Author:
Torell Agnes,Stockfelt Marit,Blennow Kaj,Zetterberg Henrik,Akhter Tansim,Leonard Dag,Rönnblom Lars,Pihl Sofia,Saleh Muna,Sjöwall Christopher,Strevens Helena,Jönsen Andreas,Bengtsson Anders A.,Trysberg Estelle,Majczuk Sennström Maria,Zickert Agneta,Svenungsson Elisabet,Gunnarsson Iva,Bylund Johan,Jacobsson Bo,Rudin Anna,Lundell Anna-Carin
Abstract
Abstract
Background
Lymphopenia, autoantibodies and activation of the type I interferon (IFN) system are common features in systemic lupus erythematosus (SLE). We speculate whether lymphocyte subset counts are affected by pregnancy and if they relate to autoantibody profiles and/or IFNα protein in SLE pregnancy.
Methods
Repeated blood samples were collected during pregnancy from 80 women with SLE and 51 healthy controls (HC). Late postpartum samples were obtained from 19 of the women with SLE. Counts of CD4 + and CD8 + T cells, B cells and NK cells were measured by flow cytometry. Positivity for anti-nuclear antibodies (ANA) fine specificities (double-stranded DNA [dsDNA], Smith [Sm], ribonucleoprotein [RNP], chromatin, Sjögren’s syndrome antigen A [SSA] and B [SSB]) and anti-phospholipid antibodies (cardiolipin [CL] and β2 glycoprotein I [β2GPI]) was assessed with multiplexed bead assay. IFNα protein 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. Principal 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-chromatin), 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.
Funder
The Swedish Rheumatism Association
The Gothenburg Society of Medicine
The Swedish Society of Medicine
The Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement
Foundation of Ingegerd Johansson
The Swedish Research Council
Foundation of IngaBritt and Arne Lundberg
Foundations of The King Gustaf V’s 80th Birthday found
Foundation of Ulla and Roland Gustafsson
Foundation of Nanna Svartz
Foundation of Rune and Ulla Amlöv
Foundation of Hjalmar Svensson
Foundation of Emil and Wera Cornell
University of Gothenburg
Publisher
Springer Science and Business Media LLC
Cited by
1 articles.
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