Soluble platelet selectin (sP-selectin) and soluble vascular cell adhesion molecule-1 (sVCAM-1) decrease during therapy with benznidazole in children with indeterminate form of Chagas' disease

Abstract

The immune response against Trypanosoma cruzi infection has been associated with both protection and pathogenesis. Central events in host defence system- and immune-mediated damage are tightly regulated by cell adhesion molecules (CAM). Levels of sP-selectin and sVCAM-1 were measured in sera from 41 children with the indeterminate phase of Chagas' disease. Simultaneously, levels of soluble adhesion molecule were also quantified in Chagas' disease children undergoing specific chemotherapy with benznidazole. Levels of sP-selectin and sVCAM-1 were found to be elevated in children with indeterminate Chagas' disease before aetiologic therapy was started. However, a small group of patients showed sP-selectin and sVCAM-1 levels comparable to those of non-infected children. A positive correlation between levels of sVCAM-1 and sP-selectin in sera from Chagas' disease patients was found. There was a significantly greater decrease in the titres of sP-selectin and sVCAM-1 in those children receiving benznidazole therapy compared with those children receiving placebo. Measurement of soluble adhesion molecules revealed differences in the activation of the immune system in children with the indeterminate form of Chagas' disease. The early decrease of sP-selectin and sVCAM-1 levels after anti-parasitic treatment suggests that these molecules might be valuable indicators of effective parasitologic clearance.

Fig. 1

Levels of sP-selectin and sVCAM-1 during the indeterminate phase of Chagas' disease. Sera from 41 children with indeterminate Chagas' disease and 15 non-infected controls were tested for sP-selectin (n = 30) and sVCAM-1 (n = 41) by a two-site ELISA assay. Each point represents one patient. The group mean and s.d. of the mean are also depicted. *Serum levels of sP-selectin and sVCAM-1 were significantly different (Mann–Whitney U-test, P < 0.05) between Chagas' disease patients and control group).

Fig. 2

Correlation between serum concentrations of sP-selectin and sVCAM-1 in 27 children suffering from indeterminate Chagas' disease (Spearman's rank correlation coefficient r = 0.61, P < 0.0001) before anti-Trypanozoma cruzi therapy.

Fig. 3

Serum levels of sP-selectin and sVCAM-1 in children with indeterminate phase of Trypanozoma cruzi infection before and after 60 days of benznidazole therapy (open symbols) or placebo (closed symbols). Circles represent Chagas' disease patients with baseline s-CAM levels above the cut-off value, whereas individuals with baseline sCAM levels under the cut-off value are represented by triangles. *P < 0.05, Mann–Whitney U-test on post-treatment–pretreatment differences between benznidazole and placebo treatment groups. Cut-off values: 52 ng/ml for sP-selectin and 406 ng/ml for sVCAM-1.