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.
Highlights
Systemic sclerosis (SSc) is an inflammatory obliterative microvasculopathy disorder of unknown etiology characterized by excessive collagen deposition causing fibrosis predominantly in the dermis and in internal organs
No effective treatments exist for skin damage in systemic sclerosis (SSc) patients
Modulation of circulating Lselectin is a promising target for reducing skin damage in diffuse systemic sclerosis (dSSc) patients
Summary
Systemic sclerosis (SSc) is an inflammatory obliterative microvasculopathy disorder of unknown etiology characterized by excessive collagen deposition causing fibrosis predominantly in the dermis and in internal organs. L-selectin (CD62L) is expressed on leukocytes and Pand E-selectin on the endothelium [2] It has been demonstrated using L-selectin deficient mice that defects in this initial adhesive interaction are responsible for the inability of T cells to home to and be sensitized within peripheral lymph nodes [3]. L-selectin expression on circulating nonspecific effector cells (neutrophils and monocytes) has been suggested to be an important mediator of the primary adhesion of these cells at sites of inflammation [5]. L-selectin expression on neutrophils and monocytes may mediate the primary adhesion of these cells at sites of inflammation by mediating the leukocyteleukocyte interactions that facilitate their recruitment. 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
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