Use of Serum Ferritin and Heme Oxygenase 1 for the Diagnosis of Adult-Onset Still's Disease: A Preliminary Report of Multicenter Study

Yohei Kirino¹, Yasushi Kawaguchi², Yoshifumi Tada³, Seiji Minota⁴, Toshiyuki Ota⁵, Kohei Nagasawa⁶, Hiroshi Tsukamoto⁷, Syuji Takei^8,9, Takahiko Horiuchi¹⁰, Hiroki Takahashi¹¹, Hisae Ichida², Masahiro Iwamoto⁴, Atsuhisa Ueda¹, Akihide Ohta¹², Yoshiaki Ishigatsubo^1,13 and Hypercytokinemia Study Group, ¹Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan, ²Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, ³Department of Internal Medicine, Division of Rheumatology, Saga University, Saga, Japan, ⁴Department of Internal Medicine, Division of Rheumatology/Clinical Immunology, Jichi Medical University, Shimotsuke, Japan, ⁵Department of Rheumatology, Iizuka Hospital, Iizuka, Japan, ⁶Rheumatic Disease Center, Sawara Hospital, Fukuoka, Japan, ⁷First Dept of Internal Med, Kyushu University, Fukuoka, Japan, ⁸School of Health Sciences, Faculty of Medicine,, Kagoshima University, Kagoshima City, Japan, ⁹School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima, Japan, ¹⁰Department of Internal Medicine, Kyushu University Beppu Hospital, Beppu, Japan, ¹¹epartment of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan, ¹²Department of Adult and Gerontological Nursing, Saga University School of Medicine, Saga, Japan, ¹³Yokosuka Rheumatic Diseases Center, Yokosuka City Hospital, Yokosuka, Japan

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Adult-onset Still's disease, Autoinflammation, biomarkers and diagnosis

Session Information

Date: Sunday, November 8, 2015

Session Title: Miscellaneous Rheumatic and Inflammatory Diseases Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Yamaguchi’s criteria
for classification of adult-onset Still’s disease (AOSD) has been widely
applied in clinic despite it was established decades ago. However,
hyperferritinemia, which is a hallmark of AOSD, is not included in the
criteria. Moreover, the criteria require differential diagnosis of malignancy,
infection, etc., which has been challenging. Heme oxygenase (HO)-1 is
stress-inducible heme degrading enzyme highly expressed in monocyte/macrophage,
serum levels of which has been reported as a promising biomarker for AOSD.
We here report preliminary data on serum ferritin and HO-1 levels and AOSD
disease activity.

Methods: Under the Hypercytokinemia Study Group
collaboration, we collected sera from a total of 111 AOSD cases. Those patients
were further divided into active, remission, and relapse groups, based on their
clinical status. Other rheumatic diseases such as ANCA-associated
vasculitis, and culture-positive sepsis were included as disease controls.
Serum ferritin and HO-1 levels were measured in all of the collected samples by
means of ELISA. An association among clinical symptoms, serum ferritin, and
HO-1 was explored.

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 significant
correlation between serum ferritin and HO-1 levels were observed, there were
some discrepancies. After remission-induction therapy, 72.2% of the patients’ serum
ferritin levels were normalized, but 61.1% of them had high serum HO-1 levels
(>13.8 ng/ml). Moreover, 31% of patients in remission exhibited high HO-1
levels, but high ferritin levels were observed only in 6.9% of the patients
(figure).

Conclusion: We confirmed that serum
ferritin and HO-1 serve as a biomarker for AOSD. Characterization of serum ferritin
and HO-1 levels in AOSD disease status merit further investigation. By
enrolling more cases and disease controls, we plan to determine use of ferritin
and HO-1 for the diagnosis of AOSD (UMIN000012912).

Disclosure: Y. Kirino, None; Y. Kawaguchi, None; Y. Tada, None; S. Minota, Astellas, 2,Pfizer Inc, 2,Essai, 2,AbbVie, 2,Mitsubishi-Tanabe, 2,Takeda, 2,Chugai, 7; T. Ota, None; K. Nagasawa, None; H. Tsukamoto, None; S. Takei, None; T. Horiuchi, None; H. Takahashi, None; H. Ichida, None; M. Iwamoto, Astellas Pharma, 8,Takeda Phamaceutical, 8; A. Ueda, None; A. Ohta, None; Y. Ishigatsubo, None.

To cite this abstract in AMA style:

Kirino Y, Kawaguchi Y, Tada Y, Minota S, Ota T, Nagasawa K, Tsukamoto H, Takei S, Horiuchi T, Takahashi H, Ichida H, Iwamoto M, Ueda A, Ohta A, Ishigatsubo Y. Use of Serum Ferritin and Heme Oxygenase 1 for the Diagnosis of Adult-Onset Still’s Disease: A Preliminary Report of Multicenter Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/use-of-serum-ferritin-and-heme-oxygenase-1-for-the-diagnosis-of-adult-onset-stills-disease-a-preliminary-report-of-multicenter-study/. Accessed March 21, 2023.

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