Beneficial use of serum ferritin and heme oxygenase-1 as biomarkers in adult-onset Still’s disease

A multicenter retrospective study

Yohei Kirino, Yasushi Kawaguchi, Yoshifumi Tada, Hiroshi Tsukamoto, Toshiyuki Ota, Masahiro Iwamoto, Hiroki Takahashi, Kohei Nagasawa, Shuji Takei, Takahiko Horiuchi, Hisae Ichida, Seiji Minota, Atsuhisa Ueda, Akihide Ohta, Yoshiaki Ishigatsubo

Research output: Contribution to journalArticle

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Abstract

Background: 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. Methods: 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. Results: 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 (>819 ng/ml; sensitivity 76.1% and specificity 73.8%), and serum HO-1 (>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 > 30.2 ng/ml, but only 50.0% exceeded serum ferritin >819 ng/ml (p =.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. Conclusion: 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.

Original languageEnglish
Pages (from-to)858-864
Number of pages7
JournalModern Rheumatology
Volume28
Issue number5
DOIs
Publication statusPublished - Sep 3 2018

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Adult-Onset Still's Disease
Heme Oxygenase-1
Ferritins
Multicenter Studies
Retrospective Studies
Biomarkers
Serum
Multivariate Analysis
Sensitivity and Specificity
Systemic Vasculitis
Iron-Deficiency Anemias
Pharyngitis

All Science Journal Classification (ASJC) codes

  • Rheumatology

Cite this

Beneficial use of serum ferritin and heme oxygenase-1 as biomarkers in adult-onset Still’s disease : A multicenter retrospective study. / Kirino, Yohei; Kawaguchi, Yasushi; Tada, Yoshifumi; Tsukamoto, Hiroshi; Ota, Toshiyuki; Iwamoto, Masahiro; Takahashi, Hiroki; Nagasawa, Kohei; Takei, Shuji; Horiuchi, Takahiko; Ichida, Hisae; Minota, Seiji; Ueda, Atsuhisa; Ohta, Akihide; Ishigatsubo, Yoshiaki.

In: Modern Rheumatology, Vol. 28, No. 5, 03.09.2018, p. 858-864.

Research output: Contribution to journalArticle

Kirino, Y, Kawaguchi, Y, Tada, Y, Tsukamoto, H, Ota, T, Iwamoto, M, Takahashi, H, Nagasawa, K, Takei, S, Horiuchi, T, Ichida, H, Minota, S, Ueda, A, Ohta, A & Ishigatsubo, Y 2018, 'Beneficial use of serum ferritin and heme oxygenase-1 as biomarkers in adult-onset Still’s disease: A multicenter retrospective study', Modern Rheumatology, vol. 28, no. 5, pp. 858-864. https://doi.org/10.1080/14397595.2017.1422231
Kirino, Yohei ; Kawaguchi, Yasushi ; Tada, Yoshifumi ; Tsukamoto, Hiroshi ; Ota, Toshiyuki ; Iwamoto, Masahiro ; Takahashi, Hiroki ; Nagasawa, Kohei ; Takei, Shuji ; Horiuchi, Takahiko ; Ichida, Hisae ; Minota, Seiji ; Ueda, Atsuhisa ; Ohta, Akihide ; Ishigatsubo, Yoshiaki. / Beneficial use of serum ferritin and heme oxygenase-1 as biomarkers in adult-onset Still’s disease : A multicenter retrospective study. In: Modern Rheumatology. 2018 ; Vol. 28, No. 5. pp. 858-864.
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T1 - Beneficial use of serum ferritin and heme oxygenase-1 as biomarkers in adult-onset Still’s disease

T2 - A multicenter retrospective study

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AU - Kawaguchi, Yasushi

AU - Tada, Yoshifumi

AU - Tsukamoto, Hiroshi

AU - Ota, Toshiyuki

AU - Iwamoto, Masahiro

AU - Takahashi, Hiroki

AU - Nagasawa, Kohei

AU - Takei, Shuji

AU - Horiuchi, Takahiko

AU - Ichida, Hisae

AU - Minota, Seiji

AU - Ueda, Atsuhisa

AU - Ohta, Akihide

AU - Ishigatsubo, Yoshiaki

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N2 - Background: 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. Methods: 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. Results: 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 (>819 ng/ml; sensitivity 76.1% and specificity 73.8%), and serum HO-1 (>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 > 30.2 ng/ml, but only 50.0% exceeded serum ferritin >819 ng/ml (p =.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. Conclusion: 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.

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