti

Mosca

et al. 2017

IJMS

207

151

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After being absorbed, drugs distribute in the body in part to reach target tissues, in part to be disposed in tissues where they do not exert clinically-relevant effects. Therapeutically-relevant effects are usually terminated by drug metabolism and/or elimination. The role that has been traditionally ascribed to the spleen in these fundamental pharmacokinetic processes was definitely marginal. However, due to its high blood flow and to the characteristics of its microcirculation, this organ would be expected to be significantly exposed to large, new generation drugs that can hardly penetrate in other tissues with tight endothelial barriers. In the present review, we examine the involvement of the spleen in the disposition of monoclonal antibodies, nanoparticles and exosomes and the possible implications for their therapeutic efficacy and toxicity. The data that we will review lead to the conclusion that a new role is emerging for the spleen in the pharmacokinetics of new generation drugs, hence suggesting that this small, neglected organ will certainly deserve stronger attention by pharmacologists in the future.

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Section: Role Of the Spleen In The Disposition Of Monoclonal Antibmentioning

confidence: 99%

Emerging Role of the Spleen in the Pharmacokinetics of Monoclonal Antibodies, Nanoparticles and Exosomes

Cataldi

Vigliotti

Mosca

et al. 2017

IJMS

207

151

View full text Add to dashboard Cite

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“…45 In a mouse model of ITP, B-cell depletion was shown to impair proliferation of CD8 + T cells in an IL-2dependent manner, resulting in increased platelet counts. 46 Of note, IL-10 + B cells may induce Tregs in autoimmunity 47 and cancer. 48 Thus, the increase in IL-10 + B cells as well as CD5 + B cells, which may represent overlapping subsets, 16,21 is compatible with induction of Tregs.…”

Section: Association Between B-cell Subsets and Platelet Numbers Afmentioning

confidence: 99%

Effects of rituximab and dexamethasone on regulatory and proinflammatory B‐cell subsets in patients with primary immune thrombocytopenia

Gudbrandsdottir

Brimnes

Køllgaard

et al. 2017

European J of Haematology

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Objective: To investigate the cytokine production and surface marker composition of B cells in adult patients with newly diagnosed primary immune thrombocytopenia (ITP) before and 12 months after treatment with rituximab + dexamethasone (RTX+DXM) or dexamethasone (DXM). Methods:Peripheral blood mononuclear cells were isolated from nine patients treated with RTX+DXM, seven patients treated with DXM, and seven healthy donors.Expression of the cell-surface markers CD5, CD27, CD25, and CD19, and intracellular content of IL-6 and IL-10 were measured by flow cytometry.

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“…In addition, regulatory B cells, which function as immune response suppressors, have been reported to be deficient in active ITP (Li et al , ). Guo et al () provided the first mechanistic explanation for the regulation of CD8 + T‐cell responses by B cells. The efficacy of rituximab treatment in chronic ITP patients supports the pivotal roles of B cells in ITP (Provan et al , ; Zaja et al , ).…”

mentioning

confidence: 99%

Upregulation of CD72 expression on CD19⁺CD27⁺ memory B cells by CD40L in primary immune thrombocytopenia

Lyu

Hao

et al. 2017

Br J Haematol

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CD72 is a co-receptor of B cells and regulates B cell activation. Although aberrant expression of CD72 has been reported in primary immune thrombocytopenia (ITP), it is uncertain whether this aberrant expression is restricted to specific B cell subsets. Furthermore, the mechanisms that regulate CD72 expression are unknown. In this study, we found higher frequency of CD19 B cells, CD19 CD27 memory B cells and lower frequency of CD19 CD27 naive B cells in active ITP patients compared with controls and patients in remission. CD72 expression on CD19 CD27 cells was upregulated in active ITP patients and correlated with platelet count and anti-platelet autoantibodies. In vitro, CD40L could specifically induce CD72 upregulation on CD19 CD27 B cells. In combination with CD40L, interleukin (IL) 10 and BAFF (also termed TNFSF13B) further enhanced CD72 expression on CD19 CD27 B cells, whereas IL21 reduced CD72 upregulation. CD72mRNA expression after CD40L stimulation was increased in ITP patients and controls. Significant increase of CD40L on CD4 T cells was correlated with CD72 expression on CD19 CD27 B cells in ITP patients. In conclusion, upregulation of CD72 expression on CD27 memory B cells might take part in the pathogenesis of ITP. Elevated CD40L on CD4 cells combined with cytokines might contribute to the upregulation of CD72 expression on CD27 memory B cells.

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CD20+ B-cell depletion therapy suppresses murine CD8+ T-cell–mediated immune thrombocytopenia

Cited by 50 publications

References 24 publications

Emerging Role of the Spleen in the Pharmacokinetics of Monoclonal Antibodies, Nanoparticles and Exosomes

Emerging Role of the Spleen in the Pharmacokinetics of Monoclonal Antibodies, Nanoparticles and Exosomes

Effects of rituximab and dexamethasone on regulatory and proinflammatory B‐cell subsets in patients with primary immune thrombocytopenia

Upregulation of CD72 expression on CD19⁺CD27⁺ memory B cells by CD40L in primary immune thrombocytopenia

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CD20+ B-cell depletion therapy suppresses murine CD8+ T-cell–mediated immune thrombocytopenia

Cited by 50 publications

References 24 publications

Emerging Role of the Spleen in the Pharmacokinetics of Monoclonal Antibodies, Nanoparticles and Exosomes

Emerging Role of the Spleen in the Pharmacokinetics of Monoclonal Antibodies, Nanoparticles and Exosomes

Effects of rituximab and dexamethasone on regulatory and proinflammatory B‐cell subsets in patients with primary immune thrombocytopenia

Upregulation of CD72 expression on CD19+CD27+ memory B cells by CD40L in primary immune thrombocytopenia

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Upregulation of CD72 expression on CD19⁺CD27⁺ memory B cells by CD40L in primary immune thrombocytopenia