IgG Fc Glycosylation Patterns of Preterm Infants Differ With Gestational Age

TY - JOUR

T1 - IgG Fc Glycosylation Patterns of Preterm Infants Differ With Gestational Age

AU - Twisselmann, Nele

AU - Bartsch, Yannic C

AU - Pagel, Julia

AU - Wieg, Christian

AU - Hartz, Annika

AU - Ehlers, Marc

AU - Härtel, Christoph

PY - 2018

Y1 - 2018

N2 - Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections. The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies. This reduction or, even more, a qualitative shift in the type of IgG Fc glycosylation might contribute to the increased risk for sustained inflammatory diseases in preterm infants. It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants. In plasma samples of preterm infants (n = 38), we investigated IgG concentrations by use of ELISA. Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography. Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants. Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD). However, mothers of preterm infants born during second or third trimester of pregnancy did not show significant differences in IgG Fc glycosylation patterns. Thus, the IgG Fc glycosylation patterns of preterm infants depend on their gestational age. Although lack of bisecting N-acetylglucosamine has been associated with less inflammatory effector functions, the decreased IgG Fc galactosylation and sialylation with lower gestational age suggest a rather pro-inflammatory pattern. The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.

AB - Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections. The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies. This reduction or, even more, a qualitative shift in the type of IgG Fc glycosylation might contribute to the increased risk for sustained inflammatory diseases in preterm infants. It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants. In plasma samples of preterm infants (n = 38), we investigated IgG concentrations by use of ELISA. Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography. Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants. Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD). However, mothers of preterm infants born during second or third trimester of pregnancy did not show significant differences in IgG Fc glycosylation patterns. Thus, the IgG Fc glycosylation patterns of preterm infants depend on their gestational age. Although lack of bisecting N-acetylglucosamine has been associated with less inflammatory effector functions, the decreased IgG Fc galactosylation and sialylation with lower gestational age suggest a rather pro-inflammatory pattern. The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.

KW - Biomarkers

KW - Chromatography, Liquid

KW - Enzyme-Linked Immunosorbent Assay

KW - Female

KW - Gestational Age

KW - Humans

KW - Immunoglobulin Fc Fragments/blood

KW - Immunoglobulin G/blood

KW - Infant, Newborn

KW - Infant, Premature/blood

KW - Male

KW - Polysaccharides/blood

KW - Pregnancy

U2 - 10.3389/fimmu.2018.03166

DO - 10.3389/fimmu.2018.03166

M3 - SCORING: Journal article

C2 - 30713537

VL - 9

SP - 3166

JO - FRONT IMMUNOL

JF - FRONT IMMUNOL

SN - 1664-3224

ER -