TY - JOUR
T1 - Siglec-1 expression on monocytes is associated with the interferon signature in juvenile dermatomyositis and can predict treatment response
AU - Lerkvaleekul, Butsabong
AU - Veldkamp, Saskia R
AU - van der Wal, Maria M
AU - Schatorjé, Ellen J H
AU - Kamphuis, Sylvia S M
AU - van den Berg, J Merlijn
AU - Muller, Petra C E Hissink
AU - Armbrust, Wineke
AU - Vastert, Sebastiaan J
AU - Wienke, Judith
AU - Jansen, Marc H A
AU - van Royen-Kerkhof, Annet
AU - van Wijk, Femke
N1 - Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press on behalf of the British Society for Rheumatology.
PY - 2022/5/5
Y1 - 2022/5/5
N2 - OBJECTIVE: JDM is a rare chronic immune-mediated inflammatory disease with a predominant role for type I IFN responses. We aimed to determine the potential of Siglec-1 expression on monocytes as a novel IFN-inducible biomarker for disease activity monitoring and prediction of treatment response in patients with JDM. METHODS: Siglec-1 was measured by flow cytometry on circulating monocytes of 21 newly diagnosed JDM patients before start of treatment and, for 10 of these, also during follow-up. The expression levels of five type I IFN-stimulated genes, MX1, IFI44, IFI44L, LY6E and IFIT3, were measured by RT-qPCR to determine the IFN signature and calculate an IFN score. IFN-inducible plasma proteins CXCL10 and galectin-9 were measured by multiplex immunoassay. RESULTS: Siglec-1 and IFN score were increased in JDM patients compared with controls and correlated with clinical disease activity. Stratification of patients by Siglec-1 expression at diagnosis identified those with high Siglec-1 expression as having a higher risk of requiring treatment intensification within the first 3 months after diagnosis (55% vs 0% of patients, P = 0.01). Siglec-1 expression strongly correlated with plasma levels of previously validated biomarkers CXCL10 (rs = 0.81, P < 0.0001) and galectin-9 (rs = 0.83, P < 0.0001), and was superior to the IFN score in predicting treatment response (area under the curve 0.87 vs 0.53, P = 0.01). CONCLUSION: Siglec-1 on monocytes is a novel IFN-inducible biomarker in JDM that correlates with clinical disease activity and identifies patients at risk for a suboptimal treatment response. Further studies are required to validate these findings and their clinical potential.
AB - OBJECTIVE: JDM is a rare chronic immune-mediated inflammatory disease with a predominant role for type I IFN responses. We aimed to determine the potential of Siglec-1 expression on monocytes as a novel IFN-inducible biomarker for disease activity monitoring and prediction of treatment response in patients with JDM. METHODS: Siglec-1 was measured by flow cytometry on circulating monocytes of 21 newly diagnosed JDM patients before start of treatment and, for 10 of these, also during follow-up. The expression levels of five type I IFN-stimulated genes, MX1, IFI44, IFI44L, LY6E and IFIT3, were measured by RT-qPCR to determine the IFN signature and calculate an IFN score. IFN-inducible plasma proteins CXCL10 and galectin-9 were measured by multiplex immunoassay. RESULTS: Siglec-1 and IFN score were increased in JDM patients compared with controls and correlated with clinical disease activity. Stratification of patients by Siglec-1 expression at diagnosis identified those with high Siglec-1 expression as having a higher risk of requiring treatment intensification within the first 3 months after diagnosis (55% vs 0% of patients, P = 0.01). Siglec-1 expression strongly correlated with plasma levels of previously validated biomarkers CXCL10 (rs = 0.81, P < 0.0001) and galectin-9 (rs = 0.83, P < 0.0001), and was superior to the IFN score in predicting treatment response (area under the curve 0.87 vs 0.53, P = 0.01). CONCLUSION: Siglec-1 on monocytes is a novel IFN-inducible biomarker in JDM that correlates with clinical disease activity and identifies patients at risk for a suboptimal treatment response. Further studies are required to validate these findings and their clinical potential.
KW - Siglec-1
KW - biomarkers
KW - dermatomyositis
KW - disease activity
KW - interferon signature
KW - predictor
UR - http://www.scopus.com/inward/record.url?scp=85129998567&partnerID=8YFLogxK
U2 - 10.1093/rheumatology/keab601
DO - 10.1093/rheumatology/keab601
M3 - Article
C2 - 34387304
SN - 1462-0324
VL - 61
SP - 2144
EP - 2155
JO - Rheumatology (Oxford, England)
JF - Rheumatology (Oxford, England)
IS - 5
ER -