Cargando…

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

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 xM...

Descripción completa

Detalles Bibliográficos
Autores principales: Parodis, Ioannis, Åkerström, Emil, Sjöwall, Christopher, Sohrabian, Azita, Jönsen, Andreas, Gomez, Alvaro, Frodlund, Martina, Zickert, Agneta, Bengtsson, Anders A, Rönnelid, Johan, Gunnarsson, Iva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278961/
https://www.ncbi.nlm.nih.gov/pubmed/32422945
http://dx.doi.org/10.3390/ijms21103463
_version_ 1783543452313583616
author Parodis, Ioannis
Åkerström, Emil
Sjöwall, Christopher
Sohrabian, Azita
Jönsen, Andreas
Gomez, Alvaro
Frodlund, Martina
Zickert, Agneta
Bengtsson, Anders A
Rönnelid, Johan
Gunnarsson, Iva
author_facet Parodis, Ioannis
Åkerström, Emil
Sjöwall, Christopher
Sohrabian, Azita
Jönsen, Andreas
Gomez, Alvaro
Frodlund, Martina
Zickert, Agneta
Bengtsson, Anders A
Rönnelid, Johan
Gunnarsson, Iva
author_sort Parodis, Ioannis
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7278961
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-72789612020-06-15 Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus Parodis, Ioannis Åkerström, Emil Sjöwall, Christopher Sohrabian, Azita Jönsen, Andreas Gomez, Alvaro Frodlund, Martina Zickert, Agneta Bengtsson, Anders A Rönnelid, Johan Gunnarsson, Iva Int J Mol Sci Article 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. MDPI 2020-05-14 /pmc/articles/PMC7278961/ /pubmed/32422945 http://dx.doi.org/10.3390/ijms21103463 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Parodis, Ioannis
Åkerström, Emil
Sjöwall, Christopher
Sohrabian, Azita
Jönsen, Andreas
Gomez, Alvaro
Frodlund, Martina
Zickert, Agneta
Bengtsson, Anders A
Rönnelid, Johan
Gunnarsson, Iva
Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus
title Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus
title_full Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus
title_fullStr Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus
title_full_unstemmed Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus
title_short Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus
title_sort autoantibody and cytokine profiles during treatment with belimumab in patients with systemic lupus erythematosus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278961/
https://www.ncbi.nlm.nih.gov/pubmed/32422945
http://dx.doi.org/10.3390/ijms21103463
work_keys_str_mv AT parodisioannis autoantibodyandcytokineprofilesduringtreatmentwithbelimumabinpatientswithsystemiclupuserythematosus
AT akerstromemil autoantibodyandcytokineprofilesduringtreatmentwithbelimumabinpatientswithsystemiclupuserythematosus
AT sjowallchristopher autoantibodyandcytokineprofilesduringtreatmentwithbelimumabinpatientswithsystemiclupuserythematosus
AT sohrabianazita autoantibodyandcytokineprofilesduringtreatmentwithbelimumabinpatientswithsystemiclupuserythematosus
AT jonsenandreas autoantibodyandcytokineprofilesduringtreatmentwithbelimumabinpatientswithsystemiclupuserythematosus
AT gomezalvaro autoantibodyandcytokineprofilesduringtreatmentwithbelimumabinpatientswithsystemiclupuserythematosus
AT frodlundmartina autoantibodyandcytokineprofilesduringtreatmentwithbelimumabinpatientswithsystemiclupuserythematosus
AT zickertagneta autoantibodyandcytokineprofilesduringtreatmentwithbelimumabinpatientswithsystemiclupuserythematosus
AT bengtssonandersa autoantibodyandcytokineprofilesduringtreatmentwithbelimumabinpatientswithsystemiclupuserythematosus
AT ronnelidjohan autoantibodyandcytokineprofilesduringtreatmentwithbelimumabinpatientswithsystemiclupuserythematosus
AT gunnarssoniva autoantibodyandcytokineprofilesduringtreatmentwithbelimumabinpatientswithsystemiclupuserythematosus