Galectin-9 and CXCL10 as Biomarkers for Disease Activity in Juvenile Dermatomyositis: A Longitudinal Cohort Study and Multicohort Validation.
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Wienke Judith, Bellutti Enders Felicitas, Lim Johan, Mertens Jorre S, van den Hoogen Luuk L, Wijngaarde Camiel A, Yeo Joo Guan, Meyer Alain, Otten Henny G, Fritsch-Stork Ruth D E, Kamphuis Sylvia S M, Hoppenreijs Esther P A H, Armbrust Wineke, van den Berg J Merlijn, Hissink Muller Petra C E, Tekstra Janneke, Hoogendijk Jessica E, Deakin Claire T, de Jager Wilco, van Roon Joël A G, van der Pol W Ludo, Nistala Kiran, Pilkington Clarissa, de Visser Marianne, Arkachaisri Thaschawee, Radstake Timothy R D J, van der Kooi Anneke J, Nierkens Stefan, Wedderburn Lucy R, van Royen-Kerkhof Annet, van Wijk Femke
Аннотация
METHODS: Levels of galectin-9 and CXCL10 were measured by multiplex immunoassay in serum samples from 125 unique patients with juvenile DM in 3 international cross-sectional cohorts and a local longitudinal cohort. The disease specificity of both proteins was examined in 50 adult patients with DM or nonspecific myositis (NSM) and 61 patients with other systemic autoimmune diseases.
RESULTS: Both cross-sectionally and longitudinally, galectin-9 and CXCL10 outperformed the currently used laboratory marker, creatine kinase (CK), in distinguishing between juvenile DM patients with active disease and those in remission (area under the receiver operating characteristic curve [AUC] 0.86-0.90 for galectin-9 and CXCL10; AUC 0.66-0.68 for CK). The sensitivity and specificity for active disease in juvenile DM was 0.84 and 0.92, respectively, for galectin-9 and 0.87 and 1.00, respectively, for CXCL10. In 10 patients with juvenile DM who experienced a flare and were prospectively followed up, continuously elevated or rising biomarker levels suggested an imminent flare up to several months before the onset of symptoms, even in the absence of elevated CK levels. Galectin-9 and CXCL10 distinguished between active disease and remission in adult patients with DM or NSM (P = 0.0126 for galectin-9 and P < 0.0001 for CXCL10) and were suited for measurement in minimally invasive dried blood spots (healthy controls versus juvenile DM, P = 0.0040 for galectin-9 and P < 0.0001 for CXCL10).
CONCLUSION: In this study, galectin-9 and CXCL10 were validated as sensitive and reliable biomarkers for disease activity in juvenile DM. Implementation of these biomarkers into clinical practice as tools to monitor disease activity and guide treatment might facilitate personalized treatment strategies.