Differential antibody isotype expression to the major Paracoccidioides brasiliensis antigen in juvenile and adult form paracoccidioidomycosis

We investigated the relationship between antibody response to the major Par acoccidioides brasiliensis antigen, a 43-kDa glycoprotein, and the two para coccidioidomycosis (PCM) clinical presentations, the juvenile and the adult forms. Total immunoglobulin G (IgG), IgG isotypes, and IgA anti-gp43 antib odies were determined by enzyme-linked immunosorbent assay in patients' ser a. Juvenile PCM patients had higher (P =.003) IgG anti-gp43 levels than adu lt form patients. IgG1 subclass levels, however, were comparable between th e two clinical forms. Patients with the juvenile form had higher (P <.001) IgG4, but lower(P =.03) IgG2 levels than patients with the adult form. The IgG4 isotype, regulated by interleukin 4, was found in all juvenile form pa tients but in only 12% of the adult form patients. In contrast, high levels of the IgG2 isotype, regulated by interferon-gamma, were found in 41% of t he adult PCM patients, mainly those with a more benign disease, but in only 12% of the juvenile patients. IgG3 was either absent or detected at low le vels. These results demonstrate, for the first time, specific IgG4 antibodi es in the humoral immune response of patients with an endemic deep mycosis and suggest that the switch to the IgG subclasses in PCM is regulated by th e patients' T-helper subset (Th-l or Th-2) dominant cytokine profile. A pos sible role for IgG4 in the immunopathogenesis of the juvenile, more severe form of the disease is discussed. Finally, IgA was found mainly in adult fo rm patients, probably as a result of the chronic mucosal antigenic stimulat ion characteristic of this form. (C) Elsevier, Paris.