Evidence map›Paper›PMID 35831338›Full record

ArticleScientific reports2022

Integrated single cell and spatial transcriptomics reveal autoreactive differentiated B cells in joints of early rheumatoid arthritis.

Uta Hardt, Konstantin Carlberg, Erik Af Klint, Peter Sahlström, Ludvig Larsson, Annika van Vollenhoven, Susana Hernandez Machado, Lena Israelsson, Khaled Amara, Karine Chemin and 6 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

30 citing papers in PubMed, 43 citations in OpenAlex.

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  8. Spatial transcriptomic applications in orthopedics.Connective tissue research · 2025
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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

16 authors at 5 institutions in 2 countries.

Uta Hardt *Division of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. uta.hardt@ki.se.
Konstantin Carlberg *Department of Gene Technology, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
Erik Af KlintDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Peter SahlströmDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Ludvig LarssonDepartment of Gene Technology, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
Annika van VollenhovenDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Susana Hernandez MachadoDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Lena IsraelssonDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Khaled AmaraDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Karine CheminDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Marina KorotkovaDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Gunilla B Karlsson HedestamDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Anca I CatrinaDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Sarah A TeichmannWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Patrik L StåhlDepartment of Gene Technology, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
Vivianne MalmströmDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. vivianne.malmstrom@ki.se.
Karolinska Institutet · SEKarolinska University Hospital · SEKTH Royal Institute of Technology · SEScience for Life Laboratory · SEWellcome Sanger Institute · GB

Funding

European Research Council Advanced Grant 78816
6 · The paper itself

Abstract

B cells play a significant role in established Rheumatoid Arthritis (RA). However, it is unclear to what extent differentiated B cells are present in joint tissue already at the onset of disease. Here, we studied synovial biopsies (n = 8) captured from untreated patients at time of diagnosis. 3414 index-sorted B cells underwent RNA sequencing and paired tissue pieces were subjected to spatial transcriptomics (n = 4). We performed extensive bioinformatics analyses to dissect the local B cell composition. Select plasma cell immunoglobulin sequences were expressed as monoclonal antibodies and tested by ELISA. Memory and plasma cells were found irrespective of autoantibody status of the patients. Double negative memory B cells were prominent, but did not display a distinct transcriptional profile. The tissue architecture implicate both local B cell maturation via T cell help and plasma cell survival niches with a strong CXCL12-CXCR4 axis. The immunoglobulin sequence analyses revealed clonality between the memory B and plasma cell pools further supporting local maturation. One of the plasma cell-derived antibodies displayed citrulline autoreactivity, demonstrating local autoreactive plasma cell differentiation in joint biopsies captured from untreated early RA. Hence, plasma cell niches are not a consequence of chronic inflammation, but are already present at the time of diagnosis.

Indexed as

Arthritis, RheumatoidSynovial MembraneAutoantibodiesCell DifferentiationHumansTranscriptomeAutoantibodies

Identifiers

PMID35831338
PMCPMC9279471
OpenAlexW4285086205

What OpenQuestion holds

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Registered trials

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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.