Clinical Mass Spectrometry Discovered Human IgG Sialylation as a Potential Biosignature for Kidney Function

Kao, Chih-Chin; Wang, San-Yuan; Chuang, Yung-Kun; Lee, Wei-Yuan; Chang, Wei‐Chiao; Wu, Mai‐Szu; Kuo, Tai-Chih; Tsai, I‐Lin

doi:10.3390/jpm11080761

Cited by 5 publications

(4 citation statements)

References 27 publications

(28 reference statements)

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“…Studies have identified decreased levels of sialylated glycans in renal disease patients ( 47 ). In another study, a decrease in GP16 and GP18 levels was found in CKD patients ( 48 ), aligning with our research findings. Galactosylation, a precursor of sialylation, frequently shows a similar directional alteration ( 32 ).…”

Section: Discussionsupporting

confidence: 92%

Association between immunoglobulin G N-glycosylation and lupus nephritis in female patients with systemic lupus erythematosus: a case-control study

Lu,

Wang,

Wang

et al. 2023

Front. Immunol.

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BackgroundLupus nephritis (LN) is a crucial complication of systemic lupus erythematosus (SLE) and has important clinical implications in guiding treatment. N-glycosylation of immunoglobulin G (IgG) plays a key role in the development of SLE by affecting the balance of anti-inflammatory and proinflammatory responses. This study aimed to evaluate the performance of IgG N-glycosylation for diagnosing LN in a sample of female SLE patients.MethodsThis case-control study recruited 188 women with SLE, including 94 patients with LN and 94 age-matched patients without LN. The profiles of plasma IgG N-glycans were detected by hydrophilic interaction chromatography with ultra-performance liquid chromatography (HILIC-UPLC). A multivariate logistic regression model was used to explore the associations between IgG N-glycans and LN. A diagnostic model was developed using the significant glycans as well as demographic factors. The performance of IgG N-glycans in the diagnosis of LN was evaluated by receiver operating characteristic (ROC) curve analysis, and the area under the curve (AUC) and its 95% confidence interval (CI) were calculated.ResultsThere were significant differences in 9 initial glycans (GP2, GP4, GP6, GP8, GP10, GP14, GP16, GP18 and GP23) between women with SLE with and without LN (P < 0.05). The levels of sialylated, galactosylated and fucosylated glycans were significantly lower in the LN patients than in the control group, while bisected N-acetylglucosamine (GlcNAc) glycans were increased in LN patients (P < 0.05). GP8, GP10, GP18, and anemia were included in our diagnostic model, which performed well in differentiating female SLE patients with LN from those without LN (AUC = 0.792, 95% CI: 0.727 to 0.858).ConclusionOur findings indicate that decreased sialylation, galactosylation, and core fucosylation and increased bisecting GlcNAc might play a role in the development of LN by upregulating the proinflammatory response of IgG. IgG N-glycans can serve as potential biomarkers to differentiate individuals with LN among SLE patients.

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Section: Discussionsupporting

confidence: 92%

Association between immunoglobulin G N-glycosylation and lupus nephritis in female patients with systemic lupus erythematosus: a case-control study

Lu,

Wang,

Wang

et al. 2023

Front. Immunol.

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“…Barrios and Menni et al demonstrated that 14 different IgG glycan traits belonging to galactosylation, sialylation, and bisecting features were associated with kidney function [21]. Kao et al showed that IgG1 sialylation was associated with eGFR (Estimated Glomerular Filtration Rate) values, confirming that the decrease of sialylated IgG is an indicator of the inflammatory status of individuals with lower kidney function [43].…”

Section: Discussionmentioning

confidence: 98%

Definition of IgG Subclass-Specific Glycopatterns in Idiopathic Membranous Nephropathy: Aberrant IgG Glycoforms in Blood

Chinello

Haan

Capitoli

et al. 2022

IJMS

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The podocyte injury, and consequent proteinuria, that characterize the pathology of idiopathic membranous nephropathy (IMN) is mediated by an autoimmune reaction against podocyte antigens. In particular, the activation of pathways leading to abundant renal deposits of complement is likely to involve the binding of mannose-binding lectin (MBL) to aberrant glycans on immunoglobulins. To obtain a landscape of circulatory IgG Fc glycosylation characterizing this disease, we conducted a systematic N-glycan profiling study of IgG1, 2, and 4 by mass spectrometry. The cohort included 57 IMN patients, a pathological control group with nephrotic syndrome (PN) (n = 20), and 88 healthy control subjects. The effect of sex and age was assessed in all groups and controlled by rigorous matching. Several IgG Fc glycan traits were found to be associated with IMN. Interestingly, among them, only IgG4-related results were specific for IMN and not for PN. Hypo-galactosylation of IgG4, already shown for IMN, was observed to occur in the absence of core fucose, in line with a probable increase of pro-inflammatory IgG. In addition, elevated levels of fucosylated IgG4, along with low levels of hybrid-type glycans, were detected. Some of these IgG4 alterations are likely to be more pronounced in high PLA2R (phospholipase A2 receptor) patients. IgG Fc glycosylation patterns associated with IMN warrant further studies of their role in disease mechanisms and may eventually enrich the diagnostic spectrum regarding patient stratification.

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“…In addition, the changes in glycosylation patterns with a notable increase in fucose exposure correlate with the late stage of sepsis when neutrophil elastase activity is elevated. This made neutrophil-associated enzymatic release a potential target in studies of the etiopathogenesis of sepsis [ 65 , 67 ]. However, the relationship between this correlation has not been fully revealed.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Depletion Changes the N-Glycosylation Pattern of IgG in Experimental Murine Sepsis

Yaykasli,

van Schie,

Toes

et al. 2024

IJMS

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Sepsis is a life-threatening condition with a rising disease burden worldwide. It is a multifactorial disease and is defined as a dysregulated host response to infection. Neutrophils have been shown to be involved in the pathogenesis of sepsis by exacerbating inflammation. However, the exact effector mechanism of action still remains a mystery. Changes in the glycosylation pattern of the immunoglobulin G (IgG) Fc region are described for several diseases including meningococcal sepsis. In this study, we investigated the possible contribution of neutrophils and neutrophil implication, potentially related to degranulation or neutrophil extracellular trap (NET) formation in changing the IgG Fc N-glycosylation pattern in a murine sepsis model. We have measured the serum level of cytokines/chemokines and immunoglobulins, the serum activity of neutrophil elastase (NE), and analyzed the IgG Fc glycosylation pattern by Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (LC-ESI-MS) and Lectin enzyme-linked immunosorbent assay (ELISA). We observed an increased activity of NE- and neutrophil-associated cytokines such as keratinocyte chemoattractant (KC) with the development of sepsis. Regarding the IgG Fc N-glycosylation, we observed an increase in fucosylation and α1,3-galactosylation and a decrease for sialyation. Interestingly, these changes were not uniform for all IgG subclasses. After depletion of neutrophils, we saw a change in the exposure of fucose and α2,6-linked sialic acid during the time course of our experimental sepsis model. In conclusion, neutrophils can influence changes in the IgG glycosylation pattern in experimental sepsis.

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Clinical Mass Spectrometry Discovered Human IgG Sialylation as a Potential Biosignature for Kidney Function

Cited by 5 publications

References 27 publications

Association between immunoglobulin G N-glycosylation and lupus nephritis in female patients with systemic lupus erythematosus: a case-control study

Association between immunoglobulin G N-glycosylation and lupus nephritis in female patients with systemic lupus erythematosus: a case-control study

Definition of IgG Subclass-Specific Glycopatterns in Idiopathic Membranous Nephropathy: Aberrant IgG Glycoforms in Blood

Neutrophil Depletion Changes the N-Glycosylation Pattern of IgG in Experimental Murine Sepsis

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