title: Leucine-rich α2-glycoprotein as the acute-phase reactant to detect systemic juvenile idiopathic arthritis disease activity during anti-interleukin-6 blockade therapy: A case series.
abstract: OBJECTIVE
  To assess the role of leucine-rich α2-glycoprotein (LRG) as a biomarker for monitoring systemic juvenile idiopathic arthritis (s-JIA) disease activity during interleukin (IL)-6 blockade treatment.
  
  
  METHODS
  We serially measured serum LRG levels in four s-JIA patients treated with the anti-IL-6 receptor antibody tocilizumab and determined the correlation between clinical symptoms and other inflammatory biomarkers and proinflammatory cytokines, including IL-18, IL-6, neopterin, and tumor necrosis factor-α receptor type I and II. The serum levels of LRG and proinflammatory cytokines were determined using enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Serum LRG levels increased concomitantly with s-JIA disease flare-up and macrophage activation syndrome development. Furthermore, even in the clinically inactive phase, serum LRG levels were well above normal values. There were no correlations between serum LRG levels and indicators of s-JIA disease activity other than aspartate aminotransferase. There were significant positive correlations between serum LRG levels and proinflammatory cytokines.
  
  
  CONCLUSIONS
  Serum LRG levels might be a unique and potential biomarker of s-JIA disease activity during IL-6 blockade treatment.
authors.affiliation: a Department of Pediatrics, School of Medicine , Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University , Kanazawa , Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: b Department of Pediatric Rheumatology , Hyogo Prefectural Kobe Children's Hospital , Kobe , Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Nakagishi
authors.affiliation: a Department of Pediatrics, School of Medicine , Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University , Kanazawa , Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Inoue
authors.affiliation: a Department of Pediatrics, School of Medicine , Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University , Kanazawa , Japan.|b Department of Pediatric Rheumatology , Hyogo Prefectural Kobe Children's Hospital , Kobe , Japan.
authors.forename: Mao
authors.initials: M
authors.lastname: Mizuta
authors.affiliation: a Department of Pediatrics, School of Medicine , Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University , Kanazawa , Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yachie
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis; D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000276:immunology; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000276:immunology; D001171:Arthritis, Juvenile / Q000175:diagnosis / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000032:analysis; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D055501:Macrophage Activation Syndrome / Q000209:etiology / Q000276:immunology; D008297:Male; D062072:Patient Acuity; D015203:Reproducibility of Results; D013223:Statistics as Topic; D000067251:Symptom Flare Up; D000093242:Interleukin-6 Inhibitors
chemical_list: D000209:Acute-Phase Proteins; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; D016207:Cytokines; D006023:Glycoproteins; D000093242:Interleukin-6 Inhibitors; C015246:LRG1 protein, human; C502936:tocilizumab
keywords: Acute-phase reactant; leucine-rich α2-glycoprotein; systemic juvenile idiopathic arthritis; tocilizumab