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Autoantibody and cytokine profiles during treatment with belimumab in patients with systemic lupus erythematosus

Parodis, Ioannis ; Åkerström, Emil ; Sjöwall, Christopher ; Sohrabian, Azita ; Jönsen, Andreas LU ; Gomez, Alvaro ; Frodlund, Martina ; Zickert, Agneta ; Bengtsson, Anders A. LU and Rönnelid, Johan , et al. (2020) In International Journal of Molecular Sciences 21(10).
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)-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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Autoantibodies, Autoimmunity, B cells, Biologic therapies, Cytokines, Immune complexes, Systemic lupus erythematosus
in
International Journal of Molecular Sciences
volume
21
issue
10
article number
3463
publisher
MDPI AG
external identifiers
  • scopus:85085133881
  • pmid:32422945
ISSN
1661-6596
DOI
10.3390/ijms21103463
language
English
LU publication?
yes
id
e285d899-fbad-4146-b955-c94a80f7cd6d
date added to LUP
2020-06-16 17:16:35
date last changed
2024-04-17 10:20:27
@article{e285d899-fbad-4146-b955-c94a80f7cd6d,
  abstract     = {{<p>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 &lt; 0.001), anti-Smith antigen (Sm) (p = 0.002), anti-U1 small nuclear ribonucleoprotein (U1RNP) (p &lt; 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.</p>}},
  author       = {{Parodis, Ioannis and Åkerström, Emil and Sjöwall, Christopher and Sohrabian, Azita and Jönsen, Andreas and Gomez, Alvaro and Frodlund, Martina and Zickert, Agneta and Bengtsson, Anders A. and Rönnelid, Johan and Gunnarsson, Iva}},
  issn         = {{1661-6596}},
  keywords     = {{Autoantibodies; Autoimmunity; B cells; Biologic therapies; Cytokines; Immune complexes; Systemic lupus erythematosus}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{10}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Autoantibody and cytokine profiles during treatment with belimumab in patients with systemic lupus erythematosus}},
  url          = {{http://dx.doi.org/10.3390/ijms21103463}},
  doi          = {{10.3390/ijms21103463}},
  volume       = {{21}},
  year         = {{2020}},
}