Improved monitoring of clinical response in Systemic Lupus Erythematosus by longitudinal trend in soluble vascular cell adhesion molecule-1

Myles J Lewis*, Simon Vyse, Adrian M. Shields, Lu Zou, Munther Khamashta, Patrick A. Gordon, Costantino Pitzalis, Timothy J. Vyse, David P. D'Cruz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)
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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. Conclusion: 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.

Original languageEnglish
Article number5
JournalArthritis Research and Therapy
Volume18
Issue number1
DOIs
Publication statusPublished - 8 Jan 2016

Keywords

  • Anti-double-stranded DNA antibodies
  • Biomarker
  • CD95
  • Complement C3
  • Memory B cells
  • Plasma cells
  • Plasmablasts
  • Soluble cell adhesion molecules
  • Systemic lupus erythematosus
  • Vascular cell adhesion molecule-1

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