Biomedical subjects

S A Laucella

Publications and source records attributed to S A Laucella.

5 recordsLinked to original sources

PubMed1999

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.

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.

Chagas Disease↗

PubMed1999

Soluble intercellular adhesion molecule-1 in paediatric connective tissue diseases.

The intercellular adhesion molecule-1 (ICAM-1) is a cytokine-induced glycoprotein involved in the recruitment of cells into tissues undergoing inflammatory responses. The aim of this study was to compare the levels of soluble ICAM-1 (s-ICAM-1) in children with juvenile chronic arthritis (JCA) and systemic lupus erythematosus (SLE) and to evaluate the usefulness of this molecule as marker of disease activity. Levels of s-ICAM-1 were measured in sera using a monoclonal antibody sandwich enzyme-linked immunoassay. Serum levels (mean+/-SD) of s-ICAM-1 in 37 children with JCA, 18 patients suffering from SLE and 25 healthy controls were 609+/-184, 513+/-139 and 210+/-95 ng/ml, respectively. A significant difference could be demonstrated between the levels of s-ICAM-1 in sera from each disease, as a group, and those of healthy controls. Higher levels of s-ICAM-1 were recorded in JCA patients with systemic features and patients who had polyarthritis than in children who were pauciarticular. A positive correlation was observed between s-ICAM-1 levels and disease activity score in SLE patients. Moreover, s-ICAM-1 levels closely followed clinical conditions in five children with SLE during follow-up. The data show that s-ICAM-1 levels are increased in children suffering from connective tissue diseases and reflect disease status or activity, suggesting the usefulness of this molecule in the follow-up of these diseases.

Adolescent↗

PubMed1996

Epitopes common to Trypanosoma cruzi and mammalian tissues are recognized by sera from Chagas' disease patients: prognosis value in Chagas disease.

Monoclonal antibodies (MoAbs) raised against Trypanosoma cruzi microsomal fraction (Mc) and cross-reactive with mammalian tissues were used to evaluate the ability of cross-reactive T. cruzi antigens to induce an immune response in Chagas' disease. Thus, we studied the ability of sera from Chagas' disease patients (CDP) with different degrees of cardiac dysfunction to block the immune recognition of these MoAb to the target antigen determining for each serum an inhibition index (II). By means of this approach we inferred that blocking of monoclonal antibody binding to T. cruzi microsomes by subjects' serum represents antibodies with the same reactivity. After serological and medical examinations, individuals were separated into the following groups: Chagas' disease patients without manifest cardiac involvement (CDP-0), CDP with suspected or borderline cardiac disease (CDP-1), CDP with moderate myocardial dysfunction (CDP-2), CDP with overt cardiac dysfunction (CDP-3) and controls including healthy subjects (HS) and patients with idiopathic myocarditis (IMP). The reactivity between MoAb 5F2 and its target antigen was significantly (p < 0.05) inhibited by sera from CDP irrespective of the clinical stage [CDP: n = 46, 50 +/- 20, mean II +/- SD: control: n = 16, 18 +/- 8]. Moreover, 5F2 was able to distinguish (p < 0.05) sera from CDP with mild disease (CDP clinical grade 0/1: n = 26, 34 +/- 18) from that of CDP with severe disease (CDP clinical grade 2/3: n = 20, 67 +/- 7). Moreover, the inhibitory capacity of sera from asymptomatic CDP (CDP-0) correlated with patients age (r = 0.66, p < 0.05). CDP-0 below or equal 40 years of age had results (n = 15, 25 +/- 13) comparable (p > 0.05) to that of controls while mean inhibition of CDP-0 over 40 years of age (n = 5, 60 +/- 5) was indistinguishable (p > 0.05) from that of patients with severe disease. Competitive assay with MoAb 5A9B11 also showed significant differences (p < 0.05) between sera from CDP (n = 46, 46 +/- 24) and controls (n = 13, 5 +/- 5). On the contrary, the differences observed between CDP with different cardiac involvement was not significant (mild: n = 26, 31 +/- 22; severe: n = 20, 66 +/- 11). However a thorough study of data from asymptomatic sera revealed the existence of two levels of reactivity, with low and high capacity to inhibit the reaction of 5A9B11 against Mc. On the contrary, CDP sera showed a blocking activity for 1A10C11 comparable to that of controls (CDP: n = 25, 19 +/- 9; control: n = 12, 14 +/- 6). Some cross-reactive MoAbs recognized epitopes partially composed of carbohydrates. Interestingly, 5F2 and 5A9B11 epitopes did not appear to have carbohydrates moieties. In summary, immunoinhibition assays revealed differences in the immune response of chronic chagasic patients against parasite epitopes. These results have opened the possibility to identify a prognosis marker of the disease suggesting the clinical utility of monitoring levels of these anti-Mc antibodies in patients with chronic Chagas' disease.

Adolescent↗

PubMed1996

Trypanosoma cruzi and mammalian heart cross-reactive antigens.

Monoclonal antibodies produced against T. cruzi microsomal fraction (Mc) were used to investigate the presence of molecular mimicry between the parasite and mammalian tissues. A total of 42 cell lines secreting anti-Mc antibodies were characterized and selected by ELISA, dot blotting and Western blotting assays. Twenty seven supernatants reactive with Mc and/or parasite cytosol (CS) also reacted with human myocardial and/or skeletal muscle antigens by dot blotting assay. Twelve among those cross-reactive hybridomes, which happen to be all of the IgM isotype and to recognize structures on the surface and/or flagellum of the parasite, were selected for cell cloning. Western blotting analysis of these 12 monoclonal antibodies revealed that they mainly recognized bands of 65, 45, 34 and 27 kDa on myocardium and bands of 71, 59, 44 and 30-27 kDa on skeletal muscle. Moreover, seven among them, when assayed by immuno-histochemistry on human and hamster myocardium and skeletal muscle, recognized cytoplasmic antigens, although the monoclonal antibodies 5F2 and 5A9B11 did also bind to the vessel muscle layer. Competitive assays proved the specificity of tissue structures recognition by these monoclonal antibodies. Moreover, this reactivity resulted to be organ specific as they failed to react on lung, stomach and kidney samples. These results demonstrate the cross-reactivity of mammalian and parasite antigens, thus supporting the possibility that molecular mimicry plays a central role in the development of chagasic cardiomyopathy.

Animals↗

PubMedDate not supplied

[Role of cytokines in resistance and pathology in Trypanosoma cruzi infection].

Chagas disease is associated with several immunological alterations. Although resistance against infection with Trypanosoma cruzi has been shown to be influenced by the immune system, its participation in the development of the disease remains unclear. In this regard, cytokines play a fundamental role since they are involved in the regulation of hemopoiesis, lymphopoiesis and affect the function of all cell types involved in an immune response. Interferon gamma (IFN-gamma) has been extensively involved as a protective lymphokine against T. cruzi. Macrophages activated by IFN-gamma result in the release of reactive oxygen metabolites (ROS) and nitric oxide (NO). On the other hand, interleukin 4 (IL-4), interleukin 10 (IL-10) and transforming growth factor beta (TGF-beta) are able to down-regulate the intracellular control of T. cruzi infection by IFN-gamma-activated macrophages, to inhibit NO release and to down-regulate the activity of the TH1 subset of cells (IFN-gamma producers). While TNF-alpha has been implicated in the resistance as well as in the generation of tissue damage, interleukin 6 (IL-6) and interleukin 1 (IL-1) are associated with a variety of alterations in endothelial cell function which may be responsible for the microvascular spasm seen in chagasic myocardiopathy. Several cytokines, including IFN-gamma, IL-1 alpha, IL-6 and TNF-alpha have been shown to modulate the expression of adhesion molecules which participate in inflammatory process by recruitment of lymphocytes into inflammatory sites, contributing to the progression of the local inflammatory reaction in chagasic cardiomyopathy. Thus, it has been shown that acute infection with different strains of T. cruzi induced enhanced expression of ICAM-1 not only on infiltrating leukocytes but also on sarcolemma of cardiocytes and paralleled the production of proinflammatory cytokines. Experimental infection with T. cruzi induces cytokine production which in time modulates the resistance against the parasite and probably the development of chronic Chagas disease. Therefore, it can be postulated that an alteration in quantity and/or quality of cytokine production may be the cause of chronic Chagas disease.

Animals↗