Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell–depleting therapy with rituximab

Stasi, Roberto; Cooper, Nichola; Poeta, Giovanni Del; Stipa, Elisa; Evangelista, Maria Laura; Abruzzese, Elisabetta; Amadori, Sergio

doi:10.1182/blood-2007-12-129262

Cited by 368 publications

(273 citation statements)

References 16 publications

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“…21,22 Published investigations offer some insight as to potential explanations for this apparent paradox. [23][24][25] First, podocytes express the B cell costimulatory molecule B7-1 in response to various pathologic stimuli, 26,27 and rituximab may delay the appearance of B7-1 on the podocytes, as in B cells of patients with non-Hodgkin lymphoma. 28 In support of this theory, abatacept, a blocker of costimulatory molecules, has been used with success in five cases of otherwise treatment-resistant FSGS.…”

Section: Discussionmentioning

confidence: 99%

Rituximab in Children with Steroid-Dependent Nephrotic Syndrome

Ravani

Rossi

Bonanni

et al. 2015

Journal of the American Society of Nephrology

161

142

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Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, noninferiority, randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1-16 years who had developed SDNS in the previous 6-12 months and were maintained in remission with high prednisone doses ($0.7 mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m 2 ; intervention). Prednisone was tapered in both groups after 1 month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m 2 per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome). We followed participants for $1 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6-13.5 years]) were enrolled and followed for #60 months (median, 22 months). Three-month proteinuria was 42% lower in the rituximab group (geometric mean ratio, 0.58; 95% confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6 months; median time to relapse in the rituximab group was 18 months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS.

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Section: Discussionmentioning

confidence: 99%

Rituximab in Children with Steroid-Dependent Nephrotic Syndrome

Ravani

Rossi

Bonanni

et al. 2015

Journal of the American Society of Nephrology

161

142

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“…The mechanisms of action of RTX to treat ITP remain speculative, although the removal of autoreactive B-cells is likely to play an important role. Additional mechanisms of action have been proposed, including the indirect modulation of T-cell homeostasis [7]. Three noncontrolled studies have reported the efficacy of RTX given at lower doses (100 mg every week for 4 weeks), and have shown good short-term response rates [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of rituximab given at 1,000 mg on days 1 and 15 compared to the standard regimen to treat adult immune thrombocytopenia

Mahévas

Ebbo

Audia³

et al. 2013

American J Hematol

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Rituximab (RTX) is used off-label to treat immune thrombocytopenia (ITP) but the regimen now commonly used in rheumatoid arthritis has not been evaluated in ITP. The aim of this large French multicenter retrospective study was to compare the efficacy and safety of two RTX regimens in adult's ITP. The efficacy of two (RTX) regimens: standard therapy of 375 mg/m 2 weekly for 4 weeks vs. a rheumatoid arthritis (RA) regimen of 1,000 mg on days 1 and 15, to treat ITP was compared. We included adults patients with previously primary ITP treated with RTX instead of treated primary ITP. (CR) was defined as a platelet count >100 3 10 9 /L, and a response (R) by a platelet count of >30 3 10 9 /L with a least a doubling of the baseline value. Of the 107 patients included, 61 (57%) received the standard regimen and 46 (43%) the RA regimen. Baseline characteristics and overall response rates at 3 month (M3) and 12 months (M12) were not significantly different between the groups. At M12, 22/61 patients (36%) treated with the standard regimen and 23/46 (50%) with the RA regimen achieved an overall response (R 1 CR). The initial pattern of response at M3 was associated with a later pattern of response by M12 in both groups. In multivariate analysis, both a younger age and a low number of previous therapies were associated with a higher likelihood of overall response at M12. Tolerance was good and comparable between the two groups. The RA regimen is an effective and safe alternative to the standard regimen to treat adults with ITP. Am. J. Hematol. 88:858-861,

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“…1 The autoantibodies produced by autoreactive B cells against self-antigens, specifically immunoglobulin G (IgG) antibodies against glycoprotein IIb (GPIIb)/IIIa and/or GPIb/IX, are considered to play a crucial role. 2 In addition, several abnormalities involving the cellular mechanisms of immune modulation, such as the T helper 1 (Th1) bias, 3,4 the decreased number or defective suppressive function of regulatory T cells, [5][6][7] and the platelet destruction by cytotoxic T cells (CTLs), [8][9][10] have been described. The cause for these abnormalities remains unknown.…”

Section: Introductionmentioning

confidence: 99%

The effects of BAFF and BAFF-R-Fc fusion protein in immune thrombocytopenia

Zhu

Shi

Peng

et al. 2009

Blood

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IntroductionImmune thrombocytopenia (ITP) is an autoimmune disorder in which the patient's immune system is activated by platelet autoantigens resulting in immune-mediated platelet destruction and/or suppression of platelet production. 1 The autoantibodies produced by autoreactive B cells against self-antigens, specifically immunoglobulin G (IgG) antibodies against glycoprotein IIb (GPIIb)/IIIa and/or GPIb/IX, are considered to play a crucial role. 2 In addition, several abnormalities involving the cellular mechanisms of immune modulation, such as the T helper 1 (Th1) bias, 3,4 the decreased number or defective suppressive function of regulatory T cells, 5-7 and the platelet destruction by cytotoxic T cells (CTLs), [8][9][10] have been described. The cause for these abnormalities remains unknown. Moreover, the treatment regimens for ITP including glucorticosteroids, intravenous immunoglobulin G, anti-D, and splenectomy are not always effective, and only one-third of adult patients achieve long-term remission.B-cell activating factor (BAFF; also known as B-lymphocyte stimulator, tumor necrosis factor and apoptosis ligand-related leukocyte-expressed ligand 1, tumor necrosis factor homologue that activates apoptosis, nuclear factor B, and c-Jun NH 2 -terminal kinase, and tumor necrosis factor superfamily 13B) belonging to the family of tumor necrosis factor (TNF) ligands is critical for the maintenance of normal B-cell development, homeostasis, and autoreactivity 11,12 and T-cell costimulation. [13][14][15] In addition, BAFF also augments certain Th1-associated inflammatory responses. 16 BAFF binds to 3 receptors: B-cell maturation antigen (tumor necrosis factor receptor superfamily, member 17 [TNFRSF17]), transmembrane activator and calcium-modulating cyclophilin ligand (CAML) interactor (TACI; TNFRSF13B), and BAFF receptor (BR3/BAFF-R; TNFRSF13C). 17,18 BR3, identified as the crucial receptor for B-cell survival, is expressed on a wide range of B-cell subsets, including immature, transitional, mature, memory, and germinal center B cells, as well as on plasma cells. 19 Furthermore, BAFF binding to BR3 on T cells has been shown to costimulate T-cell proliferation both in vitro and in vivo. 15 Several lines of evidence suggested that BAFF may play an important role in autoimmunity. Autoantigen-binding B cells may have an increased dependence on the BAFF survival signal. 20 In addition, elevated BAFF plasma level was observed in many patients with autoimmune diseases such as rheumatoid arthritis (RA), 21 systemic lupus erythematosus (SLE), 22 Sjögren syndrome (SS), 23 and multiple sclerosis. 24 Inhibition of BAFF signaling is a potentially therapeutic option for treatment of B cell-mediated autoimmune conditions. Data from animal tests and clinical trials had proved that blockade of BAFF by blocking reagents (TACI-Ig, BAFF-R-Ig, BR3-Fc) was an effective therapeutic approach for some autoimmune diseases. [25][26][27] In our study, we focused on the effects of BAFF and BR3-Fc in ITP, and found recombinant human BAFF (r...

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Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell–depleting therapy with rituximab

Cited by 368 publications

References 16 publications

Rituximab in Children with Steroid-Dependent Nephrotic Syndrome

Rituximab in Children with Steroid-Dependent Nephrotic Syndrome

Efficacy and safety of rituximab given at 1,000 mg on days 1 and 15 compared to the standard regimen to treat adult immune thrombocytopenia

The effects of BAFF and BAFF-R-Fc fusion protein in immune thrombocytopenia

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