Evidence map›Paper›PMID 31829278›Full record

ArticleArthritis research & therapy2019

Activation of natural killer cells by rituximab in granulomatosis with polyangiitis.

Doris Urlaub, Shuyang Zhao, Norbert Blank, Raoul Bergner, Maren Claus, Theresa Tretter, Hanns-Martin Lorenz, Carsten Watzl, Wolfgang Merkt

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arthritis research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.8field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Doris UrlaubLeibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Dortmund, Germany.
Shuyang ZhaoDepartment of Hematology, Oncology and Rheumatology, Internal Medicine V, University Hospital of Heidelberg, Heidelberg, Germany.
Norbert BlankDepartment of Hematology, Oncology and Rheumatology, Internal Medicine V, University Hospital of Heidelberg, Heidelberg, Germany.
Raoul BergnerDepartment of Rheumatology, Nephrology, Oncology, Klinikum Ludwigshafen, Ludwigshafen, Germany.
Maren ClausLeibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Dortmund, Germany.
Theresa TretterDepartment of Hematology, Oncology and Rheumatology, Internal Medicine V, University Hospital of Heidelberg, Heidelberg, Germany.
Hanns-Martin LorenzDepartment of Hematology, Oncology and Rheumatology, Internal Medicine V, University Hospital of Heidelberg, Heidelberg, Germany.
Carsten WatzlLeibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Dortmund, Germany.
Wolfgang MerktDepartment of Hematology, Oncology and Rheumatology, Internal Medicine V, University Hospital of Heidelberg, Heidelberg, Germany. wolfgang.merkt@med.uni-heidelberg.de.ORCID 0000-0002-3108-154X
Heidelberg University · DETU Dortmund University · DEKlinikum Ludwigshafen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveIn the last few years, anti-CD20 antibody rituximab profoundly changed the therapeutic landscape of granulomatosis with polyangiitis (GPA). Here, we investigated whether natural killer (NK) cells may play a role in rituximab's mechanism of action in GPA.

methodsB cell depletion, NK cell degranulation, and the expression of CD69 and CD16 on NK cells were measured in a series of in vitro experiments using peripheral blood mononuclear cells (PBMCs). In vivo activation of NK cells was investigated in patients receiving rituximab infusions. Cells were analyzed by seven-color flow cytometry.

resultsNK cells from GPA patients were activated by immobilized rituximab. Also soluble rituximab activated NK cells, provided that B cells were present. NK cells degranulated and expressed the activation marker CD69 while CD16 expression was decreased. This activation of NK cells by soluble rituximab was accompanied by a reduction of B cells. The next-generation anti-CD20 antibody obinutuzumab showed stronger effects compared to rituximab on both the reduction of B cells and the activation of NK cells. Finally, we found that rituximab led to the activation of NK cells in vivo, provided that B cells were not depleted due to prior rituximab infusions.

conclusionB cell-bound rituximab activates NK cells in GPA. While NK cells therefore participate in rituximab's mechanism of action in humans, their potential may be more efficiently exploited, e.g., by Fc engineering of therapeutic antibodies.

Indexed as

Granulomatosis with PolyangiitisHumansImmunologic FactorsKiller Cells, NaturalLymphocyte ActivationRituximabImmunologic FactorsRituximabANCA-associated vasculitisAntibody-dependent cellular cytotoxicity (ADCC)B cell depletionFc-γ-receptor IIIa (FcγRIIIa; CD16)Granulomatosis with polyangiitisNatural killer cellsObinutuzumabRheumatic diseasesRituximab

Identifiers

PMID31829278
PMCPMC6907269
OpenAlexW2996347204

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.