Low IgG3 and high IgG4 subclass levels in children with advanced human immunodeficiency virus-type 1 infection and elevated IgE levels.

BACKGROUND

IgG3 and IgG4 levels are not always changed in children perinatally infected with human immunodeficiency virus-type 1 (HIV-1). Elevated IgE levels hallmark the TH1 to TH2 switch occurring in advanced infection and such an unbalanced cytokine network may affect the IgG subclass production.

OBJECTIVE

To examine the different behaviour of IgG3 and IgG4 in the light of elevated IgE levels.

METHODS

IgE and IgG subclass levels were cross-sectionally determined (by radioimmunoassay and enzyme-linked immunosorbent assay, respectively) in 54 HIV-1 perinatally infected children. IgE levels beyond the upper 95% confidence limits (95%CL) of the age-related reference values defined elevated IgE levels. Since immunoglobulin levels physiologically vary with age, individual z-scores of isotype levels were calculated using the upper 95%CL of age-related reference values.

RESULTS

Fifteen (27.7%) children had elevated IgE levels. They had lower IgG3 (mean +/- standard deviation: -1.4+/-0.9 versus 6.9+/-0.9; P < .0001) and higher IgG4 (3.1+/-0.6 versus 0.2+/-0.3; P < .0001) z-scores compared with children without elevated IgE levels. Similar IgG1 (11.7+/-1.8 versus 12.6+/-1.3) and IgG2 (-0.22+/-0.8 versus -0.19+/-0.6) z-scores were found. In children with elevated IgE levels, IgE and IgG3 z-scores inversely correlated (r = -0.867; P < .0001), IgE and IgG4 z-scores directly correlated (r = 0.831; P < .0001) and IgG3 and IgG4 z-scores inversely correlated (r = -0.745; P < .001).

CONCLUSION

Low IgG3 and high IgG4 levels may be present in HIV-1 advanced disease with elevated IgE levels. Changes may be in line with the TH1 to TH2 switch and contribute to disease progression.