Alterations in peripheral blood memory B cells in patients with active rheumatoid arthritis are dependent on the action of tumour necrosis factor

Souto-Carneiro, Margarida; Mahadevan, Vijayabhanu; Takada, Kazuki; Fritsch-Stork, Ruth; Nanki, Toshihiro; Brown, Margaret R.; Fleisher, Thomas A.; Wilson, Martin; Goldbach‐Mansky, Raphaela; Lipsky, Peter E.

doi:10.1186/ar2718

Cited by 111 publications

(147 citation statements)

References 58 publications

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“…The levels have been reported to be comparable to those in healthy controls (29), but other investigators found a lower frequency of these cells in the periphery (31), particularly in patients with very early RA and a disease duration of less than 6 months (32). Also, anti-TNF␣ therapy seems to be related to increased numbers of preswitch memory B cells (31,33). Due to the limited number of patients in our cohort, we were not able to perform valid subgroup analyses for this.…”

Section: Discussionmentioning

confidence: 73%

In vivo effects of the anti–interleukin‐6 receptor inhibitor tocilizumab on the B cell compartment

Roll¹,

Muhammad²,

M³

et al. 2011

Arthritis & Rheumatism

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Objective. Interleukin-6 (IL-6) receptor inhibition by tocilizumab was recently licensed for the treatment of rheumatoid arthritis (RA). IL-6 induces in vitro differentiation of B cells into antibody-forming cells; however, the in vivo effects of IL-6 inhibition on the B cell compartment are currently not known. The purpose of this study was to examine this feature.Methods. Sixteen patients with active RA were treated in an open-label study with tocilizumab (8 mg/kg every 4 weeks). Immunophenotyping was performed at baseline, week 12, and week 24.Results. Memory B cell subsets declined significantly during tocilizumab therapy. Preswitch memory B cells decreased from a median of 19.6% to 12.3% at week 24 and postswitch memory B cells declined from a median of 18.6% to 15.0% at week 24 (P ‫؍‬ 0.04). In parallel, CD19؉IgA؉ and CD19؉IgG؉ B cells decreased significantly. The proportion of IgA-expressing B cells fell from a median of 9.2% at baseline to 4.3% at week 12 and to 3.6% at week 24 (P ‫؍‬ 0.01). IgG؉ B cells declined from a median of 6.7% at baseline to 4.9% at week 12 (P ‫؍‬ 0.007) and 2.8% at week 24 (P ‫؍‬ 0.01). In parallel, serum levels of IgA and IgG were significantly diminished at week 24 (P < 0.05). There was a good correlation between relative and absolute numbers of IgA؉ B cells with serum IgA at week 24.Conclusion. Tocilizumab induced a significant reduction in the frequency of peripheral preswitch and postswitch memory B cells. In addition, the number of IgG؉ and IgA؉ B cells declined and correlated well with reduced serum immunoglobulin levels. The data indicate that IL-6 blockade affects the B cell hyperreactivity in RA patients.

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Section: Discussionmentioning

confidence: 73%

In vivo effects of the anti–interleukin‐6 receptor inhibitor tocilizumab on the B cell compartment

Roll¹,

Muhammad²,

M³

et al. 2011

Arthritis & Rheumatism

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“…Class‐switched mature memory subsets were enriched in the synovial compartment compared with peripheral blood 111, 112, 113. Switching occurred primarily to IgG and IgA 114.…”

Section: Ramentioning

confidence: 99%

Antibody repertoire analysis in polygenic autoimmune diseases

2018

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SummaryHigh‐throughput sequencing of the DNA/RNA encoding antibody heavy‐ and light‐chains is rapidly transforming the field of adaptive immunity. It can address key questions, including: (i) how the B‐cell repertoire differs in health and disease; and (ii) if it does differ, the point(s) in B‐cell development at which this occurs. The advent of technologies, such as whole‐genome sequencing, offers the chance to link abnormalities in the B‐cell antibody repertoire to specific genomic variants and polymorphisms. Here, we discuss the current research using B‐cell antibody repertoire sequencing in three polygenic autoimmune diseases where there is good evidence for a pathological role for B‐cells, namely systemic lupus erythematosus, multiple sclerosis and rheumatoid arthritis. These autoimmune diseases exhibit significantly skewed B‐cell receptor repertoires compared with healthy controls. Interestingly, some common repertoire defects are shared between diseases, such as elevated IGHV4‐34 gene usage. B‐cell clones have effectively been characterized and tracked between different tissues and blood in autoimmune disease. It has been hypothesized that these differences may signify differences in B‐cell tolerance; however, the mechanisms and implications of these defects are not clear.

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“…This suggests that antigen stimulation may promote the redistribution of naive B cells from lymph tissues to circulation. Souto-Carneiro et al [28] found that the percentages of circulating preswitch CD19 …”

Section: Cd27mentioning

confidence: 99%

High frequencies of activated B cells and T follicular helper cells are correlated with disease activity in patients with new-onset rheumatoid arthritis

Wang

Shan

Jiang

et al. 2013

Clinical and Experimental Immunology

168

166

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Alterations in peripheral blood memory B cells in patients with active rheumatoid arthritis are dependent on the action of tumour necrosis factor

Cited by 111 publications

References 58 publications

In vivo effects of the anti–interleukin‐6 receptor inhibitor tocilizumab on the B cell compartment

In vivo effects of the anti–interleukin‐6 receptor inhibitor tocilizumab on the B cell compartment

Antibody repertoire analysis in polygenic autoimmune diseases

High frequencies of activated B cells and T follicular helper cells are correlated with disease activity in patients with new-onset rheumatoid arthritis

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