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 I 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.