FRI0282 Milk fat globule epidermal growth factor 8 on monocytes is a novel biomarker of disease activity in systemic lupus erythematosus
Authors: M. Ushikubo, S. Saito, J. Kikuchi, M. Takeshita, K. Yoshimoto, H. Yasuoka, K. Yamaoka, N. Seki, K. Suzuki, H. Oshima, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Milk fat globule epidermal growth factor 8 (MFG-E8) is an apoptosis-related secreted protein. It has been reported that MFG-E8 deficient or excess mice developed a systemic lupus erythematosus (SLE)-like autoimmune disease due to impaired clearance of apoptotic cells,<sup>1</sup> suggenting that abnormal expression of MFG-E8 is involved in the pathogenesis of SLE. Since elevated serum MFG-E8 level has been found in SLE patients,<sup>2</sup> it may possibly provide the classification of the disease by pathological conditions.<sup>3</sup> However, the assosiation with MFG-E8 expression and clinical features of SLE patients is not fully understood. <h3>Objectives</h3> To clarify the clinical significance of MFG-E8 in SLE, we analysed the correlation between the expression level of MFG-E8 in circulating phagocytic leukocytes and clinical parameters of the patients. <h3>Methods</h3> A multi-centre, exploratory and prospective SLE cohort was established. Among SLE patients who visited our division from May 2015 to <sup>March 2017</sup> and satisfied the 1997 revised criteria, patients with one or both of BILAG A or B, or with SLEDAI-2K≥4 and clinical symptoms were defined as active SLE. These patients were then matched with randomly selected patients by age, gender, history of nephritis, and daily glucocorticoid dose as an inactive SLE group. Age and sex matched healthy controls (HC) were also recruited. The expression level of MFG-E8 in monocytes and its concentration in serum of the patients were measured by FACS and ELISA, respectively. The clinical parameters of the patients were collected from their clinical records. <h3>Results</h3> A total of 108 cases were enrolled, consisting of 36 active (mean age: 44.2±18.6, female: 80.6%, nephritis: 69.7%), 38 inactive SLE and 24 HC cases. The absolute number and the proportion of MFG-E8 positive-monocytes to total monocytes were significantly higher in the active SLE group (p&lt;0.01), whereas serum MFG-E8 level showed no significant difference among the group. Importantly, the proportion was also significantly correlated with SLEDAI-2K, serum levels of anti-ds-DNA antibody and complement and C1q (table 1). Nortably, elevated proportion of MFG-E8-positive monocytes to total monocytes was observed in the patients with cutaneous or musculoskeletal involvement or leukocytopenia. In addition, the proportion of MFG-E8-positive monocytes to total monocytes significantly decreased from the baseline in active SLE patients after 6 months treatment and increased concordantly with disease activity in 6 refractory cases. Then we further analysed the accuracy to discriminate between active and inactive SLE patients and found that the proportion of MFG-E8 monocytes showed significant accuracy of disease activity, which is equivalent to serum levels of anti-ds-DNA antibody, complement and C1q, by receiver operating characteristic curve analysis (figure 1). <h3>Conclusions</h3> Our study indicate that the proportion of MFG-E8-positive monocytes to total monocyte in peripheral blood was positively associated with disease activity of SLE and may be a novel mechanistic biomarker to determine the disease activity. <h3>References</h3> [1] Science2004;304(5674):1147–50. [2] J Leuko Biol. 2008;83:1300–7. [3] Lupus2014;23:386–94. <h3>Disclosure of Interest</h3> None declared