Mx. Zhang et al., MANNAN-SPECIFIC IMMUNOGLOBULIN-G ANTIBODIES IN NORMAL HUMAN SERUM MEDIATE CLASSICAL PATHWAY INITIATION OF C3 BINDING TO CANDIDA-ALBICANS, Infection and immunity, 65(9), 1997, pp. 3822-3827
Candida albicans activates both the classical and alternative compleme
nt pathways, Previous studies found that immunoglobulin G (IgG) in nor
mal human serum (NHS) mediates classical pathway initiation, The goal
of this study was to determine the role of candidal mannan-specific hu
man IgG antibodies in complement activation, Mannan was purified from
the yeast cells, and naturally occurring antimannan IgG was isolated f
rom pooled NHS or plasma samples by immunoaffinity chromatography. Ear
ly activation and binding of C3, characteristics of classical pathway
activity, were abolished in yeast-or mannan-absorbed serum but could b
e restored to absorbed serum with added purified antimannan IgG in a d
ose-dependent manner, Microscopically, the immunofluorescence pattern
of initial C3 binding was diffuse over the entire cell surface for yea
st cells incubated in NHS or in mannan-absorbed NHS supplemented with
antimannan IgG but was asynchronous and focal for yeast cells incubate
d in EGTA-treated or mannan-absorbed NHS, The antimannan Ige level in
serum samples from 21 donors varied from 17 to 570 mu g/ml of serum co
mpared to 220 mu g in pooled NHS samples, The rate of initial C3 bindi
ng to yeast cells correlated with the level of antimannan Ige in sera
from different individuals (r(2) = 0.94) and could be accelerated in s
era containing lower amounts of antimannan IgG with exogenous antimann
an IgG. These observations identify antimannan Ige as the initiator of
classical pathway C3 deposition on C. albicans, Given the variability
in the levels of antimannan antibodies in sera from different individ
uals, the presence or absence of these antibodies may be an important
determinant of host resistance to disseminated candidiasis.