i(3)so3-galactosylceramide and Chagas-Cardiomyopathy

A specific treatment for Chagas' disease has not yet been discovered, even though the condition is endemic in large parts of the Region of the Americas. Earlier studies have addressed the possibility that the sulfatide galactocerebroside in Trypanosoma cruzi behaves as an immunogen involved in the production of the high antisulfatide antibody levels found in patients with chronic infestation with the parasite. This may be an important factor in the pathogenesis of the cardiac symptoms and peripheral neuropathy seen in Chagas' disease, which is the most important cause of myocarditis in Central and South America and the second most important cause of heart failure in several of the countries located in these subregions. The present study was conducted in order to ascertain whether patients with Chagas' disease and other patients not afflicted with the ailment differ insofar as the presence of antibodies against sulfatide is concerned, and it describes antisulfatide antibody levels in 124 hospital patients (74 men and 50 women) between the ages of 15 and 94 who were in the cardiology unit of Vargas Hospital in Caracas from 1 July to 30 June 1995. Antisulfatide antibody titers were determined by means of enzyme-linked immunosorbent assays (ELISA), and the antigen employed was sulfatide cerebroside obtained from bovine brain tissue. Of the 124 patients under study, 39 (31.5%) suffered from Chagas' disease and had antisulfatide antibody levels higher than those detected in patients without Chagas (P = 0.0298) and in 28 seemingly healthy controls (P = 0.0035). Serum levels of antisulfatide antibodies in patients with other forms of heart disease were also compared with those seen in the control group, and significantly higher levels were found in patients with acute ischemic heart disease (P = 0.0049), rheumatic valvular heart disease (P = 0.0075), chronic ischemic heart disease (P = 0.0464) and bradiarrythmias (P = 0.0157), and significantly lower ones in subjects with hypertensive heart disease (P = 0.0367). These antibody levels showed no correlation with clinical or paraclinical variables indicative of the degree of cardiac compromise. Our results support the notion that antibodies against sulfatide may play a role in the pathogenesis of Chagas' cardiomyopathy and other forms of heart disease and should be further studied in an effort to determine their potential role in these processes.

Topics: Animals; Antibodies, Protozoan; Cattle; Chagas Cardiomyopathy; Chronic Disease; Female; Heart Diseases; Humans; Male; Sulfoglycosphingolipids; Trypanosoma cruzi

Earlier work indicated that Trypanosoma cruzi infection in pregnant rats decreased the amount of myocardial damage that developed in their chronically infected offspring. Given the suspected role of autoimmune mechanisms in the generation of chronic myocarditis, we evaluated whether this maternal intervention was likely to affect the synthesis of autoantibodies in infected young. Autoantibodies were investigated against molecules exhibiting cross-reactivity with T. cruzi antigens or not, that is cerebroside sulphate (sulphatide) and actin, respectively. Female '1' rats (75 days old) that had been mated with syngeneic sires were separated into two groups, one challenged with living trypomastigotes at 7, 14 and 21 days following mating, and the other one given physiologic saline at the same intervals. At the time of weaning, offspring were injected with 10(6)/T. cruzi to constitute two infected groups: young born to infected mothers (InMoTc) and young delivered by uninfected mothers (CoMoTc). Serum antibodies were investigated by ELISA at 30 and 60 days post-infection, which represents acute and chronic infection, respectively. T. cruzi infection was associated with the production of anti-sulphatide antibodies, but the phenomenon was significantly less evident in InMoTc young and virtually unnoticeable during their chronic infection. Unlike the anti-sulphatide results, levels of anti-actin antibodies showed no differences between CoMoTc and InMoTc rats when compared during acute or chronic infection. The decreased production of anti-sulphatide autoantibodies of InMoTc offspring may be due to a modification of the immune repertoire of offspring because of the contact with parasite antigens during ontogeny.

Topics: Actins; Animals; Antigens, Protozoan; Autoantibodies; Chagas Cardiomyopathy; Chagas Disease; Female; Male; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Parasitic; Rats; Sulfoglycosphingolipids; Trypanosoma cruzi