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Article

Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus

1
Division of Rheumatology, Department of Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden
2
Rheumatology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
3
Rheumatology/Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, SE-581 85 Linköping, Sweden
4
Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden
5
Rheumatology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, SE-222 42 Lund, Sweden
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Int. J. Mol. Sci. 2020, 21(10), 3463; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103463
Received: 28 March 2020 / Revised: 2 May 2020 / Accepted: 11 May 2020 / Published: 14 May 2020
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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)-α2 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-α2, 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. View Full-Text
Keywords: systemic lupus erythematosus; cytokines; autoantibodies; immune complexes; autoimmunity; biologic therapies; B cells systemic lupus erythematosus; cytokines; autoantibodies; immune complexes; autoimmunity; biologic therapies; B cells
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MDPI and ACS Style

Parodis, I.; Åkerström, E.; Sjöwall, C.; Sohrabian, A.; Jönsen, A.; Gomez, A.; Frodlund, M.; Zickert, A.; Bengtsson, A.A.; Rönnelid, J.; Gunnarsson, I. Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus. Int. J. Mol. Sci. 2020, 21, 3463. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103463

AMA Style

Parodis I, Åkerström E, Sjöwall C, Sohrabian A, Jönsen A, Gomez A, Frodlund M, Zickert A, Bengtsson AA, Rönnelid J, Gunnarsson I. Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus. International Journal of Molecular Sciences. 2020; 21(10):3463. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103463

Chicago/Turabian Style

Parodis, Ioannis, Emil Åkerström, Christopher Sjöwall, Azita Sohrabian, Andreas Jönsen, Alvaro Gomez, Martina Frodlund, Agneta Zickert, Anders A. Bengtsson, Johan Rönnelid, and Iva Gunnarsson. 2020. "Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus" International Journal of Molecular Sciences 21, no. 10: 3463. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103463

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