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Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus
- Source :
- International Journal of Molecular Sciences, Vol 21, Iss 3463, p 3463 (2020), International Journal of Molecular Sciences
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- We investigated whether belimumab treatment impacts on levels of autoantibodies and cytokines of interest in systemic lupus erythematosus (SLE). Longitudinally collected serum samples from 78 belimumab-treated Swedish SLE patients were analysed. Serum cytokine levels were determined using Luminex xMAP technology, and nuclear antigen autoantibody specificities using addressable laser bead immunoassay. In patients with detectable levels at baseline, interferon (IFN)-a2 levels were lower at month 6 (median; interquartile range (IQR): 8.9; 1.5-54.9 pg/mL) versus baseline (28.4; 20.9-100.3 pg/mL; p = 0.043). Interleukin (IL)-6 (baseline: 7.1; 2.9-16.1 pg/mL) decreased from month 6 (0.5; 0.5-6.3 pg/mL; p = 0.018) and throughout a 24 month follow-up. IL-10 (baseline: 12.6; 2.8-29.7 pg/mL) showed more rapid decreases from month 3 (1.8; 0.6-9.1 pg/mL; p = 0.003). Levels of anti-dsDNA (p < 0.001), anti-Smith antigen (Sm) (p = 0.002), anti-U1 small nuclear ribonucleoprotein (U1RNP) (p < 0.001), anti-Sm-U1RNP complex (p = 0.028), and anti-ribosomal P (p = 0.012) antibodies decreased from month 3 and remained decreased. Anti-Sm positivity at baseline was associated with higher probability and/or shorter time to achieve sustained SLE responder index-4 response (hazard ratio (HR): 2.52; 95% CI: 1.20-5.29; p = 0.015), independently of other factors. Decline of IL-6 levels through month 3 was greater in responders. In summary, belimumab treatment lowered IFN-a2, IL-6, and IL-10 levels, as well as levels of multiple autoantibodies, however after different time spans. Notably, anti-Sm positivity and early decline in IL-6 levels were associated with favorable treatment outcome. Funding agencies: The Swedish Research Council; Swedish RheumatismAssociation (R-859621; R-862161; R-844801); Professor Nanna Svartz Foundation (2018-00250); Ulla and Roland Gustafsson Foundation (2019-12); King Gustaf V’s 80-year Foundation; Swedish Society of Medicine; Ingegerd Johansson Donation; King Gustaf V and Queen Victoria’s Foundation of Freemasons; Region Östergötland (ALF grants); Region Stockholm; Region Uppsala; Region Skåne; Faculty of Medicine, Lund University; AlfredÖsterlund’s Foundation; Anna-Greta Crafoord Foundation; Greta and Johan Kock’s Foundation; Skåne UniversityHospital; and the Karolinska Institutet Foundations.
- Subjects :
- Adult
Male
autoantibodies
B cells
autoimmunity
biologic therapies
cytokines
immune complexes
systemic lupus erythematosus
Interferon alpha-2
Antibodies, Monoclonal, Humanized
Severity of Illness Index
Article
lcsh:Chemistry
Humans
Lupus Erythematosus, Systemic
lcsh:QH301-705.5
Rheumatology and Autoimmunity
Reumatologi och inflammation
Interleukin-6
Middle Aged
Interleukin-10
Treatment Outcome
lcsh:Biology (General)
lcsh:QD1-999
Antibodies, Antinuclear
Female
Subjects
Details
- Language :
- English
- ISSN :
- 16616596 and 14220067
- Volume :
- 21
- Issue :
- 3463
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.pmid.dedup....afc9dfb9b5d7ea0420b744e41167f191