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Highly Sensitive Flow Cytometric Detection of Residual B-Cells After Rituximab in Anti-Neutrophil Cytoplasmic Antibodies-Associated Vasculitis Patients

Overview of attention for article published in Frontiers in immunology, December 2020
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (79th percentile)
  • High Attention Score compared to outputs of the same age and source (81st percentile)

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11 X users

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35 Mendeley
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Title
Highly Sensitive Flow Cytometric Detection of Residual B-Cells After Rituximab in Anti-Neutrophil Cytoplasmic Antibodies-Associated Vasculitis Patients
Published in
Frontiers in immunology, December 2020
DOI 10.3389/fimmu.2020.566732
Pubmed ID
Authors

Laura S. van Dam, Jelle M. Oskam, Sylvia W. A. Kamerling, Eline J. Arends, O. W. Bredewold, Magdalena A. Berkowska, Jacques J. M. van Dongen, Ton J. Rabelink, Cees van Kooten, Y. K. Onno Teng

Abstract

B-cell depletion with rituximab (RTX) is an effective treatment for anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients. Nevertheless, relapses are frequent after RTX, often preceded by B-cell repopulation suggesting that residual autoreactive B-cells persist despite therapy. Therefore, this study aimed to identify minimal residual autoimmunity (MRA) in the B-cell compartment of AAV patients treated with RTX. EuroFlow-based highly-sensitive flow cytometry (HSFC) was employed to study B-cell and plasma cell (PC) subsets in-depth in AAV patients before and after RTX treatment. Additionally, peripheral blood mononuclear cells (PBMCs) of these RTX-treated AAV patients were cultured and in vitro stimulated with CpG, IL-2, and IL-21 to induce antibody-secreting cells (ASC). (ANCA)-IgG was measured in these supernatants by ELISA. By employing EuroFlow-based HSFC, we detected circulating CD19+ B-cells at all timepoints after RTX treatment, in contrast to conventional low-sensitive flow cytometry. Pre-germinal center (Pre-GC) B-cells, memory B-cells and CD20+CD138- plasmablasts (PBs) were rapidly and strongly reduced, while CD20-CD138- PrePC and CD20-CD138+ mature (m)PCs were reduced slower and remained detectable. Both memory B-cells and CD20- PCs remained detectable after RTX. Serum ANCA-IgG decreased significantly upon RTX. Changes in ANCA levels strongly correlated with changes in naive, switched CD27+ and CD27- (double-negative) memory B-cells, but not with plasma cells. Lastly, we demonstrated in vitro ANCA production by AAV PBMCs, 24 and 48 weeks after RTX treatment reflecting MRA in the memory compartment of AAV patients. We demonstrated that RTX induced strong reductions in circulating B-cells, but never resulted in complete B-cell depletion. Despite strongly reduced B-cell numbers after RTX, ANCA-specific memory B-cells were still detectable in AAV patients. Thus, MRA is identifiable in AAV and can provide a potential novel approach in personalizing RTX treatment in AAV patients.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 35 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 35 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 14%
Researcher 4 11%
Student > Doctoral Student 3 9%
Student > Ph. D. Student 2 6%
Other 1 3%
Other 5 14%
Unknown 15 43%
Readers by discipline Count As %
Medicine and Dentistry 9 26%
Biochemistry, Genetics and Molecular Biology 3 9%
Psychology 2 6%
Neuroscience 2 6%
Social Sciences 1 3%
Other 1 3%
Unknown 17 49%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 January 2021.
All research outputs
#4,463,760
of 26,314,361 outputs
Outputs from Frontiers in immunology
#4,912
of 32,941 outputs
Outputs of similar age
#111,644
of 533,064 outputs
Outputs of similar age from Frontiers in immunology
#137
of 723 outputs
Altmetric has tracked 26,314,361 research outputs across all sources so far. Compared to these this one has done well and is in the 83rd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 32,941 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.6. This one has done well, scoring higher than 85% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 533,064 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 79% of its contemporaries.
We're also able to compare this research output to 723 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 81% of its contemporaries.