Immunoglobulin G(IgG)is the most abundant plasma glycoprotein and a prominent humoral immune mediator.Glycan composition affects the affinity of IgG to ligands and consequent immune responses.The modification of IgG N...Immunoglobulin G(IgG)is the most abundant plasma glycoprotein and a prominent humoral immune mediator.Glycan composition affects the affinity of IgG to ligands and consequent immune responses.The modification of IgG N-glycosylation is considered to be one of the various mechanisms by which sex hormones modulate the immune system.Although the menstrual cycle is the central sex hormonerelated physiological process in most women of reproductive age,IgG N-glycosylation dynamics during the menstrual cycle have not yet been investigated.To fill this gap,we profiled the plasma IgG Nglycans of 70 healthy premenopausal women at 12 time points during their menstrual cycles(every 7 days for 3 months)using hydrophilic interaction ultra-performance liquid chromatography(HILIC-UPLC).We observed cyclic periodic changes in the N-glycosylation of IgG in association with the menstrual cycle phase and sex hormone concentration in plasma.On the integrated cohort level,the modeled average menstrual cycle effect on the abundance of IgG N-glycosylation traits was low for each trait,with the highest being 1.1%for agalactosylated N-glycans.However,intrapersonal changes were relatively high in some cases;for example,the largest difference between the minimum and maximum values during the menstrual cycle was up to 21%for sialylated N-glycans.Across all measurements,the menstrual cycle phase could explain up to 0.72%of the variation in the abundance of a single IgG glycosylation trait of monogalactosylation.In contrast,up to 99%of the variation in the abundance of digalactosylation could be attributed to interpersonal differences in IgG N-glycosylation.In conclusion,the average extent of changes in the IgG N-glycopattern that occur during the menstrual cycle is small;thus,the IgG N-glycoprofiling of women in large sample-size studies can be performed regardless of menstrual cycle phase.展开更多
The essential role of immunoglobulin G(IgG)in immune system regulation and combatting infectious diseases cannot be fully recognized without an understanding of the changes in its N-glycans attached to the asparagine ...The essential role of immunoglobulin G(IgG)in immune system regulation and combatting infectious diseases cannot be fully recognized without an understanding of the changes in its N-glycans attached to the asparagine 297 of the fragment crystallizable(Fc)domain that occur under such circumstances.These glycans impact the antibody stability,half-life,secretion,immunogenicity,and effector functions.Therefore,in this study,we analyzed and compared the total IgG glycome—at the level of individual glycan structures and derived glycosylation traits(sialylation,galactosylation,fucosylation,and bisecting Nacetylglucosamine(GlcNAc))—of 64 patients with influenza,77 patients with coronavirus disease 2019(COVID-19),and 56 healthy controls.Our study revealed a significant decrease in IgG galactosylation,sialylation,and bisecting GlcNAc(where the latter shows the most significant decrease)in deceased COVID19 patients,whereas IgG fucosylation was increased.On the other hand,IgG galactosylation remained stable in influenza patients and COVID-19 survivors.IgG glycosylation in influenza patients was more time-dependent:In the first seven days of the disease,sialylation increased and fucosylation and bisecting GlcNAc decreased;in the next 21 days,sialylation decreased and fucosylation increased(while bisecting GlcNAc remained stable).The similarity of IgG glycosylation changes in COVID-19 survivors and influenza patients may be the consequence of an adequate immune response to enveloped viruses,while the observed changes in deceased COVID-19 patients may indicate its deviation.展开更多
基金funded by the European Structural and Investment Funds grant for the Croatian National Centre of Research Excellence in Personalized Healthcare(KK.01.1.1.01)Australia-China International Collaborative Grant(NHMRC APP1112767-NSFC 81561128020)+1 种基金National Natural Science Foundation of China(81773527 and 81573215)the European Structural and Investment Funds CEKOM(KK.01.2.2.03.0006).
文摘Immunoglobulin G(IgG)is the most abundant plasma glycoprotein and a prominent humoral immune mediator.Glycan composition affects the affinity of IgG to ligands and consequent immune responses.The modification of IgG N-glycosylation is considered to be one of the various mechanisms by which sex hormones modulate the immune system.Although the menstrual cycle is the central sex hormonerelated physiological process in most women of reproductive age,IgG N-glycosylation dynamics during the menstrual cycle have not yet been investigated.To fill this gap,we profiled the plasma IgG Nglycans of 70 healthy premenopausal women at 12 time points during their menstrual cycles(every 7 days for 3 months)using hydrophilic interaction ultra-performance liquid chromatography(HILIC-UPLC).We observed cyclic periodic changes in the N-glycosylation of IgG in association with the menstrual cycle phase and sex hormone concentration in plasma.On the integrated cohort level,the modeled average menstrual cycle effect on the abundance of IgG N-glycosylation traits was low for each trait,with the highest being 1.1%for agalactosylated N-glycans.However,intrapersonal changes were relatively high in some cases;for example,the largest difference between the minimum and maximum values during the menstrual cycle was up to 21%for sialylated N-glycans.Across all measurements,the menstrual cycle phase could explain up to 0.72%of the variation in the abundance of a single IgG glycosylation trait of monogalactosylation.In contrast,up to 99%of the variation in the abundance of digalactosylation could be attributed to interpersonal differences in IgG N-glycosylation.In conclusion,the average extent of changes in the IgG N-glycopattern that occur during the menstrual cycle is small;thus,the IgG N-glycoprofiling of women in large sample-size studies can be performed regardless of menstrual cycle phase.
基金supported by the European Structural and Investment Funds grant for the Croatian National Centre of Competence in Molecular Diagnostics (KK.01.2.2.03.0006)the Croatian National Centre of Research Excellence in Personalized Healthcare grant (KK.01.1.1.01.0010)supported by the Human Glycome Project。
文摘The essential role of immunoglobulin G(IgG)in immune system regulation and combatting infectious diseases cannot be fully recognized without an understanding of the changes in its N-glycans attached to the asparagine 297 of the fragment crystallizable(Fc)domain that occur under such circumstances.These glycans impact the antibody stability,half-life,secretion,immunogenicity,and effector functions.Therefore,in this study,we analyzed and compared the total IgG glycome—at the level of individual glycan structures and derived glycosylation traits(sialylation,galactosylation,fucosylation,and bisecting Nacetylglucosamine(GlcNAc))—of 64 patients with influenza,77 patients with coronavirus disease 2019(COVID-19),and 56 healthy controls.Our study revealed a significant decrease in IgG galactosylation,sialylation,and bisecting GlcNAc(where the latter shows the most significant decrease)in deceased COVID19 patients,whereas IgG fucosylation was increased.On the other hand,IgG galactosylation remained stable in influenza patients and COVID-19 survivors.IgG glycosylation in influenza patients was more time-dependent:In the first seven days of the disease,sialylation increased and fucosylation and bisecting GlcNAc decreased;in the next 21 days,sialylation decreased and fucosylation increased(while bisecting GlcNAc remained stable).The similarity of IgG glycosylation changes in COVID-19 survivors and influenza patients may be the consequence of an adequate immune response to enveloped viruses,while the observed changes in deceased COVID-19 patients may indicate its deviation.
