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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

Torell, Agnes ; Stockfelt, Marit ; Larsson, Gunilla ; Blennow, Kaj LU ; Zetterberg, Henrik LU ; Leonard, Dag ; Rönnblom, Lars ; Saleh, Muna LU ; Sjöwall, Christopher and Strevens, Helena LU , et al. (2023) In Arthritis Research and Therapy 25(1).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Autoantibody(ies), Interferon alpha, Neutrophils, Pregnancy, Systemic lupus erythematosus (SLE)
in
Arthritis Research and Therapy
volume
25
issue
1
article number
107
publisher
BioMed Central (BMC)
external identifiers
  • pmid:37349744
  • scopus:85162752452
ISSN
1478-6354
DOI
10.1186/s13075-023-03092-w
language
English
LU publication?
yes
id
546b3093-87a8-4433-8187-45a8e5a55280
date added to LUP
2023-08-25 14:06:51
date last changed
2024-04-20 01:50:58
@article{546b3093-87a8-4433-8187-45a8e5a55280,
  abstract     = {{<p>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.</p>}},
  author       = {{Torell, Agnes and Stockfelt, Marit and Larsson, Gunilla and Blennow, Kaj and Zetterberg, Henrik and Leonard, Dag and Rönnblom, Lars and Saleh, Muna and Sjöwall, Christopher and Strevens, Helena and Jönsen, Andreas and Bengtsson, Anders A. and Trysberg, Estelle and Sennström, Maria Majcuk and Zickert, Agneta and Svenungsson, Elisabet and Gunnarsson, Iva and Christenson, Karin and Bylund, Johan and Jacobsson, Bo and Rudin, Anna and Lundell, Anna Carin}},
  issn         = {{1478-6354}},
  keywords     = {{Autoantibody(ies); Interferon alpha; Neutrophils; Pregnancy; Systemic lupus erythematosus (SLE)}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Arthritis Research and Therapy}},
  title        = {{Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus}},
  url          = {{http://dx.doi.org/10.1186/s13075-023-03092-w}},
  doi          = {{10.1186/s13075-023-03092-w}},
  volume       = {{25}},
  year         = {{2023}},
}