Levels of certain endothelial biomarkers during the acute phase and convalescence in patients with different severity of Mediterranean spotted fever.

INTRODUCTION: Mediterranean spotted fever (MSF) is a tick-borne disease caused by Rickettsia conorii subspp. conorii. It is transmitted by the bite of the tick Rhipicephalus sanguineus. Modified by the rickettsial invasion, the micro-vascular endothelium acquires an activated inflammatory phenotype and initiates secretion of cytokines and expression of cell adhesion molecules (CAMs) and chemoattractans.

AIM: This study aims at investigating the alterations in the soluble cellular adhesion molecules (sCAMs) and chemokine MCP-1 levels in patients with MSF of varying severity in the acute and convalescence stage in order to assess their diagnostic and prognostic value.

MATERIALS AND METHODS: The soluble forms of cellular adhesion molecules (sCAMs)--sE-selectin and sP-selectin, the intercellular (sICAM-1) and vascular (sVCAM-1) adhesion molecules as well as the monocyte chemoattractant protein-1 (MCP-1) were studied in the sera of 80 patients with MSF. The presence of MSF was confirmed serologically by indirect fluorescence assay (IFA). In order to study disease dynamics, serum samples from 80 patients were drawn on day 1 following the onset of rash; in 60 patients (part of the surveyed 80) a second sample was taken in the convalescence period--14 days post hospital discharge. The investigation was focused on mild, moderate and severe forms of MSF. Enzyme linked immune-sorbent assay was used for sCAMs determination (Quantikine IVD colorimetric

RESULTS: Overall, in the acute stage, patients presented with increased levels of sE-selectin, sICAM-1, sVCAM-1 and MCP-1, whereas sP-selectin level was decreased. The levels of sE-selectin, sICAM-1 and sVCAM-1 were significantly elevated in mild, moderate and severe forms of the disease with sE-selectin level exhibiting a plateau tendency and sICAM and sVCAM levels demonstrating an upward trend from mild towards severe MSF forms. MCP-1 level was elevated only in severe MSF. In all forms of MSF, in the convalescence period, sICAM-1, sVCAM-1 and MCP-1 concentration returned to reference levels whereas sE-selectin level persisted elevated. In the convalescence stage, sP- selectin concentration also showed an upward tendency, which in severe forms of MSF slightly exceeded the level in controls. sP-selectin levels correlated directly with platelet count, whereas sICAM-1 and sVCAM-1 levels showed a reverse correlation, sE-selectin, sICAM-1 and MCP-1 levels directly correlated with aminotransferase activity (ALT and/or AST).

CONCLUSION: The soluble forms of CAMs reflect the endothelial inflammatory potential. There is evidence that endothelium activation is more potent in severe forms of MSF. Assessment of the endothelial response in the course of the disease is an important predictor of the outcome, the choice of therapeutic approach and disease prognosis.