Immunoglobulin G passive transfer from mothers to infants: total IgG, IgG subclasses and specific antipneumococcal IgG in 6-week Malawian infants exposed or unexposed to HIV

Background: The impaired transplacental passage of IgG from mothers living with HIV to their infants could be one of the causes of the high vulnerability to infections of HIV-exposed uninfected (HEU) infants, but controversial results have been obtained in different settings. The aim of this study was to assess in 6-week old HEU and HIV-unexposed, uninfected (HUU) Malawian infants the total IgG levels, the subclasses profile and the concentrations of global anti-pneumococcal capsular polysaccharide (anti-PCP) IgG and IgG2. Methods: Dried blood spots were collected from 80 infants (40 HEU, 40 HUU) and antibodies concentrations determined by nephelometric method (total IgG and subclasses), or using ELISA (anti-PCP total IgG and IgG2). Results are expressed as median levels with IQR, while the proportions of each subclass out of the total IgG are used to describe the subclasses profile. Results: At 6 weeks HEU infants had higher median levels of total IgG and IgG1 and a significantly lower level of IgG2 [0.376 (0.344–0.523) g/l vs 0.485 (0.374–0.781) g/l, p = 0.037] compared to the HUU counterparts. The IgG subclasses distribution confirmed the underrepresentation of IgG2 (IgG2 represented 5.82% of total IgG in HEU and 8.87% in HUU). The anti-PCP IgG and IgG2 levels were significantly lower in HEU infants [8.9 (5.4–15.1) mg/l vs 16.2 (9.61–25.8) mg/l in HUU, p < 0.001, and 2.69 (1.90–4.29) mg/l vs 4.47 (2.96–5.71) mg/l in HUU, p = 0.001, respectively]. Conclusion: Compared to HUU infants, HEU infants have IgG abnormalities mainly represented by low IgG2 levels, suggesting that despite maternal antiretroviral therapy, the mechanisms of IgG transplacental passage continue to be impaired in women living with HIV. HEU infants also showed a significantly lower level of specific anti-PCP IgG, possibly favouring a high vulnerability to S. pneumoniae infection at an age when protection is mostly depending on maternal IgG.