title: Increased IgG on cell-derived plasma microparticles in systemic lupus erythematosus is associated with autoantibodies and complement activation.
abstract: OBJECTIVE
  To quantify immunoglobulin and C1q on circulating cell-derived microparticles (MPs) in patients with systemic lupus erythematosus (SLE) and to determine whether immunoglobulin and C1q levels are correlated with clinical and serologic parameters.
  
  
  METHODS
  Sixty-eight clinically well-characterized SLE patients, 38 healthy controls, 6 patients with systemic sclerosis (SSc), and 6 patients with rheumatoid arthritis (RA) were included. The numbers of annexin V-binding MPs displaying IgG, IgM, or C1q were enumerated by flow cytometry. MP protein levels were determined by mass spectrometry in clinically defined subsets of SLE patients and controls. The MP IgG load was determined by flow cytometric analysis of all samples from SLE patients and healthy controls.
  
  
  RESULTS
  SLE patients had significantly increased total and relative numbers of IgG-positive MPs (P = 0.0004), with a much higher average IgG load per MP (P < 0.0001) than healthy controls. Quantitative mass spectrometry of purified MPs verified significantly increased IgG, IgM, and C1q levels in SLE patients. In RA and SSc patients, the average IgG load per MP was significantly lower than in SLE patients (P = 0.006 and P = 0.05, respectively). Also, the IgM load and C1q load per MP were significantly higher in SLE patients than in the control groups (P < 0.05), except for IgM in the RA group. IgG-positive MPs were significantly associated with the presence of anti-double-stranded DNA, anti-extractable nuclear antigen, and antihistone antibodies, with total IgG, and with decreased leukocyte counts. Average IgG load per MP was associated with lower concentrations of MPs, the presence of anti-C1q antibodies, and complement consumption.
  
  
  CONCLUSIONS
  Our findings indicate that circulating cell-derived MPs in SLE patients carry increased loads of IgG, IgM, and C1q and that IgG MPs are associated with autoantibodies and complement activation. The findings link immunologic reactions on MPs with the etiology of SLE.
authors.affiliation: Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Christoffer T
authors.initials: CT
authors.lastname: Nielsen
authors.forename: Ole
authors.initials: O
authors.lastname: Østergaard
authors.forename: Line
authors.initials: L
authors.lastname: Stener
authors.forename: Line V
authors.initials: LV
authors.lastname: Iversen
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.forename: Birgitta
authors.initials: B
authors.lastname: Gullstrand
authors.forename: Søren
authors.initials: S
authors.lastname: Jacobsen
authors.forename: Niels H H
authors.initials: NH
authors.lastname: Heegaard
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D055252:Cell-Derived Microparticles / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G