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Disease-specific IgG Fc N-glycosylation as personalized biomarkers to differentiate gastric cancer from benign gastric diseases.

ABSTRACT: Interest in the pathophysiological role of IgG fragment crystallizable (Fc) N-linked glycosylation arose from changes in humoral immune responses. In this study, circulating disease-specific IgG (DSIgG) derived from serum immunoinflammation-related protein complexes was isolated from 846 serum samples of 443 patients with benign gastric diseases (BGDs) and 403 patients with gastric cancer (GC), and DSIgG glycopeptides attached to IgG Fc region at the site of Asn297 were analyzed using matrix-assisted laser desorption/ionization- Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS). A total of 22 glycopeptides were detected. Statistical analysis indicated that DSIgG1 G1S, DSIgG2 G0F, G1, G2F, and G2FS as well as DSIgG2 galactosylation and sialylation are significantly associated with sex in BGD patients and that the age-specific glycoforms and glycosylation features from DSIgG between BGD patients and GC patients have similar change trends. In addition, significant changes in galactosylation, sialylation, and bisecting N-acetylglucosamine (GlcNAc) from DSIgG were also observed between two pathophysiological states. Receiver operating characteristic (ROC) analysis indicated that the G2FN/G1FN (from DSIgG2) ratio has an excellent capability to distinguish female BGD patients from female GC patients over the age range of 20-79 years, with the sensitivity of 82.6%, the specificity of 82.6%, and the area under curve (AUC) of 0.872.

SUBMITTER: Zhang D

PROVIDER: S-EPMC4865947 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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.

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Disease-specific IgG Fc N-glycosylation as personalized biomarkers to differentiate gastric cancer from benign gastric diseases.

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