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Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus

BACKGROUND: An increased risk of pregnancy complications is seen in women with systemic lupus erythematosus (SLE), but the specific immunopathological drivers are still unclear. Hallmarks of SLE are granulocyte activation, type I interferon (IFN) overproduction, and autoantibodies. Here we examined...

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Autores principales: Torell, Agnes, Stockfelt, Marit, Larsson, Gunilla, Blennow, Kaj, Zetterberg, Henrik, Leonard, Dag, Rönnblom, Lars, Saleh, Muna, Sjöwall, Christopher, Strevens, Helena, Jönsen, Andreas, Bengtsson, Anders A., Trysberg, Estelle, Sennström, Maria Majcuk, Zickert, Agneta, Svenungsson, Elisabet, Gunnarsson, Iva, Christenson, Karin, Bylund, Johan, Jacobsson, Bo, Rudin, Anna, Lundell, Anna-Carin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10286457/
https://www.ncbi.nlm.nih.gov/pubmed/37349744
http://dx.doi.org/10.1186/s13075-023-03092-w
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author Torell, Agnes
Stockfelt, Marit
Larsson, Gunilla
Blennow, Kaj
Zetterberg, Henrik
Leonard, Dag
Rönnblom, Lars
Saleh, Muna
Sjöwall, Christopher
Strevens, Helena
Jönsen, Andreas
Bengtsson, Anders A.
Trysberg, Estelle
Sennström, Maria Majcuk
Zickert, Agneta
Svenungsson, Elisabet
Gunnarsson, Iva
Christenson, Karin
Bylund, Johan
Jacobsson, Bo
Rudin, Anna
Lundell, Anna-Carin
author_facet Torell, Agnes
Stockfelt, Marit
Larsson, Gunilla
Blennow, Kaj
Zetterberg, Henrik
Leonard, Dag
Rönnblom, Lars
Saleh, Muna
Sjöwall, Christopher
Strevens, Helena
Jönsen, Andreas
Bengtsson, Anders A.
Trysberg, Estelle
Sennström, Maria Majcuk
Zickert, Agneta
Svenungsson, Elisabet
Gunnarsson, Iva
Christenson, Karin
Bylund, Johan
Jacobsson, Bo
Rudin, Anna
Lundell, Anna-Carin
author_sort Torell, Agnes
collection PubMed
description BACKGROUND: An increased risk of pregnancy complications is seen in women with systemic lupus erythematosus (SLE), but the specific immunopathological drivers are still unclear. Hallmarks of SLE are granulocyte activation, type I interferon (IFN) overproduction, and autoantibodies. Here we examined whether low-density granulocytes (LDG) and granulocyte activation increase during pregnancy, and related the results to IFNα protein levels, autoantibody profile, and gestational age at birth. METHODS: Repeated blood samples were collected during pregnancy in trimesters one, two, and three from 69 women with SLE and 27 healthy pregnant women (HC). Nineteen of the SLE women were also sampled late postpartum. LDG proportions and granulocyte activation (CD62L shedding) were measured by flow cytometry. Plasma IFNα protein concentrations were quantified by single molecule array (Simoa) immune assay. Clinical data were obtained from medical records. RESULTS: Women with SLE had higher LDG proportions and increased IFNα protein levels compared to HC throughout pregnancy, but neither LDG fractions nor IFNα levels differed during pregnancy compared to postpartum in SLE. Granulocyte activation status was higher in SLE relative to HC pregnancies, and it was increased during pregnancy compared to after pregnancy in SLE. Higher LDG proportions in SLE were associated with antiphospholipid positivity but not to IFNα protein levels. Finally, higher LDG proportions in trimester three correlated independently with lower gestational age at birth in SLE. CONCLUSION: Our results suggest that SLE pregnancy results in increased peripheral granulocyte priming, and that higher LDG proportions late in pregnancy are related to shorter pregnancy duration but not to IFNα blood levels in SLE. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-023-03092-w.
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spelling pubmed-102864572023-06-23 Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus Torell, Agnes Stockfelt, Marit Larsson, Gunilla Blennow, Kaj Zetterberg, Henrik Leonard, Dag Rönnblom, Lars Saleh, Muna Sjöwall, Christopher Strevens, Helena Jönsen, Andreas Bengtsson, Anders A. Trysberg, Estelle Sennström, Maria Majcuk Zickert, Agneta Svenungsson, Elisabet Gunnarsson, Iva Christenson, Karin Bylund, Johan Jacobsson, Bo Rudin, Anna Lundell, Anna-Carin Arthritis Res Ther Research BACKGROUND: An increased risk of pregnancy complications is seen in women with systemic lupus erythematosus (SLE), but the specific immunopathological drivers are still unclear. Hallmarks of SLE are granulocyte activation, type I interferon (IFN) overproduction, and autoantibodies. Here we examined whether low-density granulocytes (LDG) and granulocyte activation increase during pregnancy, and related the results to IFNα protein levels, autoantibody profile, and gestational age at birth. METHODS: Repeated blood samples were collected during pregnancy in trimesters one, two, and three from 69 women with SLE and 27 healthy pregnant women (HC). Nineteen of the SLE women were also sampled late postpartum. LDG proportions and granulocyte activation (CD62L shedding) were measured by flow cytometry. Plasma IFNα protein concentrations were quantified by single molecule array (Simoa) immune assay. Clinical data were obtained from medical records. RESULTS: Women with SLE had higher LDG proportions and increased IFNα protein levels compared to HC throughout pregnancy, but neither LDG fractions nor IFNα levels differed during pregnancy compared to postpartum in SLE. Granulocyte activation status was higher in SLE relative to HC pregnancies, and it was increased during pregnancy compared to after pregnancy in SLE. Higher LDG proportions in SLE were associated with antiphospholipid positivity but not to IFNα protein levels. Finally, higher LDG proportions in trimester three correlated independently with lower gestational age at birth in SLE. CONCLUSION: Our results suggest that SLE pregnancy results in increased peripheral granulocyte priming, and that higher LDG proportions late in pregnancy are related to shorter pregnancy duration but not to IFNα blood levels in SLE. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-023-03092-w. BioMed Central 2023-06-22 2023 /pmc/articles/PMC10286457/ /pubmed/37349744 http://dx.doi.org/10.1186/s13075-023-03092-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Torell, Agnes
Stockfelt, Marit
Larsson, Gunilla
Blennow, Kaj
Zetterberg, Henrik
Leonard, Dag
Rönnblom, Lars
Saleh, Muna
Sjöwall, Christopher
Strevens, Helena
Jönsen, Andreas
Bengtsson, Anders A.
Trysberg, Estelle
Sennström, Maria Majcuk
Zickert, Agneta
Svenungsson, Elisabet
Gunnarsson, Iva
Christenson, Karin
Bylund, Johan
Jacobsson, Bo
Rudin, Anna
Lundell, Anna-Carin
Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus
title Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus
title_full Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus
title_fullStr Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus
title_full_unstemmed Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus
title_short Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus
title_sort low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10286457/
https://www.ncbi.nlm.nih.gov/pubmed/37349744
http://dx.doi.org/10.1186/s13075-023-03092-w
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