Abstract:
Serum levels of IgG, IgA, IgM, IgD, IgE, and IgG subclasses were
determined in 60 sera from pregnant mothers and their newborns, 50 sera
from HIV-l serone~ative blood donors and 50 sera from HIV-1
seropositive individuals from Dar es Salaam. The mean levels of
immu~oglobulin isotypes in maternal sera were 19.9g/l, 2.79g/l,
3.08g/l, 68.33IU/ml, and 2689.33IU/ml for IgG, IgA, IgM, IgD, and IgE
respectively. The mean IgG subclass levels in maternal sera were
11.99g/l, 3.74g/l, 2.38g/l, and 1.11g/l for IgG1, IgG2, IgG3, and IgG4
respectively.
of
subclasses
Placental
transfer
all
IgG
was
demonstrated. In the corresponding cord sera, the mean levels for total
IgG and IgG subclasses were 16.82g/l, 12.77g/l, 0.86g/l, 2.11g/l, and
0.68g/l for total IgG, IgG1, IgG2, IgG3, and IgG4 respectively. The
order of magnitude for the fetal/maternal IgG subclass ratios was
IgG1>IgG3>IgG4>IgG2, which resembles the documented order -of binding
affinity of the human IgG subclasses to placental Fc receptors.
The mean serum levels of all immunoglobulin classes except for
IgE were significantly higher (P=0.0001) in HIV-1 seropositive
individuals than in HIV seronegative controls. Mean levels in controls
were 17.97g/l, 2.07g/l, 1.8g/l, 52.26IU/ml, and 2965IU/ml for IgG, IgA,
IgM, IgD, and IgE respectively. All classes, except IgG, showed an
~ncreasing trend with evolution of the disease from asymptomatic phase
o AIDS phase. The mean IgG subclass levels in controls were 12.76g/l,
1. 76g/l,
1.5g/l, and 0.48g/l for IgG1,
IgG2, IgG3,
and IgG4
respectively. The mean levels of IgG1 and IgG3 were significantly
higher in HIV-l seropositive subjects than in HIV-1 seronegative
xiv
controls (p=O.OOOl for IgGl and p<O.OOOl for IgG3). With evolution from
asymptomatic to AIDS phase, mean IgGl and IgG2 levels remained
constant, while mean IgG3 level doubled. IgG4 concentration decreased
with progression to AIDS phase.
Investigation of anti-HIV-l IgG subclass response to gp41 and p24
revealed responses in all four subclasses. In the asymptomatic phase,
response to gp41 was IgGl and IgG4 restricted, while response to p24
was mainly IgGl and IgG3. In the AIDS phase, the IgG subclass response
to HIV-l antigens was IgGl and IgG2 to gp41, and IgGl and IgG4 to p24.
Findings obtained in the present study, support the theory of Fc
receptor-mediated placental transfer of IgG subclasses, and that
perhaps this mechanism is independent of racial and geographical
factors. Polyisotypic hypergammaglobulinemia and serum IgG subclass
dysbalances were demonstrated in HIV-l seropositive subjects from an
area with mainly heterosexual HIV-l transmission pattern. The mode of
HIV-l transmission therefore does not appear to influence these
phenomena. Isotypic response to gp41 and p24 was demonstrated in all
four IgG subclasses. The finding of an IgG3 response to gp41 is of
interest in view of the role of IgG3 subclass in the neutralization of
viral ant
