Serum Interferon-α Is a Biomarker To Reflect The Disease Activity In Patients With Anti-Melanoma Differentiation-Associated Gene 5 (MDA5) Antibody-Positive Dermatomyositis

Yoshiro Horai¹, Tomohiro Koga², Keita Fujikawa³, Ayuko Takatani⁴, Ayako Nishino¹, Yoshikazu Nakashima⁵, Takahisa Suzuki⁵, Shin-ya Kawashiri¹, Naoki Iwamoto⁵, Kunihiro Ichinose⁶, Mami Tamai⁵, Hideki Nakamura⁵, Hiroaki Ida⁷, Yuji Ishimatsu⁸, Hiroshi Mukae⁹, Yasuhito Hamaguchi¹⁰, Manabu Fujimoto¹¹, Masataka Kuwana¹², Tomoki Origuchi¹³, Shigeru Kohno⁸ and Atsushi Kawakami⁵, ¹Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ²Departments of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ³Arthritis and Connective Tissue Disease, Isahaya Health Insurance General Hospital, Isahaya, Japan, ⁴Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ⁵Unit of Translational Medicine, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ⁶Department of Immunology and Rheumatology, Unit of Translational Medicine, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ⁷Department of Internal Medicine, Division of REspirology, Neurology and Rheumatology, Kurume University School of Medicine, Kurume, Japan, ⁸Department of Molecular Microbiology and Immunology, Nagasaki University School of Medicine, Nagasaki, Japan, Nagasaki, Japan, ⁹Department of Respiratory Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan, Kitakyushu, Japan, ¹⁰Department of Dermatology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan, ¹¹Dermatology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan, ¹²Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, ¹³Department of Health Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Amyopathic dermatomyositis

Session Information

Title: Muscle Biology, Myositis and Myopathies: Advances in the Epidemiology, Immunology and Therapy of Myositis

Session Type: Abstract Submissions (ACR)

Background/Purpose: The pathogenesis of anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-positive dermatomyositis (DM), which often complicates rapidly progressive interstitial lung disease (RPILD), is thought to be associated with double-stranded RNA virus infection. Some serum factors, including interferon-a (IFN-a), are found to be elevated in these patients. Recent investigations have reported that high serum ferritin and the titer of anti-MDA5 Ab are poor prognosis factors in patients with anti-MDA5 Ab-positive DM. The aim of this study is to clarify the clinical importance of measurement of serum type I IFNs in patients with anti-MDA5 Ab-positive DM.

Methods: The study population consisted of 30 patients (22 females and 8 males) with DM: Ten patients were anti-MDA5 Ab-positive whereas the remaining 20 were anti-MDA5 Ab-negative, respectively. All of the 10 anti-MDA5 Ab-positive sera were also positive with anti-clinically amyopathic dermatomyositis (CADM) 140kDa polypeptide Abs detected by immunoprecipitation assay. Clinical diagnosis of DM was made by either Sontheimer’s criteria for CADM or Bohan and Peter’s criteria for classical DM. Serum IFN-a, IFN-b, interleukin 18 (IL-18), ferritin and the titer of anti-MDA5 Ab at initial visit were measured by each enzyme-linked immunosorbent assay (ELISA). Clinical characteristics, such as the diagnosis of CADM or classical DM and the presence of RPILD, were confirmed by medical records and the associations of IFNs with the other variables were examined. All of the patients gave their informed consent to be subjected to the protocol that was approved by the Institutional Review Board of Nagasaki University.

Results: Eleven patients were diagnosed as CADM whereas the remaining 19 patients as classical DM, respectively. RPILD was confirmed in 10 patients. The presence of CADM and RPILD as well as serum concentrations of IFN-a and ferritin were significantly higher in anti-MDA5 Ab-positive DM patients as compared with anti-MDA5 Ab-negative DM patients. However, there was no difference in serum concentrations of IFN-b and IL-18 between the two patients groups. Furthermore, clear positive correlations were found between IFN-a and the titer of anti-MDA5 Ab (r = 0.54, p = 0.0037) and between IFN-a and ferritin (r = 0.49, p = 0.0086), respectively.

Conclusion: Serum IFN-α level is high in anti-MDA5 Ab-positive DM patients presenting clinical characteristics with CADM and RPILD. Considering good correlations of IFN-a with the titer of MDA5 Ab and ferritin, serum IFN-α is considered as a biomarker to reflect the disease activity in patients with anti-MDA5 Ab-positive DM.

Disclosure:

Y. Horai,
None;

T. Koga,
None;

K. Fujikawa,
None;

A. Takatani,
None;

A. Nishino,
None;

Y. Nakashima,
None;

T. Suzuki,
None;

S. Y. Kawashiri,
None;

N. Iwamoto,
None;

K. Ichinose,
None;

M. Tamai,
None;

H. Nakamura,
None;

H. Ida,
None;

Y. Ishimatsu,
None;

H. Mukae,
None;

Y. Hamaguchi,
None;

M. Fujimoto,
None;

M. Kuwana,
None;

T. Origuchi,
None;

S. Kohno,
None;

A. Kawakami,
None.

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