Cholesterol sulphate-reactive autoantibodies are specifically increased in chronic chagasic human patients

Abstract

SUMMARY An antibody reactive with cholesterol sulphate (CS) was characterized in human sera by ELISA, erythrocyte and liposome absorption. This antibody was found evenly distributed between the IgA and IgM classes, and whilst this was present at low titres in the serum of 16% of healthy individuals studied, it was significantly elevated in 78% of Trypanosoma cruzi-infected subjects. No association was found between antibody levels and the degree of myocardial damage. No significant difference in immunoreactivity was found between healthy and chagasic subjects using dehydroepiandrosterone sulphate and pregnenolone sulphate and cholesterol, ergosterol, lanosterol, stigmastanol, β-stigmasterol, pregnenolone, prednisolone and dehydroepiandrosterone as antigens, suggesting that in chagasic sera the whole sterol molecule is important for optimal antibody binding. CS-reactive antibodies were easily purified by absorption either with CS-bearing liposomes or with dextran sulphate gel and further elution with 1.5 m NaCl. The optimal pH of CS–antibody interaction was 4.0 with 85% binding at pH 7.0. Polylysine strongly decreased the binding of these antibodies to the corresponding antigen. Furthermore, these antibodies were strongly absorbed by rabbit and guinea pig erythrocyte but not by rat or human erythrocyte. In contrast with anti-sulphatide antibodies, no significant increase in CS-reactive antibodies was found in dilated cardiomyopathies. Whilst CS itself was not detected in T. cruzi lipid extracts, there is an unidentified sulphated sterol, which migrates close to standard CS and which strongly binds chagasic but not control sera. This latter sterol might be acting in chagasic patients as a powerful antigen, triggering specific autoantibody production.