L-selectin and Skin Damage in Systemic Sclerosis

Abstract

BackgroundL-selectin ligands are induced on the endothelium of inflammatory sites. L-selectin expression on neutrophils and monocytes may mediate the primary adhesion of these cells at sites of inflammation by mediating the leukocyte-leukocyte interactions that facilitate their recruitment. L-selectin retains functional activity in its soluble form. Levels of soluble L-selectin have been reported as both elevated and lowered in patients with systemic sclerosis (SSc). This preliminary study seeks to discern amongst these disparate results and to discover whether there is an association between L-selectin concentrations in plasma and skin damage in SSc patients.Methodology and Principal FindingsNineteen cases with limited systemic sclerosis (lSSc) and 11 cases with diffuse systemic sclerosis (dSSc) were compared on a pairwise basis to age- and sex-matched controls. Criteria of the American College of Rheumatology were used to diagnose SSc. Skin involvement was assessed using the modified Rodnan skin score (mRSS). We find no association between mRSS and plasma L-selectin concentration in lSSc cases (p = 0.9944) but a statistically significant negative correlation in dSSc cases (R2 = 73.11 per cent, p = 0.0008). The interpretation of the slope for dSSc cases is that for each increase of 100 ng/ml in soluble L-selectin concentration, the mRSS drops 4.22 (95 per cent CI: 2.29, 6.16). There was also a highly statistically significant negative correlation between sL-selectin and disease activity (p = 0.0007) and severity (p = 0.0007) in dSSc cases but not in lSSc cases (p = 0.2596, p = 0.7575, respectively).Conclusions and SignificanceNo effective treatments exist for skin damage in SSc patients. Nor is there a laboratory alternative to the modified Rodnan skin score as is the case for other organs within the body. Modulation of circulating L-selectin is a promising target for reducing skin damage in dSSc patients. Plasma levels of soluble L-selectin could serve as an outcome measure for dSSc patients in clinical trials.

Two new susceptibility loci 1q24.2 and 11p11.2 confer risk to severe acne

“…Another study also reported a highly significant negative correlation between soluble L-selectin and the inflammatory disorder diffuse systemic sclerosis (dSSc) 28 . Similarly, in mice lacking both L-selectin and intercellular adhesion molecular-1 (ICAM-1) expression, the healing of wounds is delayed, probably due to the decreased leukocyte accumulation into the wound site 29 .…”

Serum Adhesion Molecule Levels as Prognostic Markers in Patients with Early Systemic Sclerosis: A Multicentre, Prospective, Observational Study

“…Significantly reduced levels of serum L-selectin have been reported in patients with SSc [52]. In a recent report, serum L-selectin levels were reduced and were negatively associated with skin damage in patients with dcSSc [53]. By contrast, serum levels of L-selectin were significantly elevated in patients with SSc in another study [54].…”

Versican is upregulated in circulating monocytes in patients with systemic sclerosis and amplifies a CCL2-mediated pathogenic loop

“…For example, circulating levels of soluble L -selectin and CXCL8 were increased in SSc patients versus healthy controls [63,64]. In addition, gene expression of CCR1 was shown to be upregulated in PBMCs derived from patients with lcSSc and pulmonary arterial hypertension [65].…”