Single-cell resolution of longitudinal blood transcriptome profiles in rheumatoid arthritis, systemic lupus erythematosus and healthy control pregnancies
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ..
OBJECTIVES: Comparative longitudinal analyses of cellular composition and peripheral blood gene expression in Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and healthy pregnancies.
METHODS: In total, 335 whole blood samples from 84 RA, SLE and healthy controls before pregnancy, at each trimester, 6 weeks, 6 months and 12 months post partum were analysed. We combined bulk and single cell RNA analyses for cell-type estimation, validated by flow cytometry, before combining this in a cell-type adjusted analysis for an improved resolution of unrecognised gene expression changes associated with RA and SLE pregnancies.
RESULTS: Patients were well regulated throughout pregnancy, and few had pregnancy complications. In SLE, the interferon signature was augmented during pregnancy, and the pregnancy signature was continued post partum. An altered cell type composition strongly influences the profile. In the pregnancy signature, transcripts involved in galactosylation potentially altering the effector functions of autoantibodies became more evident. Several genes in the adjusted RA signature are expressed in mucosal associated invariant T cells.
CONCLUSION: We found distinct RA, SLE and pregnancy signatures, and no expression patterns could be attributed to medication or disease activity. Our results support the need for close postpartum follow-up of patients with SLE. Gene expression patterns in RA were closer to healthy controls than to SLE, and primarily became evident after cell-type adjustment. Adjusting for cell abundance unravelled gene expression signatures less associated with variation in cell-composition and highlighted genes with expression profiles associated with changes in specialised cell populations.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:83 |
|---|---|
| Enthalten in: |
Annals of the rheumatic diseases - 83(2024), 3 vom: 15. Feb., Seite 300-311 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lien, Hilde Julie T [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
9008-11-1 |
|---|
| Anmerkungen: |
Date Completed 19.02.2024 Date Revised 28.02.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1136/ard-2023-224644 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM365409294 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM365409294 | ||
| 003 | DE-627 | ||
| 005 | 20240229170503.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1136/ard-2023-224644 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1310.xml |
| 035 | |a (DE-627)NLM365409294 | ||
| 035 | |a (NLM)38049980 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lien, Hilde Julie T |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Single-cell resolution of longitudinal blood transcriptome profiles in rheumatoid arthritis, systemic lupus erythematosus and healthy control pregnancies |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 19.02.2024 | ||
| 500 | |a Date Revised 28.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a OBJECTIVES: Comparative longitudinal analyses of cellular composition and peripheral blood gene expression in Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and healthy pregnancies | ||
| 520 | |a METHODS: In total, 335 whole blood samples from 84 RA, SLE and healthy controls before pregnancy, at each trimester, 6 weeks, 6 months and 12 months post partum were analysed. We combined bulk and single cell RNA analyses for cell-type estimation, validated by flow cytometry, before combining this in a cell-type adjusted analysis for an improved resolution of unrecognised gene expression changes associated with RA and SLE pregnancies | ||
| 520 | |a RESULTS: Patients were well regulated throughout pregnancy, and few had pregnancy complications. In SLE, the interferon signature was augmented during pregnancy, and the pregnancy signature was continued post partum. An altered cell type composition strongly influences the profile. In the pregnancy signature, transcripts involved in galactosylation potentially altering the effector functions of autoantibodies became more evident. Several genes in the adjusted RA signature are expressed in mucosal associated invariant T cells | ||
| 520 | |a CONCLUSION: We found distinct RA, SLE and pregnancy signatures, and no expression patterns could be attributed to medication or disease activity. Our results support the need for close postpartum follow-up of patients with SLE. Gene expression patterns in RA were closer to healthy controls than to SLE, and primarily became evident after cell-type adjustment. Adjusting for cell abundance unravelled gene expression signatures less associated with variation in cell-composition and highlighted genes with expression profiles associated with changes in specialised cell populations | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Arthritis, Rheumatoid | |
| 650 | 4 | |a Autoimmune Diseases | |
| 650 | 4 | |a Autoimmunity | |
| 650 | 4 | |a Lupus Erythematosus, Systemic | |
| 650 | 7 | |a Interferons |2 NLM | |
| 650 | 7 | |a 9008-11-1 |2 NLM | |
| 700 | 1 | |a Pedersen, Tina T |e verfasserin |4 aut | |
| 700 | 1 | |a Jakobsen, Bente |e verfasserin |4 aut | |
| 700 | 1 | |a Flatberg, Arnar |e verfasserin |4 aut | |
| 700 | 1 | |a Chawla, Konika |e verfasserin |4 aut | |
| 700 | 1 | |a Sætrom, Pål |e verfasserin |4 aut | |
| 700 | 1 | |a Fenstad, Mona H |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Annals of the rheumatic diseases |d 1939 |g 83(2024), 3 vom: 15. Feb., Seite 300-311 |w (DE-627)NLM000174114 |x 1468-2060 |7 nnns |
| 773 | 1 | 8 | |g volume:83 |g year:2024 |g number:3 |g day:15 |g month:02 |g pages:300-311 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1136/ard-2023-224644 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 83 |j 2024 |e 3 |b 15 |c 02 |h 300-311 | ||