TY - JOUR
T1 - Angiogenic cytokines can reflect the synovitis severity and treatment response to biologics in rheumatoid arthritis
AU - Kim, Ji Won
AU - Kong, Jin Sun
AU - Lee, Saseong
AU - Yoo, Seung Ah
AU - Koh, Jung Hee
AU - Jin, Jingchun
AU - Kim, Wan Uk
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Angiogenesis and synoviocyte hyperplasia, called ‘pannus,’ are pathologic hallmarks of rheumatoid arthritis (RA). To determine the clinical significance of angiogenic cytokines in RA, the levels of pro-angiogenic cytokines, including VEGF, placenta growth factor (PlGF), and IL-6, were measured in the synovial fluid (SF, n = 54) and sera of RA patients (n = 157) using ELISA. Patients (n = 103) with disease activity score 28 (DAS28) > 3.2, which indicates moderate to high RA activity, underwent follow-up blood sampling at 6 months after treatment with conventional disease-modifying anti-rheumatic drugs (c-DMARD) or biologic DMARD (b-DMARD) including an anti-TNFα antibody, an anti-IL-6 antibody, and abatacept. Ultrasonography (US) was performed on affected joints to define the synovitis severity at the time of sampling. Consequently, in the SF of RA patients, PlGF and IL-6 levels correlated well with synovitis severity determined by US. In RA sera, VEGF and IL-6 levels were elevated in proportion to synovitis severity, correlating with conventional markers for disease activity, including ESR, CRP, and DAS28. In c-DMARD users (n = 53), serially monitored levels of serum VEGF, IL-6, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) all decreased in good and moderate responders but not in nonresponders. In b-DMARD users (n = 49), only serum VEGF well represented the treatment response, while CRP nonspecifically decreased irrespective of the treatment outcome. By multivariable analysis, serum ΔVEGF, but not ΔESR or ΔCRP, was an independent factor associated with good and moderate responses to DMARD. In summary, the angiogenic cytokines PlGF and VEGF represent the synovitis severity of RA assessed by US. In patients receiving b-DMARD, serum VEGF may be more valuable than CRP in reflecting the treatment response.
AB - Angiogenesis and synoviocyte hyperplasia, called ‘pannus,’ are pathologic hallmarks of rheumatoid arthritis (RA). To determine the clinical significance of angiogenic cytokines in RA, the levels of pro-angiogenic cytokines, including VEGF, placenta growth factor (PlGF), and IL-6, were measured in the synovial fluid (SF, n = 54) and sera of RA patients (n = 157) using ELISA. Patients (n = 103) with disease activity score 28 (DAS28) > 3.2, which indicates moderate to high RA activity, underwent follow-up blood sampling at 6 months after treatment with conventional disease-modifying anti-rheumatic drugs (c-DMARD) or biologic DMARD (b-DMARD) including an anti-TNFα antibody, an anti-IL-6 antibody, and abatacept. Ultrasonography (US) was performed on affected joints to define the synovitis severity at the time of sampling. Consequently, in the SF of RA patients, PlGF and IL-6 levels correlated well with synovitis severity determined by US. In RA sera, VEGF and IL-6 levels were elevated in proportion to synovitis severity, correlating with conventional markers for disease activity, including ESR, CRP, and DAS28. In c-DMARD users (n = 53), serially monitored levels of serum VEGF, IL-6, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) all decreased in good and moderate responders but not in nonresponders. In b-DMARD users (n = 49), only serum VEGF well represented the treatment response, while CRP nonspecifically decreased irrespective of the treatment outcome. By multivariable analysis, serum ΔVEGF, but not ΔESR or ΔCRP, was an independent factor associated with good and moderate responses to DMARD. In summary, the angiogenic cytokines PlGF and VEGF represent the synovitis severity of RA assessed by US. In patients receiving b-DMARD, serum VEGF may be more valuable than CRP in reflecting the treatment response.
UR - http://www.scopus.com/inward/record.url?scp=85085521418&partnerID=8YFLogxK
U2 - 10.1038/s12276-020-0443-8
DO - 10.1038/s12276-020-0443-8
M3 - Article
C2 - 32461558
AN - SCOPUS:85085521418
SN - 1226-3613
VL - 52
SP - 843
EP - 853
JO - Experimental and Molecular Medicine
JF - Experimental and Molecular Medicine
IS - 5
ER -