Occurrences, immunoglobulin classes, and biological activities of antibodies in normal human serum that are reactive with Cryptococcus neoformans glucuronoxylomannan

Abstract

Serum obtained from normal human subjects contains antibodies reactive in an enzyme-linked immunosorbent assay with the glucuronoxylomannan (GXM) of Cryptococcus neoformans. The frequency of occurrence of class-specific antibodies among normal subjects was 28% for immunoglobulin G (IgG), 98% for IgM, and 3% for IgA. Anti-GXM antibodies with kappa light chains occurred in 98% of normal subjects, while the occurrence of lambda light chains was 28%. Each of five subjects with high levels of anti-GXM IgG antibodies had readily detectable antibodies of the IgG2 isotype; two of the five subjects had readily detectable IgGl antibody. An examination of sera from human immunodeficiency virus-infected patients showed that human immunodeficiency virus infection was accompanied by a significant decrease in the occurrence of IgM antibodies and anti-GXM antibodies with kappa light chains; these decreases occurred early in infection when CD4 counts were still .500 cells per ,ul. A slight but not statistically significant decrease in the occurrence of anti-GXM IgG antibodies was seen only in patients with CD4 levels of <200 cells per ,lI. Sera from normal subjects with high levels of anti-GXM IgG antibodies were examined to identify any contribution of the antibodies to complement activation or to opsonization of the yeast cells. An analysis of the kinetics for activation and binding of C3 to the yeast cell showed no pattern of quantitative or qualitative differences between sera with high or low levels of anti-GXM IgG antibodies. Phagocytosis studies showed that the naturally occurring IgG antibodies did not contribute to opsonization of the yeast cells.

Detection of IgM and IgG antibodies to Cryptococcus neoformans proteins in blood donors and HIV patients with active cryptococcosis

“…Previous study reported that humans have preexisting antibodies reactive with glucuronoxylomannan. [14][15][16][17] Three studies [7][8][9] reported preexisting antibodies in human against cryptococcal proteins. The findings provide indirect evidence of C. neoformans infections in immunocompetent individuals and support the concept that humans may have ongoing exposure to C. neoformans.…”

Capsular polysaccharide induction of apoptosis by intrinsic and extrinsic mechanisms

“…Glucuronoxylomannan was isolated from the culture supernatant fluid of serotype A strain CN 6, as previously described (Houpt et al, 1994;Cherniak et al, 1980). Isolated soluble GXM contained < 125 pg LPS mg -1 of GXM as detected by Limulus amebocyte lysate assay (Sigma).…”

Cryptococcus neoformans capsular polysaccharide component galactoxylomannan induces apoptosis of human T-cells through activation of caspase-8

“…To eliminate LPS contamination in the GalXM preparation, this polysaccharide was dialysed extensively versus LPS-free water and the dialysate changed until negative by Limulus amobocyte assay. GXM was obtained from TR Kozel (Department of Microbiology and Immunology, University of Nevada, Reno, NE) and was isolated and purified as described elsewhere (Cherniak et al, 1980;Houpt et al, 1994). Purified soluble GXM contained < 125 pg LPS/mg of GXM as detected by Limulus amebocytes lysate assay.…”