Immunoglobulin profiles in healthy --- and in Human Immunodeficiency Virus type 1 seropositive individuals in Dar es Salaam, Tanzania.

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

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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