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

Abstract

SUMMARYAn 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,¯-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.

A novel hypothesis for atherosclerosis as a cholesterol sulfate deficiency syndrome

“… Bergner et al, 1981 [ 32 ] Cholesterol sulfatase deficiency leads to massive accumulation of Ch-S in RBCs and plasma. Avila et al, 1996 [ 37 ] Chagas infection induces Ch-S autoantibodies. Paka et al, 1999 [ 98 ] ApoE promotes both cholesterol egress from macrophages in the plaque and sulfation of the glycocalyx.…”

Multivalent Compounds for Antigen-Specific B Cell Tolerance and Treatment of Autoimmune Diseases

“…Divalent, tetravalent, octavalent and polyvalent conjugates Another potential clinical application of B cell tolerance is in xenotransplantation. Porcine organs are an attractive source of replacement organs; however, they are rejected when transplanted into humans due to anti-α-Gal antibodies that recognize the trisaccharide Galα1-3Galβ1-4GlcNAc-R (termed the α-Gal or α-galactosyl epitope), found on various glycoproteins and glycolipids on the surface of porcine epithelial cells [97]. Anti-α-Gal antibodies are not (approx.…”

Sulfate-based lipids: Analysis of healthy human fluids and cell extracts

“…SL appear to be ubiquitous to the whole body and dispersed across fluids (Lam et al, 2014;Larsson et al, 1996;Lee et al, 2016;Muskiet et al, 1983;Sion et al, 2001;Yao et al, 2016) and tissues (Cho et al, 2010;Fujimoto et al, 2000;Moyano et al, 2014;Seng et al, 2014;Serizawa et al, 1990). SL are catalysed by a supergene family of enzymes called sulfotransferases (SULTs) with the transfer of a sulfuryl group (SO3-) to an acceptor hydroxyl group resulting in an increase of water solubility and decrease of biological activity and at the cellular level, SL appear to be gathered in lipid-raft domains (Weerachatyanukul et al, 2007) at the surface of cells (Honke, 2018) contributing to membrane´s electronegative surface charge at physiological pH and thus involved in cell-cell communication processes (Farooqui and Horrocks, 1985;Honke, 2018;Strott and Higashi, 2003) in inflammation (Hu et al, 2007), immunity (Avila et al, 1996;Merten et al, 2001) and infection (Suzuki et al, 2003). The identification of SL-rich microenvironments conducted by MS tissue imaging studies in cancerous tissues (Eberlin et al, 2010;Liu et al, 2010;Masterson et al, 2011), and the recently reported role of SULT enzymatic systems in proper lipoproteins clearance (Stanford et al, 2010) and the detoxification of deleterious oxysterols (Fuda et al, 2007) hints for the possible de-regulation of SL in disease.…”