Milk fat globule epidermal growth factor 8 (MFG-E8) on monocytes is a novel biomarker of disease activity in systemic lupus erythematosus

Mari Ushikubo, Shuntaro Saito, Jun Kikuchi, Masaru Takeshita, Keiko Yoshimoto, Hidekata Yasuoka, Kunihiro Yamaoka, Noriyasu Seki, Katsuya Suzuki, Hisaji Oshima, Tsutomu Takeuchi

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Milk fat globule epidermal growth factor (MFG-E8) is related secreted protein which links phosphatidylserine on apoptotic cells and integrin αvβ3/5 on phagocytes. To clarify the clinical significance of MFG-E8 in SLE, we analyzed the correlation between expression level of MFG-E8 in circulating phagocytic leukocytes and clinical parameters of patients. Methods: The study was conducted under a multi-center, prospective cohort design. Patients with one or both BILAG A or B, or SLEDAI- 2 K ≥ 4 with clinical symptoms were defined as the active SLE group. Expression of MFG-E8 on monocytes and concentration in serum were measured by FACS and ELISA, respectively. Results: 96 subjects were enrolled. The absolute number and proportion of MFG-E8-positive monocytes to total monocytes were significantly higher in the active SLE group (p < 0.01). Importantly, the proportion was also significantly correlated with SLEDAI-2K, clinical SLEDAI, as well as serum levels of anti-ds-DNA antibody and complement and C1q. In addition, the proportion of MFG-E8-positive monocytes to total monocytes was significantly decreased from baseline in active SLE patients after 6 months’ treatment and increased concordantly with disease activity in 6 refractory cases. Further, in receiver operating characteristic curve analysis for discrimination between active and inactive SLE, the AUC of the proportion of MFG-E8 was 0.854, which was equivalent to classical activity markers such as anti-ds DNA antibody (0.776), complement (0.897) and C1q (0.815) Conclusions: The proportion of MFG-E8-positive monocytes to total monocytes in peripheral blood was positively associated with disease activity in SLE and may be a novel biomarker of disease activity.

Original languageEnglish
Pages (from-to)61-69
Number of pages9
JournalLupus
Volume30
Issue number1
DOIs
Publication statusPublished - 2021 Jan

Keywords

  • Milk fat globule epidermal growth factor 8 (MFG-E8)
  • biomarker
  • monocyte
  • systemic lupus erythematosus

ASJC Scopus subject areas

  • Rheumatology

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