Regeneration of B cell subsets after transient B cell depletion using anti‐CD20 antibodies in rheumatoid arthritis

Roll, Petra; Palanichamy, Arumugam; Kneitz, Christian; Dörner, Thomas; Tony, Hans‐Peter

doi:10.1002/art.22019

Cited by 293 publications

(255 citation statements)

References 36 publications

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“…It is becoming increasingly clear that rituximab treatment does not merely result in transient B cell depletion, but has a distinct long-term impact on immunologic homeostasis, including distinct B cell subpopulations, which we are just beginning to understand. The peripheral repopulation of B cell subpopulations follows a characteristic pattern that seems to recapitulate B cell ontogeny, with high numbers of transitional B cells early on, followed by B cells with a mainly naive phenotype (7,24,29,31). Although peripheral B cell numbers normalize in most patients between 1 and 2 years after a single course of antibody treatment, a long-term reduction in memory B cells, particularly of the IgDϩIgMϩ memory compartment, has been observed (7).…”

Section: Discussionmentioning

confidence: 99%

“…Long-term reduction of memory B cells after rituximab treatment is not specific to RA (7). It has been shown in various diseases, including SLE (31) and non-Hodgkin's lymphoma (40).…”

Section: Discussionmentioning

confidence: 99%

“…IgDϩ memory B cells repopulate slowly during rituximab-mediated B cell depletion (7). Whereas the overall B cell count of CD19ϩ B cells is normalized 2 years after rituximab treatment, IgDϩCD27ϩ B cells still make up 2.76 Ϯ 0.3% of the total CD19ϩ B cell population (mean Ϯ SEM) 6 years after treatment with rituximab, which equals an ϳ70% ongoing reduction.…”

Section: H 3 Gene Rearrangements In Single Cells Show a Diversifiedmentioning

confidence: 99%

“…In addition, there is evidence of a shift in the expressed B cell repertoire of specific antigen receptors during the course of chronic autoimmune disease. Disturbances in B cell receptor editing and central or peripheral tolerance machinery additionally contribute to abnormal B cell activation and proliferation (7)(8)(9). Therefore, "resetting" the immune system by temporal B cell depletion seems to be an interesting goal.…”

mentioning

confidence: 99%

“…The influence on memory B cells is of particular interest. Particularly, IgDϩCD27ϩ memory B cells are quantitatively diminished for Ͼ2 years after a single course of rituximab (7).…”

mentioning

confidence: 99%

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Delayed acquisition of somatic hypermutations in repopulated IGD+CD27+ memory B cell receptors after rituximab treatment

Muhammad¹,

Roll²,

Einsele³

et al. 2009

Arthritis & Rheumatism

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Section: Discussionmentioning

confidence: 99%

“…Long-term reduction of memory B cells after rituximab treatment is not specific to RA (7). It has been shown in various diseases, including SLE (31) and non-Hodgkin's lymphoma (40).…”

Section: Discussionmentioning

confidence: 99%

Section: H 3 Gene Rearrangements In Single Cells Show a Diversifiedmentioning

confidence: 99%

mentioning

confidence: 99%

“…The influence on memory B cells is of particular interest. Particularly, IgDϩCD27ϩ memory B cells are quantitatively diminished for Ͼ2 years after a single course of rituximab (7).…”

mentioning

confidence: 99%

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Delayed acquisition of somatic hypermutations in repopulated IGD+CD27+ memory B cell receptors after rituximab treatment

Muhammad¹,

Roll²,

Einsele³

et al. 2009

Arthritis & Rheumatism

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Association of Rituximab Use With Adverse Events in Children, Adolescents, and Young Adults

et al. 2021

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IMPORTANCE Rituximab is among the most frequently used immunotherapies in pediatrics. Few studies have reported long-term adverse events associated with its use for children. OBJECTIVE To describe the use of rituximab and to assess whether its use is associated with shortor long-term adverse events, infections, or time to immune reconstitution in a diverse group of young people. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included 468 patients aged younger than 21 years who received rituximab for diverse indications between October 1, 2010, and December 31, 2017, at Texas Children's Hospital, a large pediatric referral hospital. Patterns of adverse events, infections, and immune recovery are described. Data analyses were conducted from December 2019 to June 2020. EXPOSURE One or more doses of rituximab. MAIN OUTCOMES AND MEASURES Adverse drug events (eg, anaphylaxis), incidence of mild and severe infections, and time to recovery of B lymphocyte subset counts and immunoglobulin levels. Survival models and logistic regression analyses and were used to identify associated risk factors of infectious and noninfectious adverse drug events. RESULTS We identified 468 patients receiving at least 1 dose of rituximab. The total follow-up time was 11 713 person-months. Of the 468 patients, 293 (62.6%) were female, the median (interquartile range) age at receipt of dose was 14.3 (9.9-16.8) years, and 209 (44.7%) were self-reported White Hispanic. Adverse events associated with rituximab infusion occurred in 72 patients (15.4%), and anaphylaxis occurred in 17 patients (3.6%). Long-term adverse events, such as prolonged neutropenia and leukoencephalopathy, were absent. Infections occurred in 224 patients (47.9%); 84 patients (17.9%) had severe infections, and 3 patients (0.6%) had lethal infections. Concurrent use of intravenous chemotherapy, treatment of systemic lupus erythematosus, neutropenia, and use of intravenous immunoglobulin were associated with increased risk of infection. Among 135 patients (28.8%) followed up to B cell count recovery, CD19 + or CD20 + cell numbers normalized in a median of 9.0 months (interquartile range, 5.9-14.4 months) following rituximab use; 48 of 95 patients (51%) evaluated beyond a year had low-forage B cell counts. Recovery of CD27 + memory B cell number occurred in a median of 15.7 months (interquartile range, 6.0-22.7 months). Among patients with normal baseline values, low immunoglobulin G (IgG) levels developed in 67 of 289 patients (23.2%) and low IgM levels in 118 of 255 patients (40.8%); of these patients evaluated beyond 12 months from rituximab, 16 of 117 (13.7%) had persistently low IgG and 37 (33.9%) of 109 had persistently low IgM.

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Rituximab for people with multiple sclerosis

Filippini

Kruja

et al. 2021

Cochrane Database of Systematic Reviews

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The main objective is to assess the benefits and harms of rituximab compared to placebo or another DMT for people with multiple sclerosis. Specific comparisons include:• rituximab compared with placebo or other DMTs as first choice treatment for relapsing forms of MS;• rituximab when switching from another DMT compared with placebo or other DMTs for relapsing forms of MS;• rituximab compared with placebo or other DMTs as first choice treatment for progressive forms of MS; and • rituximab when switching from another DMT compared with placebo or other DMTs for progressive forms of MS.

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Regeneration of B cell subsets after transient B cell depletion using anti‐CD20 antibodies in rheumatoid arthritis

Cited by 293 publications

References 36 publications

Delayed acquisition of somatic hypermutations in repopulated IGD+CD27+ memory B cell receptors after rituximab treatment

Delayed acquisition of somatic hypermutations in repopulated IGD+CD27+ memory B cell receptors after rituximab treatment

Association of Rituximab Use With Adverse Events in Children, Adolescents, and Young Adults

Rituximab for people with multiple sclerosis

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