Plasma Interferon-alpha Protein Levels During Pregnancy Are Associated with Lower Birth Weight in Systemic Lupus Erythematosus

Overview

Journal Rheumatology (Oxford)

Publisher Oxford University Press

Specialty Rheumatology

Date 2024 Jun 14

PMID 38876981

Authors

Marit Stockfelt

Agnes Torell

Iva Gunnarsson

Elisabet Svenungsson

Agneta Zickert

Maria Majcuk Sennstrom

Estelle Trysberg

Anders A Bengtsson

Andreas Jonsen

Helena Strevens

Christopher Sjowall

Muna Saleh

Sofia Pihl

Dag Leonard

Lars Ronnblom

Tansim Akhter

Kaj Blennow

Henrik Zetterberg

Bo Jacobsson

Anna-Carin Lundell

Anna Rudin

Affiliations

Soon will be listed here.

Abstract

Objectives: Adverse pregnancy outcomes are more common in women with SLE compared with healthy women, but we lack prognostic biomarkers. Plasma IFN-α protein levels are elevated in a subgroup of pregnant women with SLE, but whether this is associated with pregnancy outcomes is unknown. We investigated the relationship between IFN-α, adverse pregnancy outcomes and the presence of autoantibodies in SLE pregnancy.

Methods: We followed 76 women with SLE prospectively. Protein levels of IFN-α were quantified in plasma collected in the second and third trimester with single-molecule array. Positivity for ANA and aPL antibodies was assessed during late pregnancy with multiplexed bead assay. Clinical outcomes included the adverse pregnancy outcomes small for gestational age (SGA), preterm birth and preeclampsia.

Results: During SLE pregnancy, women with SGA infants compared with those without had higher levels of plasma IFN-α protein, and IFN-α positivity was associated with lower birth weight of the infant. Preterm birth was associated with autoantibodies against chromatin. IFN-α protein levels associated positively with autoantibodies against chromatin, Smith/RNP (SmRNP) and RNP, but negatively with aPL antibodies.

Conclusion: Elevated IFN-α protein in plasma of women with SLE is a potential risk factor for lower birth weight of their infants. The association between IFN-α and lower birth weight warrants further investigation regarding the pathophysiological role of IFN-α during SLE pregnancy.

Citing Articles

Antiphospholipid Antibodies as Key Players in Systemic Lupus Erythematosus: The Relationship with Cytokines and Immune Dysregulation.

Richter P, Badescu M, Rezus C, Ouatu A, Dima N, Popescu D Int J Mol Sci. 2024; 25(20).

PMID: 39457063 PMC: 11509045. DOI: 10.3390/ijms252011281.

References

Lien H, Pedersen T, Jakobsen B, Flatberg A, Chawla K, Saetrom P . Single-cell resolution of longitudinal blood transcriptome profiles in rheumatoid arthritis, systemic lupus erythematosus and healthy control pregnancies. Ann Rheum Dis. 2023; 83(3):300-311. PMC: 10894842. DOI: 10.1136/ard-2023-224644. View

Hong S, Banchereau R, Maslow B, Guerra M, Cardenas J, Baisch J . Longitudinal profiling of human blood transcriptome in healthy and lupus pregnancy. J Exp Med. 2019; 216(5):1154-1169. PMC: 6504211. DOI: 10.1084/jem.20190185. View

He W, Wei H . Maternal and fetal complications associated with systemic lupus erythematosus: An updated meta-analysis of the most recent studies (2017-2019). Medicine (Baltimore). 2020; 99(16):e19797. PMC: 7440247. DOI: 10.1097/MD.0000000000019797. View

Torell A, Stockfelt M, Blennow K, Zetterberg H, Akhter T, Leonard D . Low CD4 + T cell count is related to specific anti-nuclear antibodies, IFNα protein positivity and disease activity in systemic lupus erythematosus pregnancy. Arthritis Res Ther. 2024; 26(1):65. PMC: 10924387. DOI: 10.1186/s13075-024-03301-0. View

Mathian A, Mouries-Martin S, Dorgham K, Devilliers H, Barnabei L, Ben Salah E . Monitoring Disease Activity in Systemic Lupus Erythematosus With Single-Molecule Array Digital Enzyme-Linked Immunosorbent Assay Quantification of Serum Interferon-α. Arthritis Rheumatol. 2018; 71(5):756-765. DOI: 10.1002/art.40792. View

Torell A, Stockfelt M, Larsson G, Blennow K, Zetterberg H, Leonard D . Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus. Arthritis Res Ther. 2023; 25(1):107. PMC: 10286457. DOI: 10.1186/s13075-023-03092-w. View

Chasset F, Mathian A, Dorgham K, Ribi C, Trendelenburg M, Huynh-Do U . Serum interferon-α levels and IFN type I-stimulated genes score perform equally to assess systemic lupus erythematosus disease activity. Ann Rheum Dis. 2022; 81(6):901-903. DOI: 10.1136/annrheumdis-2021-221835. View

Kirou K, Lee C, George S, Louca K, Peterson M, Crow M . Activation of the interferon-alpha pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. Arthritis Rheum. 2005; 52(5):1491-503. DOI: 10.1002/art.21031. View

Stockfelt M, Larsson G, Engstrom H, Puttonen H, Zetterberg H, Blennow K . Activated low-density granulocytes in peripheral and intervillous blood and neutrophil inflammation in placentas from SLE pregnancies. Lupus Sci Med. 2021; 8(1). PMC: 7942245. DOI: 10.1136/lupus-2020-000463. View

10.

Cervera R, Vinas O, Ramos-Casals M, Font J, Garcia-Carrasco M, Siso A . Anti-chromatin antibodies in systemic lupus erythematosus: a useful marker for lupus nephropathy. Ann Rheum Dis. 2003; 62(5):431-4. PMC: 1754546. DOI: 10.1136/ard.62.5.431. View

11.

Clowse M, Magder L, Petri M . The clinical utility of measuring complement and anti-dsDNA antibodies during pregnancy in patients with systemic lupus erythematosus. J Rheumatol. 2011; 38(6):1012-6. DOI: 10.3899/jrheum.100746. View

12.

Arnaud L, Furie R, Morand E, Aringer M, Peschken C, Desta B . Burden of systemic lupus erythematosus in clinical practice: baseline data from the SLE Prospective Observational Cohort Study (SPOCS) by interferon gene signature. Lupus Sci Med. 2023; 10(2). DOI: 10.1136/lupus-2023-001032. View

13.

Marsal K, Persson P, Larsen T, Lilja H, Selbing A, Sultan B . Intrauterine growth curves based on ultrasonically estimated foetal weights. Acta Paediatr. 1996; 85(7):843-8. DOI: 10.1111/j.1651-2227.1996.tb14164.x. View

14.

Eloranta M, Lovgren T, Finke D, Mathsson L, Ronnelid J, Kastner B . Regulation of the interferon-alpha production induced by RNA-containing immune complexes in plasmacytoid dendritic cells. Arthritis Rheum. 2009; 60(8):2418-27. DOI: 10.1002/art.24686. View

15.

Reynolds J, Briggs T, Rice G, Darmalinggam S, Bondet V, Bruce E . Type I interferon in patients with systemic autoimmune rheumatic disease is associated with haematological abnormalities and specific autoantibody profiles. Arthritis Res Ther. 2019; 21(1):147. PMC: 6567906. DOI: 10.1186/s13075-019-1929-4. View

16.

Hubbard E, Pisetsky D, Lipsky P . Anti-RNP antibodies are associated with the interferon gene signature but not decreased complement levels in SLE. Ann Rheum Dis. 2022; 81(5):632-643. DOI: 10.1136/annrheumdis-2021-221662. View

17.

Mathian A, Mouries-Martin S, Dorgham K, Devilliers H, Yssel H, Garrido Castillo L . Ultrasensitive serum interferon-α quantification during SLE remission identifies patients at risk for relapse. Ann Rheum Dis. 2019; 78(12):1669-1676. DOI: 10.1136/annrheumdis-2019-215571. View

18.

Wada H, Nagano H, Yamamoto H, Noda T, Murakami M, Kobayashi S . Combination of interferon-alpha and 5-fluorouracil inhibits endothelial cell growth directly and by regulation of angiogenic factors released by tumor cells. BMC Cancer. 2009; 9:361. PMC: 2767355. DOI: 10.1186/1471-2407-9-361. View

19.

Morand E, Furie R, Tanaka Y, Bruce I, Askanase A, Richez C . Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2019; 382(3):211-221. DOI: 10.1056/NEJMoa1912196. View

20.

Cortes-Hernandez J, Ordi-Ros J, Paredes F, Casellas M, Castillo F, Vilardell-Tarres M . Clinical predictors of fetal and maternal outcome in systemic lupus erythematosus: a prospective study of 103 pregnancies. Rheumatology (Oxford). 2002; 41(6):643-50. DOI: 10.1093/rheumatology/41.6.643. View