Markers of endothelial cell activation and immune activation are increased in patients with severe leptospirosis and associated with disease severity.

OBJECTIVES: Previous studies concluded that haemorrhage is one of the most accurate prognostic factors of mortality in leptospirosis. Therefore, endothelial cell activation was investigated in relation to disease severity in severe leptospirosis. METHODS: Prospective cohort study of severe leptospirosis patients. Plasma levels of sE-selectin and Von Willebrand factor (VWF) were determined. Consequently, an in vitro endothelial cell model was used to assess endothelial activation after exposure to virulent Leptospira. Finally, immune activation, as a potential contributing factor to endothelial cell activation, was determined by soluble IL2-receptor (sIL-2r) and soluble Fas-ligand (sFasL) levels. RESULTS: Plasma levels of sE-selectin and VWF strongly increased in patients compared to healthy controls. Furthermore, sE-selectin was significantly elevated (203 ng/ml vs. 157 ng/ml, p < 0.05) in survivors compared to non-survivors. Endothelial cells exposed to virulent Leptospira showed increased VWF expression. E-selectin and ICAM-1 expression did not change. Immunohistochemistry revealed the presence of intracellular Leptospira and qPCR suggested replication. In vivo analysis showed that increased levels of sFasL and sIL-2r were both strongly associated with mortality. Furthermore sIL-2r levels were increased in patients that developed bleeding and significantly correlated to duration of hospital stay. DISCUSSION: Markers of endothelial activation and immune activation were associated with disease severity in leptospirosis patients.

Determination of soluble Fas and soluble Fas ligand in patients with systemic lupus erythematosus / 대한임상병리학회지

BACKGROUND: The Fas/Fas ligand (FasL) system plays an important role in apoptosis by involvement in various immunologic functions, especially the removal of autoreactive and activated T-cells. sFas is a variant of the Fas receptor molecule, which lacks the transmembrane domain by alternative splicing of Fas mRNA and has an inhibitory effect in apoptosis by inhibition of the Fas/FasL pathway. sFasL is a coverted form of FasL by metalloproteinase and is increased in various malignant and autoimmune diseases. In this study, we investigated the expression of sFas and sFasL in systemic lupus erythematosus (SLE) and evaluated their usefulness as markers of disease activity. MATERIALS AND METHODS: The concentration of sFas and sFasL in sera from 43 patients with SLE, 17 with rheumatoid arthritis (RA) and 15 normal healthy persons were measured using sFas (S) ELISA Kit and sFas Ligand ELISA Kit (MBL Co., LTD., Nagoya, Japan), respectively. Twenty of 43 SLE sera were paired samples of 10 patients obtained on admission and discharge. RESULTS: The concentration of sFas in SLE (3.12 +/- 2.28 ng/mL) was significantly higher than in RA (2.23 +/- 0.37 ng/mL) and in the normal control (2.12 +/- 0.33 ng/mL). In particular, the concentration of sFas in sera on admission (4.35 +/- 3.68 ng/mL) was significantly higher than in the sera on discharge (2.89 +/- 0.66 ng/mL), but, the concentration of sFasL among the 3 groups was not statistically different. CONCLUSIONS: These results suggest that apoptosis is involved in the pathogenesis of SLE and sFas might be a useful marker as a predictor of disease activity. Further study on the correlation between sFas and other disease activity markers, such as CRP, CH50, CD4 cell count and autoantibody titer is needed. Also, the evalution of sFas as a predictor of disease progression on follow-up studies of these patients is needed.