CHRONIC MUCOCUTANEOUS CANDIDIASIS .2. CLASS AND SUBCLASS OF SPECIFIC ANTIBODY-RESPONSES IN-VIVO AND IN-VITRO

Patients with chronic mucocutaneous candidiasis (CMC) succumb to persi stent infections with the opportunistic yeast Candida. Impaired cell-m ediated responses to Candida have been repeatedly reported while antib ody responses were mostly found to be normal. The underlying defect re mains poorly understood. It has recently been shown that CMC patients are also susceptible to infections with encapsulated bacteria, and may have associated IgG2 and IgG4 deficiency. Our previous studies demons trated altered cytokine production in CMC patients. As cytokines can i nfluence production and isotype of specific antibody, in 10 patients w ith CMC we measured the levels and isotype distributions of serum anti bodies to Candida antigens (CAg), pneumococcal polysaccharide (PPS) an d tetanus toroid (TT) antigens. Peripheral blood lymphocytes were also stimulated in culture and the antibodies made in vitro were measured. Our data demonstrated that in vivo, CMC patients had very high levels of IgG and IgA CAg-specific antibodies. CAg-specific and PPS-specific IgG1 was markedly higher than in controls. Children but not adults wi th CMC had significantly lower levels of IgG2-specific antibody to CAg and PPS compared with age-matched controls. Patients had significantl y higher levels of IgG3-specific antibody to all three antigens tested . These findings were in accordance with increased total IgG and IgG3 levels seen in CMC patients. In vitro, CMC patients, particularly chil dren, did not respond as frequently to antigen stimulation as did thei r healthy controls. The level of specific antibody produced was also l ower to all antigens tested, as was the amount of total immunoglobulin s following antigenic and particularly mitogenic stimulation. Addition of interferon-alpha (IFN-alpha) or IFN-gamma to cultures had variable , sometimes marked, effects. Our results demonstrate that CMC patients manifest subtle alterations in specific antibody responses to CAg, PP S and TT, which are most pronounced in children. This may relate to al tered cytokine production also seen in these patients.