Deficit of IgG2 in HIV-positive pregnant women is responsible of inadequate IgG2 levels in their HIV-uninfected children in Malawi

Abstract

Background: Transplacental passage of IgGs is impaired in HIV + pregnant women, possibly determining an inadequate immunological protection in their children. We aimed to determine the impact of maternal immunological IgG profile and immunoactivation status on the efficiency of transplacental passage of IgG subclasses in HIV + mothers.

Methods: 16 mother/infants pairs were studied in Malawi. Mothers received antiretroviral therapy (ART) from the third trimester of pregnancy. Determinations of pre-ART levels of maternal sCD14, of IgG subclasses in mothers at delivery and in their 1-month-old infants, were performed using commercial ELISA kits.

Results: At delivery, after a median of 10 weeks of ART, 12/16 mothers were hypergammaglobulinemic, with IgG levels (20.5 mg/ml, 95% CI:18.8-26.8) directly correlated to the plasmatic levels of sCD14 (r = 0.640, p = 0.014). IgG1 levels (17.9 mg/ml) accounted for 82% of IgG, IgG3 and IgG4 levels were in the normal range. A profound deficit of IgG2 was observed both in mothers (0.60 mg/ml) and in infants (0.14 mg/ml). Placental transfer ratio (range 0.16-0.42) did not show a selective impairment between the different IgG subclasses. The transplacental passage of all IgG subclasses was decreased in the presence of maternal IgG over 16 mg/ml (significantly for IgG1, p = 0.031) and of high levels of sCD14 (p = 0.063).

Conclusions: Transplacental passage was reduced for all IgG subclasses and inversely correlated to high levels of maternal IgGs and to the degree of immunoactivation. The profound depression of IgG2 in mothers suggests that IgG2 neonatal levels mostly reflect the maternal deficit rather than a selective impairment of IgG2 transfer.

Keywords: HIV; IgG subclasses; Malawi; Transplacental passage.