TY - JOUR
T1 - The identification of CCL18 as biomarker of disease activity in localized scleroderma
AU - Mertens, J. S.
AU - de Jong, E. M.G.J.
AU - van den Hoogen, L. L.
AU - Wienke, J.
AU - Thurlings, R. M.
AU - Seyger, M. M.B.
AU - Hoppenreijs, E. P.A.H.
AU - Wijngaarde, C. A.
AU - van Vlijmen-Willems, I. M.J.J.
AU - van den Bogaard, E.
AU - Giovannone, B.
AU - van Wijk, F.
AU - van Royen-Kerkhof, A.
AU - Marut, W.
AU - Radstake, T. R.D.
N1 - Copyright © 2019. Published by Elsevier Ltd.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Background: Localized Scleroderma (LoS) encompasses a group of idiopathic skin conditions characterized by (sub)cutaneous inflammation and subsequent development of fibrosis. Currently, lack of accurate tools enabling disease activity assessment leads to suboptimal treatment approaches. Objective: To investigate serum concentrations of cytokines and chemokines implicated in inflammation and angiogenesis in LoS and explore their potential to be utilized as biomarker of disease activity. Additionally, to investigate the implication of potential biomarkers in disease pathogenesis. Methods: A 39-plex Luminex immuno-assay was performed in serum samples of 74 LoS and 22 Healthy Controls. The relation between a validated clinical measure of disease activity (mLoSSI) and serum analytes was investigated. Additionally, gene and protein expression were investigated in circulating cells and skin biopsies. Results: From the total of 39, 10 analytes (CCL18, CXCL9, CXCL10, CXCL13, TNFRII, Galectin-9, TIE-1, sVCAM, IL-18, CCL19) were elevated in LoS serum. Cluster analysis of serum samples revealed CCL18 as most important analyte to discriminate between active and inactive disease. At individual patient level, CCL18 serum levels correlated strongest with mLoSSI-scores (rs = 0.4604, P < 0.0001) and in longitudinal measures CCL18 concentrations normalised with declining disease activity upon treatment initiation. Additionally, CCL18 was elevated in LoS serum, and not in (juvenile) dermatomyositis or spinal muscular atrophy. Importantly, CCL18 gene and protein expression was increased at the inflammatory border of cutaneous LoS lesions, with normal expression in unaffected skin and circulating immune cells. Conclusion: CCL18 is specific for disease activity in LoS thereby providing relevance as a biomarker for this debilitating disease.
AB - Background: Localized Scleroderma (LoS) encompasses a group of idiopathic skin conditions characterized by (sub)cutaneous inflammation and subsequent development of fibrosis. Currently, lack of accurate tools enabling disease activity assessment leads to suboptimal treatment approaches. Objective: To investigate serum concentrations of cytokines and chemokines implicated in inflammation and angiogenesis in LoS and explore their potential to be utilized as biomarker of disease activity. Additionally, to investigate the implication of potential biomarkers in disease pathogenesis. Methods: A 39-plex Luminex immuno-assay was performed in serum samples of 74 LoS and 22 Healthy Controls. The relation between a validated clinical measure of disease activity (mLoSSI) and serum analytes was investigated. Additionally, gene and protein expression were investigated in circulating cells and skin biopsies. Results: From the total of 39, 10 analytes (CCL18, CXCL9, CXCL10, CXCL13, TNFRII, Galectin-9, TIE-1, sVCAM, IL-18, CCL19) were elevated in LoS serum. Cluster analysis of serum samples revealed CCL18 as most important analyte to discriminate between active and inactive disease. At individual patient level, CCL18 serum levels correlated strongest with mLoSSI-scores (rs = 0.4604, P < 0.0001) and in longitudinal measures CCL18 concentrations normalised with declining disease activity upon treatment initiation. Additionally, CCL18 was elevated in LoS serum, and not in (juvenile) dermatomyositis or spinal muscular atrophy. Importantly, CCL18 gene and protein expression was increased at the inflammatory border of cutaneous LoS lesions, with normal expression in unaffected skin and circulating immune cells. Conclusion: CCL18 is specific for disease activity in LoS thereby providing relevance as a biomarker for this debilitating disease.
KW - Biomarker
KW - CCL18
KW - Chemokine
KW - Cytokine
KW - Eosinophilic fasciitis
KW - Localized scleroderma
KW - Morphea
KW - Pulmonary and activation-regulated chemokine (PARC)
KW - Shullman syndrome
KW - Skin serum
UR - http://www.scopus.com/inward/record.url?scp=85066833058&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2019.04.008
DO - 10.1016/j.jaut.2019.04.008
M3 - Article
C2 - 31006523
AN - SCOPUS:85066833058
SN - 0896-8411
VL - 101
SP - 86
EP - 93
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
ER -