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Integrated single c...
Integrated single cell and spatial transcriptomics reveal autoreactive differentiated B cells in joints of early rheumatoid arthritis
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- Hardt, Uta (author)
- Karolinska Inst, Ctr Mol Med, Dept Med Solna, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
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- Carlberg, Konstantin (author)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab
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- af Klint, Erik (author)
- Karolinska Inst, Ctr Mol Med, Dept Med Solna, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.
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- Sahlstrom, Peter (author)
- Karolinska Institutet
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- Larsson, Ludvig (author)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab
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- van Vollenhoven, Annika (author)
- Karolinska Inst, Ctr Mol Med, Dept Med Solna, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.
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- Machado, Susana Hernandez (author)
- Karolinska Inst, Ctr Mol Med, Dept Med Solna, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.
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- Israelsson, Lena (author)
- Karolinska Inst, Ctr Mol Med, Dept Med Solna, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.
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- Amara, Khaled (author)
- Karolinska Inst, Ctr Mol Med, Dept Med Solna, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.
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- Chemin, Karine (author)
- Karolinska Institutet
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- Korotkova, Marina (author)
- Karolinska Institutet
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- Hedestam, Gunilla B. Karlsson (author)
- Karolinska Institutet
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- Catrina, Anca, I (author)
- Karolinska Inst, Ctr Mol Med, Dept Med Solna, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.
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- Teichmann, Sarah A. (author)
- Wellcome Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England.
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- Ståhl, Patrik, Dr. (author)
- KTH,Science for Life Laboratory, SciLifeLab,Genteknologi
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- Malmstrom, Vivianne (author)
- Karolinska Institutet
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Karolinska Inst, Ctr Mol Med, Dept Med Solna, Div Rheumatol, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. Genteknologi (creator_code:org_t)
- 2022-07-13
- 2022
- English.
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
- Related links:
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- TEKNIK OCH TEKNOLOGIER -- Annan teknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Other Engineering and Technologies (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Hardt, Uta
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Carlberg, Konsta ...
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af Klint, Erik
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Sahlstrom, Peter
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Larsson, Ludvig
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van Vollenhoven, ...
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Machado, Susana ...
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Israelsson, Lena
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Amara, Khaled
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Chemin, Karine
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Korotkova, Marin ...
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Hedestam, Gunill ...
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Catrina, Anca, I
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Teichmann, Sarah ...
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Ståhl, Patrik, D ...
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Malmstrom, Vivia ...
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- About the subject
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- ENGINEERING AND TECHNOLOGY
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ENGINEERING AND ...
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and Other Engineerin ...
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Scientific Repor ...
- By the university
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Royal Institute of Technology
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Karolinska Institutet