PMID- 32422945
OWN - NLM
STAT- MEDLINE
DCOM- 20210211
LR  - 20240328
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 10
DP  - 2020 May 14
TI  - Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients 
      with Systemic Lupus Erythematosus.
LID - 10.3390/ijms21103463 [doi]
LID - 3463
AB  - 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)-alpha2 
      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-alpha2, 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.
FAU - Parodis, Ioannis
AU  - Parodis I
AD  - Division of Rheumatology, Department of Medicine, Karolinska Institutet, SE-171 
      76 Stockholm, Sweden.
AD  - Rheumatology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
FAU - Akerstrom, Emil
AU  - Akerstrom E
AD  - Division of Rheumatology, Department of Medicine, Karolinska Institutet, SE-171 
      76 Stockholm, Sweden.
AD  - Rheumatology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
FAU - Sjowall, Christopher
AU  - Sjowall C
AD  - Rheumatology/Division of Inflammation and Infection, Department of Biomedical and 
      Clinical Sciences, Linkoping University, SE-581 85 Linkoping, Sweden.
FAU - Sohrabian, Azita
AU  - Sohrabian A
AD  - Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 
      Uppsala, Sweden.
FAU - Jonsen, Andreas
AU  - Jonsen A
AD  - Rheumatology, Department of Clinical Sciences Lund, Lund University, Skane 
      University Hospital, SE-222 42 Lund, Sweden.
FAU - Gomez, Alvaro
AU  - Gomez A
AD  - Division of Rheumatology, Department of Medicine, Karolinska Institutet, SE-171 
      76 Stockholm, Sweden.
AD  - Rheumatology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
FAU - Frodlund, Martina
AU  - Frodlund M
AD  - Rheumatology/Division of Inflammation and Infection, Department of Biomedical and 
      Clinical Sciences, Linkoping University, SE-581 85 Linkoping, Sweden.
FAU - Zickert, Agneta
AU  - Zickert A
AD  - Division of Rheumatology, Department of Medicine, Karolinska Institutet, SE-171 
      76 Stockholm, Sweden.
AD  - Rheumatology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
FAU - Bengtsson, Anders A
AU  - Bengtsson AA
AD  - Rheumatology, Department of Clinical Sciences Lund, Lund University, Skane 
      University Hospital, SE-222 42 Lund, Sweden.
FAU - Ronnelid, Johan
AU  - Ronnelid J
AD  - Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 
      Uppsala, Sweden.
FAU - Gunnarsson, Iva
AU  - Gunnarsson I
AD  - Division of Rheumatology, Department of Medicine, Karolinska Institutet, SE-171 
      76 Stockholm, Sweden.
AD  - Rheumatology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
LA  - eng
GR  - -/Vetenskapsradet/
GR  - R-859621; R-862161; R-844801/Reumatikerforbundet/
GR  - 2018-00250/Stiftelsen Professor Nanna Svartz Fond/
GR  - 2019-12/Ulla and Roland Gustafsson Foundation/
GR  - -/Stiftelsen Konung Gustaf V:s 80-arsfond/
GR  - -/Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse/
GR  - -/Region Ostergotland/
GR  - -/Stockholms Lans Landsting/
GR  - -/Landstinget i Uppsala lan/
GR  - -/Region Skane/
GR  - -/Alfred Osterlund's Foundation/
GR  - -/Medicinska Fakulteten, Lunds Universitet/
GR  - -/Greta och Johan Kocks stiftelser/
GR  - -/Skane University Hospital/
GR  - -/Karolinska Institutet/
GR  - -/Karolinska University Hospital/
GR  - -/Swedish Society of Medicine/
GR  - -/Ingegerd Johansson Donation/
PT  - Journal Article
DEP - 20200514
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Autoantibodies)
RN  - 0 (Cytokines)
RN  - 0 (IL10 protein, human)
RN  - 0 (Interferon alpha-2)
RN  - 0 (Interleukin-6)
RN  - 130068-27-8 (Interleukin-10)
RN  - 73B0K5S26A (belimumab)
SB  - IM
MH  - Adult
MH  - Antibodies, Antinuclear/blood
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage
MH  - Autoantibodies/*blood
MH  - Cytokines/blood
MH  - Female
MH  - Humans
MH  - Interferon alpha-2/blood
MH  - Interleukin-10/blood
MH  - Interleukin-6/blood
MH  - Lupus Erythematosus, Systemic/*blood/*drug therapy/immunology/pathology
MH  - Male
MH  - Middle Aged
MH  - Severity of Illness Index
MH  - Treatment Outcome
PMC - PMC7278961
OTO - NOTNLM
OT  - B cells
OT  - autoantibodies
OT  - autoimmunity
OT  - biologic therapies
OT  - cytokines
OT  - immune complexes
OT  - systemic lupus erythematosus
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript; or in the decision to publish the results.
EDAT- 2020/05/20 06:00
MHDA- 2021/02/12 06:00
PMCR- 2020/05/01
CRDT- 2020/05/20 06:00
PHST- 2020/03/28 00:00 [received]
PHST- 2020/05/02 00:00 [revised]
PHST- 2020/05/11 00:00 [accepted]
PHST- 2020/05/20 06:00 [entrez]
PHST- 2020/05/20 06:00 [pubmed]
PHST- 2021/02/12 06:00 [medline]
PHST- 2020/05/01 00:00 [pmc-release]
AID - ijms21103463 [pii]
AID - ijms-21-03463 [pii]
AID - 10.3390/ijms21103463 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 May 14;21(10):3463. doi: 10.3390/ijms21103463.