title: Serum milk fat globule epidermal growth factor 8 elevation may subdivide systemic lupus erythematosus into two pathophysiologically distinct subsets.
abstract: OBJECTIVE
  Impaired clearance of apoptotic cells is a potential trigger of systemic lupus erythematosus (SLE). Milk fat globule epidermal growth factor 8 (MFG-E8) plays an important role in the clearance of dying cells. Previously, we reported serum MFG-E8 was elevated in some SLE patients. Here we further investigated the prevalence of MFG-E8 in active SLE and other autoimmune diseases and also tried to clarify the characteristics of MFG-E8-positive and -negative SLE.
  
  
  METHODS
  Serum MFG-E8 was measured in 40 active non-treated SLE patients, 104 disease controls and 104 healthy controls by ELISA. Clinical characteristics and serum cytokine profiles were compared between MFG-E8-positive and MFG-E8-negative SLE patients.
  
  
  RESULTS
  Prevalence of MFG-E8 was significantly higher in SLE patients (40%) than in various controls (p < 0.05). MFG-E8 level became negative after treatment, and increased again upon relapse. When compared, MFG-E8-positive SLE patients showed higher immune complex (p = 0.021) and lower complement (p = 0.004 for CH50). In contrast, MFG-E8-negative SLE patients tended to show higher CRP (p = 0.094). There was a positive correlation between MFG-E8 level and immune complex level (r s = 0.49, p = 0.049). TNF-α (p = 0.019), IFN-γ (p = 0.031) and IL-10 (p = 0.013) were significantly higher in MFG-E8-positive SLE.
  
  
  CONCLUSIONS
  MFG-E8-positive SLE and -negative SLE may have different clinical features, the one with stronger immunological response and the other with stronger inflammatory response, and those two groups may be two distinct subtypes of SLE driven by different mechanisms. Further, MFG-E8 could be used as a biomarker for diagnosis and monitoring of disease activity in certain SLE patients.
authors.affiliation: 1Department of Rheumatology and Clinical Immunology.
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: K
authors.initials: K
authors.lastname: Ohmura
authors.forename: T
authors.initials: T
authors.lastname: Yokoyama
authors.forename: H
authors.initials: H
authors.lastname: Yoshifuji
authors.forename: N
authors.initials: N
authors.lastname: Yukawa
authors.forename: D
authors.initials: D
authors.lastname: Kawabata
authors.forename: T
authors.initials: T
authors.lastname: Fujii
authors.forename: S
authors.initials: S
authors.lastname: Morita
authors.forename: S
authors.initials: S
authors.lastname: Nagata
authors.forename: T
authors.initials: T
authors.lastname: Mimori
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D008894:Milk Proteins / Q000097:blood*; D012008:Recurrence; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D055815:Young Adult
chemical_list: D000954:Antigens, Surface; D015415:Biomarkers; C098942:MFGE8 protein, human; D008894:Milk Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Systemic lupus erythematosus; apoptosis; milk fat globule epidermal growth factor 8; subset