Associations between the serum levels of PFOS/PFOA and IgG N-glycosylation in adult or children
By Junling Liu, Si Liu, Zhiwen Huang, Yang Fu, Jian Fei, Xin Liu, Zhenyu He
August 25, 2020
Background: Perfluorooctanoic acid (PFOA) and perfluorooctanoic sulfonate (PFOS) have been shown to be associated with disease development. Immunoglobulin G (IgG) N-glycosylation plays a vital role in human immune system and inflammatory activities. Altered IgG glycosylation was one of the molecular markers of various disorders. However, whether the chemicals affect IgG glycosylation has not been investigated.
Methods: Serum samples of 190 individuals including 95 adults and 95 children were selected based on the sex, age and PFOA/PFOS concentration. IgG N-glycome profile was obtained from glycan release, derivatization, and MALDI-MS analysis. One-factor ANOVA test was performed to analyze the association between different levels of PFOS/PFOA and IgG glycosylation changes. Evaluation of the diagnostic performance of significantly changed IgG glycosylation was performed by receiver operating characteristic curve. PFOS/PFOA concentrations were studied in relation to IgG glycosylation by 3D-nonlinear regression analysis.
Results: 10 of the 28 individual IgG glycans were significantly altered between different levels of PFOS/PFOA in adult serum. Among children with high serum levels of PFOS or PFOA, a total of 12 IgG N-glycans were markedly different from those with lower serum PFOS/PFOA. The glycan derived traits for adults with higher serum PFOS or PFOA were marked by significant alterations in IgG digalactosylation, agalactosylation, fucosylation, fucosylated sialylation, and disialylation. Similarly, pronounced changes in agalactosylation, digalactosylation, mono-sialylation and total sialylation, as well as neutral and sialo bisection, were associated with elevated serum PFOS or PFOA in children. Several glycans gained moderately accurate scores of area under the curve for diagnosis of PFOS or PFOA pollution. Nonlinear surface fitting showed the independent or coordinate effect of PFOS or PFOA on the expression of IgG glycosylation.
Conclusions: High levels of PFOS or PFOA in human serum were strongly associated with altered IgG glycosylation and therefore are a potential risk factor for the development of diseases.