Abstract
BackgroundTo determine whether optimal use of serial measurements of serum levels of soluble cell adhesion molecules (CAM) can improve monitoring of disease activity in SLE.MethodsSerum 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.ResultsBy 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.ConclusionSubtracting 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0896-7) contains supplementary material, which is available to authorized users.
Highlights
To determine whether optimal use of serial measurements of serum levels of soluble cell adhesion molecules (CAM) can improve monitoring of disease activity in systemic lupus erythematosus (SLE)
Soluble Vascular cell adhesion molecule-1 (VCAM-1) is the most abundant of the circulating CAM, and shows the greatest variation in serum level across a number of inflammatory diseases, with the highest levels observed in active systemic lupus erythematosus (SLE), renal allograft and septic shock [3, 4]. sVCAM-1 levels are elevated in several autoimmune rheumatic diseases including SLE and rheumatoid arthritis (RA) compared with healthy controls, but results for other CAM are conflicting [5,6,7,8,9]. sVCAM-1 levels have been shown to correlate with SLE disease activity in several studies [7,8,9,10], and generally appear to correlate better with disease activity than Soluble intercellular adhesion molecule-1 (sICAM-1) or soluble E-selectin
We observed that the trend in changing levels of sVCAM-1 is a stronger marker of clinical response as measured by reduction in European Consensus Lupus Activity Measure (ECLAM) score, compared with conventional serum markers of SLE disease activity, as well as other soluble CAM
Summary
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. Vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) are IGSF group members which are induced on endothelial cells in response to numerous inflammatory cytokines, including tumour necrosis factor (TNF) and interleukin (IL)-1, and bind integrin partners on leukocytes. Soluble versions of VCAM-1, ICAM-1, E-selectin and P-selectin are shed from endothelial cell surfaces and are readily detectable in serum [2]. Soluble VCAM-1 (sVCAM-1) is the most abundant of the circulating CAM, and shows the greatest variation in serum level across a number of inflammatory diseases, with the highest levels observed in active systemic lupus erythematosus (SLE), renal allograft and septic shock [3, 4]. High levels of sVCAM-1 have been associated with severity of thrombosis in patients with antiphospholipid syndrome [14]
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