CONCISE COMMUNICATION Serum interleukin-34 levels in patients with systemic sclerosis: Clinical association with interstitial lung disease Ai KUZUMI, Ayumi YOSHIZAKI, Satoshi TOYAMA, Takemichi FUKASAWA, Satoshi EBATA, Kouki NAKAMURA, Takashi YAMASHITA, Ryosuke SAIGUSA, Shunsuke MIURA, Megumi HIRABAYASHI, Asako YOSHIZAKI, Yoshihide ASANO, Shinichi SATO Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan ABSTRACT Interleukin (IL)-34 is a hematopoietic cytokine promoting proliferation and differentiation of macrophages. Because abnormal activation of macrophages is involved in the development of systemic sclerosis (SSc), we investigated serum IL-34 levels in patients with SSc. Serum IL-34 levels were significantly increased in diffuse cutaneous SSc compared with limited cutaneous SSc and healthy controls, while there were no significant differ- ences between limited cutaneous SSc and healthy controls. In addition, SSc patients with increased serum IL-34 levels more often had interstitial lung disease (ILD) than those with normal levels. Moreover, in SSc patients, serum IL-34 levels negatively correlated with the percentage of predicted vital capacity, while they positively cor- related with ground-glass opacity score and fibrotic score on chest computed tomography. Collectively, increased serum IL-34 levels were associated with greater frequency and severity of ILD in SSc patients. Serum IL-34 levels may be a useful serological marker for SSc-associated ILD. Key words: fibrosis, interleukin-34, interstitial lung disease, macrophage, systemic sclerosis. INTRODUCTION Systemic sclerosis (SSc) is a connective tissue disease charac- terized by excessive fibrosis of the skin, lung and other internal organs. Although the pathogenesis of SSc still remains elusive, abnormal activation of immune cells has been identified in SSc, indicating the autoimmune nature of the disease. 1 Previ- ous studies have shown that macrophages are polarized toward a profibrotic phenotype in the skin and peripheral blood of SSc patients. 2 Furthermore, there is evidence showing that profibrotic macrophages are involved in the development of interstitial lung disease (ILD) in SSc. 3 Interleukin (IL)-34 is a hematopoietic cytokine which was identified in 2008 as the second ligand of colony-stimulating factor 1 receptor, in addition to the already well-known ligand, macrophage colony-stimulating factor. 4 IL-34 pro- motes survival, proliferation and differentiation of monocytes and macrophages. IL-34, which is secreted by keratinocytes, can be detected at mRNA level in various organs such as lungs, liver and spleen under physiological conditions. Impor- tantly, IL-34 is induced at protein level under inflammatory conditions including autoimmune diseases. Indeed, several studies have shown that serum IL-34 levels are increased in rheumatoid arthritis and systemic lupus erythematosus. 5,6 Furthermore, recent studies have demonstrated that IL-34 promotes the differentiation of monocytes into profibrotic macrophages. 7 Consistent with this, serum IL-34 levels cor- relate with the severity of liver fibrosis in patients with chronic hepatitis C, where macrophages acquire profibrotic properties. 8 However, any association of IL-34 with SSc has not been previously investigated. In this study, we examined serum IL-34 levels and their clinical correlations in SSc patients. CASE REPORT Patients Serum samples were obtained from 58 SSc patients (52 women, six men; median, age [25–75th percentiles], 43 years [37.5–47]; disease duration, 3 years [1–8]) and 20 healthy con- trols (18 women, two men; age, 39.5 years [33.8–46]) after get- ting written informed consent. Patients treated with corticosteroids or other immunosuppressants prior to their first visits were excluded. SSc patients were categorized by LeR- oy’s classification system: 9 43 diffuse cutaneous SSc (dcSSc) patients (age, 43 years [36.5–49]; disease duration, 3 years [1– 8]) and 15 limited cutaneous SSc (lcSSc) patients (age, 44 years [39.5–44.5]; disease duration, 2 years [1–7.5]). The whole study was approved by the ethics committee of the University of Tokyo Graduate School of Medicine. Correspondence: Ayumi Yoshizaki, M.D., Ph.D., Department of Dermatology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Email: ayuyoshi@me.com Received 26 April 2018; accepted 11 June 2018. 1 © 2018 Japanese Dermatological Association doi: 10.1111/1346-8138.14538 Journal of Dermatology 2018; : 1–5