title: Expression of antibodies directed to Paracoccidioides brasiliensis glycosphingolipids during the course of paracoccidioidomycosis treatment.
abstract: Paracoccidioidomycosis (PCM) is a granulomatous disease caused by the dimorphic fungus Paracoccidioides brasiliensis. The immunoglobulin classes and isotypes of antibodies directed to acidic glycosphingolipids (GSLs) and glucosylceramide of P. brasiliensis were determined by enzyme-linked immunosorbent assay of sera from 31 PCM patients. The reactivities of 38 serum samples were analyzed by considering the stage of treatment: before antifungal treatment (n = 10), during 1 to 4 months of treatment (T1-4; n = 9), during 5 to 12 months of treatment (T5-12; n = 9), and posttreatment (PT; n = 10). Sera from healthy subjects (n = 12) were used as controls. Only the GSL Pb-1 antigen, which presents the carbohydrate structure Galfbeta1-6(Manalpha1-3)Manbeta1, was reactive with the PCM patient sera. The PCM patient sera did not react with Pb-2, which lacks the Galf residue and which is considered the biosynthetic precursor of Pb-1, indicating that the Galf residue is essential for antibody reactivity. The Pb-1 glycolipid from nontreated patients elicited a primary immune response with immunoglobulin M (IgM) production and subsequent switching to IgG1 production. The IgG1 titer increased after the start of antifungal treatment (T1-4 group), and general decreases in the anti-Pb-1 antibody titers were observed after 5 months of treatment (T5-12 and PT groups). The Pb-1 antigen, an acidic GSL with terminal Galf residue, has potential application as an elicitor of the host immune response in patients with PCM.
authors.affiliation: Department of Biochemistry, Universidade Federal de São Paulo/Escola Paulista de Medicina, Rua Botucatu, 862, São Paulo, SP 04023-900, Brazil.
authors.forename: Silvio
authors.initials: S
authors.lastname: Bertini
authors.forename: Arnaldo L
authors.initials: AL
authors.lastname: Colombo
authors.forename: Helio K
authors.initials: HK
authors.lastname: Takahashi
authors.forename: Anita H
authors.initials: AH
authors.lastname: Straus
mesh_terms: D000328:Adult; D000368:Aged; D000908:Antibodies, Fungal / Q000096:biosynthesis* / Q000097:blood; D006028:Glycosphingolipids / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D010228:Paracoccidioides / Q000276:immunology*; D010229:Paracoccidioidomycosis / Q000276:immunology* / Q000628:therapy
chemical_list: D000908:Antibodies, Fungal; D006028:Glycosphingolipids