Date Published: July 7, 2017
Publisher: Public Library of Science
Author(s): Loic Raffray, Claude Giry, Yoga Thirapathi, Anne-Hélène Reboux, Marie-Christine Jaffar-Bandjee, Philippe Gasque, Yung-Fu Chang.
Leptospirosis is a multisystemic zoonotic disease with infiltration of visceral organs by Leptospira. The capacity of the vascular endothelium to grant immune cell recruitment and activation in target organs during the disease course remains poorly characterized. We ascertained the levels of expression of several soluble cell adhesion molecules (CAM) notably expressed by endothelial cells in human leptospirosis. We prospectively enrolled 20 hospitalized patients and compared them to 10 healthy controls. Disease severity was defined by one or more organ failures, or death. Plasmatic concentrations of soluble CAM were assessed by multiplex bead assay at the time of patient presentation (M0) and 1 month after hospital discharge. The levels of soluble E-selectin (sCD62E) and soluble intercellular adhesion molecule 1 (sICAM-1, sCD53) were significantly increased in patients compared to controls (p<0.0001) and at 1 month (p<0.0001) with median values at 978 ng/ml (interquartile ranges 787–1164; sCD62E) and 1021 ng/ml (690–1428; sCD53). At M0, Soluble P-selectin level (sCD62P) was found to be decreased with levels at 60 ng/ml (0–631) versus 711 ng/ml (343–1113) for healthy controls (p<0.05). Levels of sICAM-3 (sCD50), sVCAM-1 (vascular cell adhesion molecule, sCD106) and sPECAM-1 (platelet endothelial cell adhesion molecule, sCD31) were not different from healthy subjects at M0. This study shows that two adhesion molecules, shed as soluble forms, are elevated during the acute phase of leptospirosis: E-selectin and s-ICAM1. These molecules may interfere with the process of immune cell recruitment to clear Leptospira at tissue levels.
Leptospirosis is a zoonotic disease caused by Leptospira species, with a recent estimate of 1 million cases per year . The course of the disease includes a broad spectrum of manifestations, from influenza-like illness to multi-organ failure with icteric hepatitis, deep thrombocytopenia, acute renal failure and more rarely intra-alveolar hemorrhage . The mortality ranges from 5% to 15% especially during lung hemorrhage [1,2]. Despite increasing evidence regarding the pathological mechanisms of the disease, much remains to be demonstrated to have a better understanding of this multisystemic disease, and specially the host-pathogen interactions .
The aim of this study was to assess indirectly the relative contribution of vascular endothelial cells in human leptospirosis by measuring the levels of several soluble CAMs in blood. We analyzed plasma levels of several of the key CAMs shed as soluble forms. These sCAMs have been considered prognostic biomarkers of severity of systemic inflammation but the clinical importance of monitoring such changes remains to be established . We herein report a major increase in sE-selectin and sICAM-1 levels in patients with leptospirosis, whereas sP-selectin levels were lower compared to control healthy subjects. Our results indicate that endothelial cells may be activated during leptospirosis and that yet ill-characterized mechanisms are likely to contribute to the release of soluble forms of the CAMs through the activity of sheddases, membrane-bound proteases or caspases.