title: Improved monitoring of clinical response in Systemic Lupus Erythematosus by longitudinal trend in soluble vascular cell adhesion molecule-1.
abstract: BACKGROUND
  To determine whether optimal use of serial measurements of serum levels of soluble cell adhesion molecules (CAM) can improve monitoring of disease activity in SLE.
  
  
  METHODS
  Serum levels of soluble CAM and conventional SLE biomarkers were measured in serial samples (n = 80) from 21 SLE patients during and after flare and correlated in longitudinal analysis with disease activity determined by ECLAM score. Blood samples from a second cohort of 34 SLE patients were subject to flow cytometry to correlate serum biomarkers with B cell subsets.
  
  
  RESULTS
  By adjusting for the baseline level (at the first visit), delta soluble vascular cell adhesion molecule-1 (sVCAM-1) showed stronger correlation with changes in ECLAM score and improved sensitivity and specificity for identifying SLE responders versus non-responders compared to conventional SLE biomarkers including anti-dsDNA antibody titre and complement C3. Multiple regression analysis identified delta sVCAM-1 as the best marker of SLE clinical response. sVCAM-1 levels were significantly correlated with CD95(+)CD27(+) activated memory B cells, CD95(+) plasmablasts and circulating plasma cell numbers in SLE patients.
  
  
  CONCLUSIONS
  Subtracting a baseline level of sVCAM-1 for each individual substantially improved its utility as a biomarker. Delta sVCAM-1 was superior to conventional SLE biomarkers for monitoring changes in disease activity. This suggests that serial monitoring of serum sVCAM-1 trends should be considered in SLE patients to document responses to treatment. We hypothesise that the correlation between activated B cell subsets and circulating plasma cell numbers with soluble VCAM-1 serum levels in SLE may relate to the important role of VCAM-1 in B lymphocyte survival and maturation in bone marrow and secondary lymphoid tissues.
authors.affiliation: Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK. myles.lewis@qmul.ac.uk.
authors.forename: Myles J
authors.initials: MJ
authors.lastname: Lewis
authors.affiliation: Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK. s.vyse@qmul.ac.uk.
authors.forename: Simon
authors.initials: S
authors.lastname: Vyse
authors.affiliation: Department of Medical and Molecular Genetics, King's College London, London, SE1 9RT, UK. adrianshields@doctors.org.uk.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Shields
authors.affiliation: Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK. lu.zou@qmul.ac.uk.
authors.forename: Lu
authors.initials: L
authors.lastname: Zou
authors.affiliation: Lupus Research Laboratory, The Rayne Institute, King's College London, St Thomas' Hospital, London, SE1 7EH, UK. munther.khamashta@kcl.ac.uk.
authors.forename: Munther
authors.initials: M
authors.lastname: Khamashta
authors.affiliation: Rheumatology Department, King's College Hospital, London, SE5 9RS, UK. patrick.gordon2@nhs.net.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Gordon
authors.affiliation: Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK. c.pitzalis@qmul.ac.uk.
authors.forename: Costantino
authors.initials: C
authors.lastname: Pitzalis
authors.affiliation: Department of Medical and Molecular Genetics, King's College London, London, SE1 9RT, UK. tim.vyse@kcl.ac.uk.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Vyse
authors.affiliation: Lupus Research Laboratory, The Rayne Institute, King's College London, St Thomas' Hospital, London, SE1 7EH, UK. david.d'cruz@kcl.ac.uk.
authors.forename: David P
authors.initials: DP
authors.lastname: D'Cruz
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000175:diagnosis* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods / Q000639:trends; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D019010:Vascular Cell Adhesion Molecule-1