Evidence of Impact of Maternal HIV Infection on Immunoglobulin Levels in HIV-Exposed Uninfected Children

Abstract

HIV infection affects B cell function and is associated with increased immunoglobulin levels, including in HIV-infected pregnant women. It is unknown if maternal HIV infection affects immunoglobulins in their uninfected children. We investigated this using prospective longitudinal data from children born to HIV-infected women enrolled in the European Collaborative Study (ECS). Data from children enrolled in the European Paediatric Hepatitis C Virus Network (EPHN) were used as a comparison group. Associations between infant and maternal factors and child log(10) total IgG, IgM, and IgA levels were quantified in linear regression analyses. A total of 1751 HIV-uninfected (ECS) and 167 HCV-uninfected children (EPHN) were included. HIV-uninfected children had significantly higher IgG, IgM, and IgA levels than HCV-uninfected children up to at least 24 months. Among HIV-exposed uninfected children, IgG levels from birth until 5 years of age were correlated with increased maternal IgG levels. ART exposure in fetal and early neonatal life was associated with lower IgG. These findings indicate alterations in immunoglobulin levels in uninfected children born to HIV-infected women, suggesting that fetal exposure to a chronically activated maternal immune system is associated with an altered humoral response.

Impact of maternal HIV-1 viremia on lymphocyte subsets among HIV-exposed uninfected infants: protective mechanism or immunodeficiency

“…Some studies have shown a more robust antibody response to vaccines among HEU infants as compared to unexposed, uninfected controls [44,45]. When compared to Hepatitis C exposed infants, HEU infants have been shown to have lower levels of transferred maternal antibodies at birth and significantly higher total immunoglobulin levels until 2 years of age [46], and it is thought that reduced maternal antibody interference with vaccines may contribute to a stronger vaccine response. However, others studies have reported decreased neutralizing-antibody titres to the oral poliovirus vaccine [47] and diminished response to the Hepatitis B vaccine among HEU infants [48].…”

Biomarkers and neurodevelopment in perinatally HIV-infected or exposed youth

“…Evidence suggests presence of abnormalities of fetal immune maturation associated with in-utero exposure to HIV which may persist into childhood in a subtle form even in the absence of perinatal HIV transmission, including lower naïve CD4 + cell counts and thymic output in PHEU infants [25]; presence of HIV-specific CD4 + and CD8 + T cells in PHEU children as old as 7 years [26]; increased IgG, IgM, and IgA levels at 24 months of age [27]; and altered cell-mediated or antibody responses to certain vaccines (Bacillus Calmette-Guérin, pertussis, pneumococcus, and tetanus toxoid) [28]. In-utero exposure to maternal infections and immune activation during critical times of development has been associated with increased risk of autism [29], schizophrenia [30], and bipolar disorder [31].…”

Impaired Haemophilus influenzae Type b Transplacental Antibody Transmission and Declining Antibody Avidity through the First Year of Life Represent Potential Vulnerabilities for HIV-Exposed but -Uninfected Infants

“…Mortality in this population is higher than in infants of uninfected mothers, and these children are at increased risk of pneumonia and diarrhea, which may relate in part to altered immune maturation and function in HEU infants compared with those in unexposed infants of HIV-uninfected mothers (7)(8)(9)(10)(11). Such potential immune impairment may also compromise responses to primary vaccination in the first year of life and lead to specific susceptibility to vaccine-preventable illnesses, including Hib (12).…”