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 Galf␤1-6(Man␣1-3)Man␤1, 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.

Sphingolipids as Targets for Treatment of Fungal Infections

“…In dimorphic fungi, such as Histoplasma capsulatum, Paracoccidioides brasiliensis and Blastomyces dermatiditis, the production of GlcCer is mainly related to the yeast-pathogenic form, leading to the presence of antibodies to GlcCer in patient sera and suggesting its importance for fungal virulence [63,65,66]. In the plant pathogen Penicillium digitatum, knocking out the GlcCer synthase gene impairs its virulence in a citrus fruit infection model [67], suggesting that GlcCer plays an important role in virulence not only of mammal pathogens but also of plant pathogens.…”

Biosynthesis and Immunogenicity of Glucosylceramide in Cryptococcus neoformans and Other Human Pathogens

“…Patients undergoing treatment for paracoccidioidomycosis showed first an IgM response and then IgG1, and some even had IgA and IgE production (8). Only 1 of 6 patients with invasive candidiasis and 2 of 14 patients with aspergillosis were found to have antibodies to glycosylinositolphosphorylceramide antigens (8). Although the role of these antibodies during infection is still under investigation, their presence supports the idea of an immunomodulatory role for GSLs.…”

“…These human antibodies were able to inhibit C. neoformans growth and budding (77). A recent publication showed antibodies to acidic complex GSLs during paracoccidioidomycosis (8). Patients undergoing treatment for paracoccidioidomycosis showed first an IgM response and then IgG1, and some even had IgA and IgE production (8).…”

“…A recent publication showed antibodies to acidic complex GSLs during paracoccidioidomycosis (8). Patients undergoing treatment for paracoccidioidomycosis showed first an IgM response and then IgG1, and some even had IgA and IgE production (8). Only 1 of 6 patients with invasive candidiasis and 2 of 14 patients with aspergillosis were found to have antibodies to glycosylinositolphosphorylceramide antigens (8).…”

Profile of total IgG, IgG1, IgG2, IgG3 and IgG4 levels in sera of patients with paracoccidioidomycosis: treatment follow-up using Mexo and rPb27 as antigens in an ELISA

“…The second part of our study determined the levels of total IgG and its subclasses in chronic PCM patients before, during and after treatment. Some groups have attempted to determine a correlation between antibody levels and disease severity in PCM patients, especially in the follow-up period after treatment (Bueno et al 1997, Martins et al 1997, Reis et al 2005, Anastácio et al 2007, Bertini et al 2007, Yoshida et al 2009), but this association is still controversial. Restrepo et al (1978) found decreased antibody levels after six months of treatment using DI and CF tests in only three of the 16 patients analysed.…”