Autoantibody and cytokine profiles during treatment with belimumab in patients with systemic lupus erythematosus
(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.
(Less)
- author
- organization
- publishing date
- 2020-05-14
- 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
- 2024-09-19 00:42:01
@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 < 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.</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}}, }