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  • P146 Low CD4+ T cell count is related to specific anti-nuclear antibodies, IFNα protein positivity and disease activity in systemic lupus erythematosus pregnancy

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P146 Low CD4+ T cell count is related to specific anti-nuclear antibodies, IFNα protein positivity and disease activity in systemic lupus erythematosus pregnancy
  1. Agnes Torell1,
  2. Marit Stockfelt1,2,
  3. Kaj Blennow3,4,5,6,
  4. Henrik Zetterberg3,4,7,8,9,10,
  5. Tansim Akhter11,
  6. Dag Leonard12,
  7. Lars Rönnblom12,
  8. Sofia Pihl13,14,
  9. Muna Saleh15,
  10. Christopher Sjöwall15,
  11. Helena Strevens16,
  12. Andreas Jönsen17,
  13. Anders A Bengtsson17,
  14. Estelle Trysberg2,
  15. Maria Majcuk Sennström18,
  16. Agneta Zickert19,
  17. Elisabet Svenungsson19,
  18. Iva Gunnarsson19,
  19. Johan Bylund20,
  20. Bo Jacobsson21,22,23,
  21. Anna Rudin1 and
  22. Anna-Carin Lundell1
  1. 1Dept. of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Sweden
  2. 2Rheumatology, Sahlgrenska University Hospital, Gothenburg, Sweden
  3. 3Dept. of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
  4. 4Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
  5. 5Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
  6. 6Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine and Dept. of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, P.R. China
  7. 7Dept. of Neurodegenerative Disease, UCL Institute of Neurology, London, UK
  8. 8UK Dementia Research Institute at UCL, London, UK
  9. 9Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China
  10. 10Winsconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
  11. 11Dept. of Women’s and Children’s Health, Section of Obstetrics and Gynecology, Uppsala University, Uppsala, Sweden
  12. 12Dept. of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden
  13. 13Dept. of Obstetrics and Gynecology, Linköping University Hospital
  14. 14Dept. of Biomedical and Clinical Sciences, Division of Children’s and Women’s Health, Linköping University, Linköping, Sweden
  15. 15Division of Inflammation and Infection, Dept. of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
  16. 16Dept. of Obstetrics and Gynecology, Institute of Clinical Sciences, Skåne University Hospital, Lund, Sweden
  17. 17Dept. of Clinical Sciences Lund, Rheumatology, Lund University, Skåne University Hospital, Lund, Sweden
  18. 18Dept. of Womens and Childrens Health, Division for Obstetrics and Gynecology, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden
  19. 19Division of Rheumatology, Dept. of Medicine Solna, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
  20. 20Dept. of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy at the University of Gothenburg, Sweden
  21. 21Dept. of Obstetrics and Gynecology, Sahlgrenska University Hospital, Gothenburg Sweden
  22. 22Dept. of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg Sweden
  23. 23Dept. of Genetics and Bioinformatics, Division of Health Data and Digitalisation, Institute of Public Health, Oslo, Norway

Abstract

Objective Adverse pregnancy outcomes are more common among women with systemic lupus erythematosus (SLE) compared to healthy women, but there is limited understanding on how pregnancy affects the immune system and what specific immunopathological processes that precede these complications. Lymphopenia, autoantibodies and activation of the type I interferon (IFN) system are common features SLE. We aimed to investigate the impact of pregnancy on lymphocyte subset counts in SLE and their associations with autoantibody profiles and IFNα concentrations.

Methods Repeated blood samples were collected from 80 pregnant women with SLE and 51 healthy controls (HC), with additional samples from 19 women with SLE postpartum. Flow cytometry was used to measure CD4+ and CD8+ T cells, B cells, and NK cells. Positivity for anti-nuclear antibodies (ANA) fine specificities and anti-phospholipid antibodies was assessed using multiplexed bead assay. IFNα concentration was quantified with Single molecule array (Simoa) immune assay. Clinical data were retrieved from medical records.

Results Women with SLE had lower counts of all lymphocyte subsets compared to HC throughout pregnancy, but counts did not differ during pregnancy compared to postpartum. Principle component analysis revealed that low lymphocyte subset counts differentially related to autoantibody profiles, cluster one (anti-dsDNA/anti-Sm/anti-RNP/anti-Sm/RNP/anti-chormatin), cluster two (anti-SSA/anti-SSB) and cluster three (anti-CL/anti-β2GPI), IFNα protein levels and disease activity. CD4+ T cell counts were lower in women positive to all ANA fine specificities in cluster one compared to those who were negative, and B cell numbers were lower in women positive for anti-dsDNA and anti-Sm compared to negative women. Moreover, CD4+ T cell and B cell counts were lower in women with moderate/high compared to no/low disease activity, and CD4+ T cell count was lower in IFNα protein positive relative to negative women. Finally, CD4+ T cell count was unrelated to treatment.

Conclusion Lymphocyte subset counts are lower in SLE compared to healthy pregnancies, which seems to be a feature of the disease per se and not affected by pregnancy. Our results also indicate that low lymphocyte subset counts relate differentially to autoantibody profiles, IFNα protein levels and disease activity, which could be due to divergent disease pathways.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ .

https://doi.org/10.1136/lupus-2024-el.200

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