Beneficial use of serum ferritin and heme oxygenase-1 as biomarkers in adult-onset Still’s disease: A multicenter retrospective study
Creators: name: Kirino, Yohei
name: Kawaguchi, Yasushi
name: Tada, Yoshifumi
name: Tsukamoto, Hiroshi
name: Ota, Toshiyuki
name: Iwamoto, Masahiro
name: Takahashi, Hiroki
name: Nagasawa, Kohei
name: Takei, Shuji
name: Horiuchi, Takahiko
name: Ichida, Hisae
name: Minota, Seiji
name: Ueda, Atsuhisa
name: Akihide Ohta
name: Ishigatsubo, Yoshiaki
Publisher: name: Taylor & Francis
Year: 2018
Subjects: subject: Biochemistry
subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Cell Biology
subject: Genetics
subject: Biotechnology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: FOS: Chemical sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: 19999 Mathematical Sciences not elsewhere classified
subject: FOS: Mathematics
subject: FOS: Mathematics
subject: Cancer
subject: Science Policy
subject: Hematology

description: <b>Background:</b> Heme oxygenase (HO)-1 is a heme-degrading enzyme highly expressed in monocyte/macrophage, serum levels of which may be promising biomarker for adult-onset Still’s disease (AOSD). We here report data on the use of serum ferritin and HO-1 levels in AOSD. <b>Methods:</b> Under the Hypercytokinemia Study Group collaboration, we collected sera from a total of 145 AOSD patients. Three independent experts judged whether the patients were definite AOSD depending on the clinical information. These 91 ‘definite AOSD’ patients were further divided into active, remission, and relapse groups. Forty-six cases of systemic vasculitis, sepsis, etc. were included as disease controls. Serum ferritin and HO-1 levels were measured using ELISA. Associations between clinical symptoms, serum ferritin, and HO-1 were explored. Multivariate regression analysis was performed to identify independent variables associated with definite AOSD diagnosis. <b>Results:</b> Serum ferritin and HO-1 levels were significantly higher in active and relapsed AOSD cases compared to disease controls, and were reduced by the treatment. Although a significant correlation was found between serum ferritin and HO-1 levels, a discrepancy was found in some cases such as iron-deficiency anemia. Receiver operating characteristic analysis identified optimal levels of serum ferritin (&gt;819 ng/ml; sensitivity 76.1% and specificity 73.8%), and serum HO-1 (&gt;30.2 ng/ml; sensitivity 84.8% and specificity 83.3%) that differentiated AOSD from controls. Interestingly, 88.9% of patients with AOSD who relapsed exceeded the cut-off value of serum HO-1 &gt; 30.2 ng/ml, but only 50.0% exceeded serum ferritin &gt;819 ng/ml (<i>p</i> = .013), suggesting that serum HO-1 levels may be a convenient indicator of AOSD disease status. Multivariate analysis identified neutrophilia, RF/ANA negativity, sore throat, and elevated serum HO-1 as independent variables associated with AOSD diagnosis. <b>Conclusion:</b> We confirmed that serum ferritin and HO-1 serve as highly specific and sensitive biomarkers for AOSD. A future prospective study with large sample size is necessary to determine whether these biomarkers could be included in Yamaguchi’s Criteria.