Changes in peripheral blood lymphocyte subsets during arthritis development in arthralgia patients

Lubbers, Joyce M.; Beers-Tas, Marian H. van; Vosslamber, Saskia; Türk, S.; Ridder, Sander de; Mantel, Elise; Wesseling, John G.; Reijm, Martine; Hoogstraten, Ingrid M. van; Bijlsma, J. W. J.; Schaardenburg, Dirkjan van; Bontkes, Hetty J.; Verweij, Cornelis L.

doi:10.1186/s13075-016-1102-2

Cited by 27 publications

(20 citation statements)

References 21 publications

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“… 49 Seropositive patients who developed arthritis had a significantly decreased number of peripheral CD8+ T cells and memory B cells compared with non-converters. 50 B cell subtypes have been studied; patients with seropositive arthralgia with a low B cell score, measured as expression of CD19, CD20, CD79α and CD79β, had an increased risk of arthritis if there was also a high type I interferon signature. 51 B cell receptor (BCR) clones, defined as BCR clones expanded beyond 0.5% of the total repertoire, have also been studied in the peripheral blood of 71 seropositive individuals at risk of RA and were associated with an enhanced risk of arthritis.…”

Section: Markers Characterising Immune Cell Dysfunctionmentioning

confidence: 99%

Which patients presenting with arthralgia eventually develop rheumatoid arthritis? The current state of the art

2017

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Early initiation of treatment in patients with inflammatory arthritis at risk of persistence and/or erosive progression is important because it is associated with a reduced rate of progression of joint damage and functional disability. It has been proposed that a window of opportunity exists, during which disease processes are less matured and disease modification can be more effective. The phase of arthralgia preceding clinical arthritis is likely to be an important part of this window of opportunity, during which treatment might prevent progression to clinical arthritis. Several proof-of-concept trials in individuals with arthralgia are now evaluating this hypothesis. Central to such trials is the ability to identify groups at high risk of rheumatoid arthritis (RA) in whom preventive treatment can be tested. This review describes the relevance of adequate prediction making, as well as the accuracy of different types of predictors (including imaging and serological markers) with their value in predicting the progression of arthralgia to arthritis. Despite promising results, studies have been performed in heterogeneous patient populations and most findings have not been validated in independent studies. Future observational or preventive studies should be conducted with homogeneous patient groups (eg, patients fulfilling the European League Against Rheumatism criteria for arthralgia at risk of RA) in order to increase interstudy comparability and to allow result validation.

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Section: Markers Characterising Immune Cell Dysfunctionmentioning

confidence: 99%

Which patients presenting with arthralgia eventually develop rheumatoid arthritis? The current state of the art

2017

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“…В исследовании J. Lü bbers и соавт. [22] обнаружено снижение уровней CD27+ B-клеток памяти и активированных CD80+ B-клеток у 89 пациентов с ранним нелеченым РА по сравнению с донорами (n=37). В работе P. Roll и соавт.…”

Section: Discussionunclassified

B-lymphocyte subpopulations in patients with rheumatoid arthritis and the effect of an interleukin-6 receptor inhibitor on them.

Gerasimova¹,

Попкова²,

Алексанкин³

et al. 2019

Naučno-praktičeskaâ revmatologiâ

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The clinical efficacy and safety of interleukin-6 (IL-6) receptor blockade have been well studied, but the data on the impact of therapeutic inhibition of IL-6 on B cells are scarce and contradictory. Preliminary reports have shown that B cell function and a humoral immune response may be modulated by an IL-6 receptor inhibitor.Objective: to assess the effect of 12-month tocilizumab (TCZ) therapy on B-cell phenotype and gene expression in RA and to analyze the association between B-cell subsets and RA activity.Subjects and methods. Examinations were made in 24 active RA patients (20 women and 4 men) (median age, 55 [49; 64] years; disease duration, 72 [24; 108] months; DAS28 5.8 [5.3; 6.3]; the patients were seropositive for rheumatoid factor (RF) (100%) and for anti-cyclic citrullinated peptide antibodies (87.3%). The patients received TCZ 8 mg/kg every 4 weeks. After 12 months of therapy, 54% of patients were categorized as good responders, 46% as moderate responders according to the EULAR response criteria. A control group consisted of 29 volunteers (21 women and 8 men; median age, 58.5 [53.0; 62.0] years). Peripheral blood lymphocytes were immunophenotyped at the time of enrollment and after 12 months. The absolute and relative counts of CD19+B lymphocytes, memory B cells (CD19+CD27+), non-switched memory B cells (CD19+IgD+CD27+), switched memory B cells (CD19+IgDCD27+), naive (CD19+IgD+CD27-), double-negative (CD19+IgD-CD27-), transitional (CD19+IgD+CD10+CD38++CD27) B cells, plasma cells (CD19+СD38+), and plasmablasts (CD19+СD38+++IgD-CD27+CD20-) were estimated using multicolor flow cytometry. Results and discussion. The relative and absolute counts of memory B cells (CD19+CD27+) (1.3 [0.9; 1.7]%, 0015 [0.001; 0.003]•109/l), switched memory B cells (CD19+IgD-CD27+) (6.8 [3.6; 11.6]%, 0.01 [0.005; 0.02]•109/l), and the absolute number of transitional B cells (CD19+CD38++CD10+IgD+CD27-) (0.00009 [0; 0.00028]•109/l) were found to be lower in RA patients than in donors: 2.2 [1.1; 3.0]%, 0.003 [0.001; 0.007]•109/l; 12.8 [9.3; 17.0]%, 0.02 [0.01; 0.04]•109/l; 0.0001 [0; 0.0003]•109/l, respectively (p<0.05 for all cases). After 12 months of TCZ therapy initiation, there were decreases in the relative and absolute counts of plasmablasts (CD19+CD38+++CD27+IgD-CD20-) from 0.15 [0.1; 0.3] to 0.1 [0.01; 0.1]% and from 0.0003 [0.00007; 0.004]•109/l to 0.0001 [0; 0.0003]•109/l, respectively (p<0.05). At the same time, the relative and absolute counts of memory B cells (CD19+CD27+) and switched memory B cells (CD19+CD27+IgD-) remained lower in RA patients than in donors: 1.0 [0.7; 1.2] and 2.2 [1.1; 3.0]%; 0.001 [0.006; 0.003]•109/l and 0.003 [0.001; 0.007]•109/l; 3.1 [1.1; 4.2] and 12.8 [9.3; 17.0]%; 0.003 [0.002; 0.006]•109/l and 0.02 [0.01; 0.04]•109/l, respectively (p<0.05 for all cases). Following 12 months of TCZ therapy, the numbers of other B-cell subpopulations were not considerably altered. When included in the study, the patients with RA showed correlations between the absolute count of memory B cells (CD19+CD27+) and the level of C-reactive protein (r=0.50; p<0.05); between the absolute count of plasmablasts (CD19+CD38+++CD27+IgD-CD20-) and the level of RF (r=0.41 and r=0.52; p<0.05). There were no correlations of B cell subsets with clinical and laboratory findings after 12 months of TCZ initiation.Conclusion. Immunophenotyping of peripheral blood B lymphocyte subsets showed the lower relative and absolute counts of memory B cells (CD19+CD27+) and switched memory B cells (CD19+CD27+IgD-) in RA patients than in healthy donors. The found correlations between the counts of memory B cells and plasmablasts and the values of laboratory parameters in patients with high RA activity may suggest that B lymphocytes are involved in the pathogenesis of RA. There was a decline in plasmablast levels after 12 months of TCZ therapy.

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“… 14 15 The number of CD27 + memory B cells is decreased in patients with seropositive arthralgia who converted to patients with RA compared with non-converters. 11 This decrease was reported in patients with arthralgia who developed RA within 12 months but not in those who converted at a later time point.…”

Section: Introductionmentioning

confidence: 93%

“…A study comparing patients with seropositive arthralgia who converted to patients with RA with non-converters showed decreased CD8 + cytotoxic T cells approximately 24 months prior to arthritis development. 11 The CD8 + cytotoxic T cells described in the article are determined by CD3 and CD8 positivity and represent a rather diverse group. Not all CD8 + T cells have the same ability to be cytotoxic.…”

Section: Introductionmentioning

confidence: 99%

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From patients with arthralgia, pre-RA and recently diagnosed RA: what is the current status of understanding RA pathogenesis?

2018

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It is believed that therapy for rheumatoid arthritis (RA) is the most effective and beneficial within a short time frame around RA diagnosis. This insight has caused a shift from research in patients with established RA to patients at risk of developing RA and recently diagnosed patients. It is important for improvement of RA therapy to understand when and what changes occur in patients developing RA. This is true for both seropositive and seronegative patients. Activation of the immune system as presented by autoantibodies, increased cytokine and chemokine production, and alterations within several immune cells occur during RA development. In this review we describe RA pathogenesis with a focus on knowledge obtained from patients with arthralgia, pre-RA and recently diagnosed RA. Connections are proposed between altered immune cells, cytokines and chemokines, and events like synovial hyperplasia, pain and bone damage.

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Changes in peripheral blood lymphocyte subsets during arthritis development in arthralgia patients

Cited by 27 publications

References 21 publications

Which patients presenting with arthralgia eventually develop rheumatoid arthritis? The current state of the art

Which patients presenting with arthralgia eventually develop rheumatoid arthritis? The current state of the art

B-lymphocyte subpopulations in patients with rheumatoid arthritis and the effect of an interleukin-6 receptor inhibitor on them.

From patients with arthralgia, pre-RA and recently diagnosed RA: what is the current status of understanding RA pathogenesis?

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