Anti-CD20 therapy in patients with rheumatoid arthritis: Predictors of response and B cell subset regeneration after repeated treatment

2008 ◽  
Vol 58 (6) ◽  
pp. 1566-1575 ◽  
Author(s):  
Petra Roll ◽  
Thomas Dörner ◽  
Hans-Peter Tony
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cell ◽  
Cell Subset ◽  
Repeated Treatment ◽  
Predictors Of Response ◽  
Anti Cd20

A2.18 Induction and characterisation of the dominant IL-10 producing B cell subset in healthy blood donors and rheumatoid arthritis patients

2016 ◽  
Vol 75 (Suppl 1) ◽  
pp. A22.2-A22
Author(s):  
ZS Bankó ◽  
J Pozsgay ◽  
M Tóth ◽  
T Gáti ◽  
G Nagy ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cell ◽  
Blood Donors ◽  
Cell Subset

scholarly journals CyTOF-Enabled Analysis Identifies Class-Switched B Cells as the Main Lymphocyte Subset Associated With Disease Relapse in Children With Idiopathic Nephrotic Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Miguel Fribourg ◽  
Michela Cioni ◽  
GianMarco Ghiggeri ◽  
Chiara Cantarelli ◽  
Jeremy S. Leventhal ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
B Cells ◽  
B Cell ◽  
Immune Cell ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Disease Relapse ◽  
Steroid Dependent ◽  
Cellular Markers ◽  
Anti Cd20

B cell depleting therapies permit immunosuppressive drug withdrawal and maintain remission in patients with frequently relapsing nephrotic syndrome (FRNS) or steroid–dependent nephrotic syndrome (SDNS), but lack of biomarkers for treatment failure. Post-depletion immune cell reconstitution may identify relapsing patients, but previous characterizations suffered from methodological limitations of flow cytometry. Time-of-flight mass cytometry (CyTOF) is a comprehensive analytic modality that simultaneously quantifies over 40 cellular markers. Herein, we report CyTOF-enabled immune cell comparisons over a 12-month period from 30 children with SDNS receiving B cell depleting therapy who either relapsed (n = 17) or remained stable (n = 13). Anti-CD20 treatment depleted all B cells subsets and CD20 depleting agent choice (rituximab vs ofatumumab) did not affect B cell subset recovery. Despite equal total numbers of B cells, 5 subsets of B cells were significantly higher in relapsing individuals; all identified subsets of B cells were class-switched. T cell subsets (including T follicular helper cells and regulatory T cells) and other major immune compartments were largely unaffected by B cell depletion, and similar between relapsing and stable children. In conclusion, CyTOF analysis of immune cells from anti-CD20 antibody treated patients identifies class-switched B cells as the main subset whose expansion associates with disease relapse. Our findings set the basis for future studies exploring how identified subsets can be used to monitor treatment response and improve our understanding of the pathogenesis of the disease.

scholarly journals Multiple Myeloma Includes Phenotypically Defined Subsets of Clonotypic CD20+ B Cells that Persist during Treatment with Rituximab

2008 ◽  
Vol 2 ◽  
pp. CMO.S615 ◽  
Author(s):  
Linda M. Pilarski ◽  
Eva Baigorri ◽  
Michael J. Mant ◽  
Patrick M. Pilarski ◽  
Penelope Adamson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cells ◽  
B Cell ◽  
Plasma Cells ◽  
Cell Subset ◽  
Light Scatter ◽  
Cell Compartments ◽  
B Lineage ◽  
B Cell Subsets ◽  
Anti Cd20

Potential progenitor B cell compartments in multiple myeloma (MM) are clinically important. MM B cells and some circulating MM plasma cells express CD20, predicting their clearance by treatment with anti-CD20. Here we describe two types of clonotypic CD20+ B cell in peripheral blood of myeloma patients, identified by their expression of CD19 and CD20 epitopes, their expression of CD45RA and their light scatter properties. Thus, the circulating component of the MM clone includes at least two distinct CD19+ CD20+ B cell compartments, as well as CD138+CD20+ plasma cells. To determine whether either or both B cell subsets and the CD20+ plasma cell subset were depleted by anti-CD20 therapy, they were evaluated before, during and after treatment of patients with rituximab (anti-CD20), followed by quantifying B cell subsets over a 5 month period during and after treatment. Overall, all three types of circulating B lineage cells persist despite treatment with rituximab. The inability of rituximab to prolong survival in MM may result from this failure to deplete CD20+ B and plasma cells in MM.

scholarly journals Frequency of Regulatory T Cells is Not Affected by Transient B Cell Depletion Using Anti-CD20 Antibodies in Rheumatoid Arthritis

2009 ◽  
Vol 2 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Martin Feuchtenberger ◽  
Sabine Muller ◽  
Petra Roll ◽  
Anne Waschbisch ◽  
Arne Schafer ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Anti Cd20 ◽  
Cd20 Antibodies

scholarly journals Natural killer-like B cells promote Th17 cell differentiation and exacerbate rheumatoid arthritis

2021 ◽  
Author(s):  
Ping Wang ◽  
Jing Song ◽  
Mingxin Bai ◽  
Xi Zheng ◽  
Yang Xie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Disease Progression ◽  
Natural Killer ◽  
Th17 Cell ◽  
Cell Subset ◽  
Th17 Cell Differentiation

B cells are important participants in the pathogenesis of rheumatoid arthritis (RA). Besides classical B cells, novel B cell subsets are continually to be identified in recent years. Natural killer-like B (NKB) cells, a newly recognized B cell subset, are proved to be actively involved in the anti-infection immunity. However, their role in RA and the potential mechanism remain elusive. Here, we showed that NKB cells were expanded dramatically in collagen-induced arthritis (CIA) mice, demonstrating dynamic changes during the disease progression. These cells promoted CD4+ effector T cell proliferation and Th17 cell differentiation in vitro, while adoptive transfer of these cells exacerbated the arthritis severity of CIA mice. RNA Sequencing revealed that NKB cells displayed distinct differential gene expression profile under RA circumstance, potential perpetuating the disease progression. Moreover, the frequencies of NKB cells were significantly increased in RA patients, positively correlated with the clinical and immunological features. After effective therapy, these cells could be recovered to normal levels. Taken together, our results preliminarily revealed the pathogenic role of NKB cells in RA by promoting Th17 proinflammatory responses. Targeting these cells might provide potential therapeutic strategies for this persistent disease.

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

2006 ◽  
Vol 54 (8) ◽  
pp. 2377-2386 ◽  
Author(s):  
Petra Roll ◽  
Arumugam Palanichamy ◽  
Christian Kneitz ◽  
Thomas Dorner ◽  
Hans-Peter Tony
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cell ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
B Cell Subsets ◽  
Anti Cd20 ◽  
Cd20 Antibodies

scholarly journals Decrease in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity

2010 ◽  
Vol 69 (12) ◽  
pp. 2137-2144 ◽  
Author(s):  
T Groot Kormelink ◽  
J Tekstra ◽  
R M Thurlings ◽  
M H J Boumans ◽  
K Vos ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
B Cell ◽  
Light Chains ◽  
Free Light Chains ◽  
Reactive Protein ◽  
Patient Groups ◽  
Effect Of Treatment ◽  
Anti Cd20 ◽  
Relationship Of

ObjectivesImmunoglobulin (Ig) free light chains (FLCs) are short-lived B cell products that contribute to inflammation in several experimental disease models. In this study, FLC concentrations in inflamed joints of patients with rheumatoid arthritis (RA) as compared to patients with osteoarthritis were investigated. In addition, the relationship of FLCs and disease activity upon B cell depletion (rituximab) in patients with RA was studied.MethodsSynovial fluid (SF) and tissue from patients with RA were analysed for local presence of FLCs using ELISA and immunohistochemistry. In addition, FLC concentrations were measured (at baseline, 3 and 6 months after treatment) in 50 patients with RA with active disease who were treated with rituximab. Changes in FLCs were correlated to changes in disease activity and compared to alterations in IgM, IgG, IgA, IgM-rheumatoid factor (RF) and IgG-anti-citrullinated protein antibody (ACPA) concentrations.ResultsFLCs were detected in synovial tissue from patients with RA, and high FLC concentrations were found in SF from inflamed joints, which positively correlate with serum FLC concentrations. Serum FLC concentrations significantly correlated with disease activity score using 28 joint counts, erythrocyte sedimentation rate (ESR) and C reactive protein, and changes in FLC correlated with clinical improvement after rituximab treatment. Moreover, effect of treatment on FLC concentrations discriminated clinical responders from non-responders, whereas IgM-RF and IgG-ACPA significantly decreased in both patient groups.ConclusionsFLCs are abundantly present in inflamed joints and FLC levels correlate with disease activity. The correlation of FLC concentrations and disease activity indicates that FLCs may be relevant biomarkers for treatment response to rituximab in patients with RA and suggests that targeting FLC may be of importance in the therapy of RA.

scholarly journals Rheumatoid arthritis patients express a skewed repertoire of polyclonal, hypomutated B-cell receptors

2019 ◽  
Author(s):  
Graeme J.M. Cowan ◽  
Katherine Miles ◽  
Lorenzo Capitani ◽  
Sophie S.B. Giguere ◽  
Hanna Johnsson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Critical Role ◽  
Cell Subset ◽  
Antigen Receptors ◽  
Cell Repertoire ◽  
Variable Heavy ◽  
Polyclonal Igg

AbstractObjectivesThe success of B cell depletion therapy in rheumatoid arthritis (RA) therapy testifies to their importance in disease pathogenesis, but the precise B cells mediating this are unclear. For example, it is unknown if RA patients predominantly express a limited number of circulating clonally expanded populations of B cells with highly mutated B cell antigen receptors (BCRs) that would constitute a shared antigen driven response.MethodsTo address this, we have undertaken the largest study to date utilising next generation sequencing (NGS), to identify the full length of the peripheral blood BCR sequences from the antigen-binding heavy chain. Between 25,000 to 200,000 BCR sequences per patient were analysed from 127 newly diagnosed RA patients, 16 heathy controls, 16 RA patients with established disease and 8 paired blood and synovial samples. This was complemented with B cell subset analysis from an additional 64 RA patients and 22 healthy controls.ResultsRA patients expressed a significantly higher percentage of circulating poorly mutated polyclonal IgG+ve variable heavy (IgG-Vh) BCR sequences, both at the time of diagnosis and following treatment. These sequences resided predominantly within TNF-alpha secreting IgG+veCD27−ve B cells, that were expanded in RA peripheral blood and enriched in the rheumatoid synovium. Surprisingly, peripheral and synovial B cell repertoires of RA patients are quite distinct, sharing very few IgG sequences.ConclusionsThis is the first report to conclusively establish that a substantial component of the peripheral B cell repertoire in RA consists of polyclonal hypomutated IgG+ve BCRs that may play a critical role in driving an autoimmune mediated inflammation.

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