Changes of Serum IgG Glycosylation Patterns in Primary Biliary Cholangitis Patients

Zeng, Xiaoli; Li, Siting; Tang, Shiyi; Li, Xi; Zhang, Jianan; Li, Mengtao; Zeng, Xiaofeng; Hu, Chao

doi:10.3389/fimmu.2021.669137

Cited by 17 publications

(16 citation statements)

References 61 publications

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“…Galβ3GalNAc is a part of O-glycosylation, whose function has not been fully elucidated due to its complicated structure and resistance to proteolytic digestion [ 25 ]. Nevertheless, its alteration has been reported in some diseases [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

IgG Glycosylation Profiling of Peripheral Artery Diseases with Lectin Microarray

Meng

et al. 2022

JCM

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Background: Inflammation plays a key role in the progression of atherosclerotic plaque for peripheral artery disease (PAD). Immunoglobulin G (IgG) glycosylation could modulate immunological effector functions and has been explored as biomarkers for various diseases. Methods: Lectin microarray was applied to analyze the expression profile of serum IgG glycosylation in patients with lower-extremity peripheral artery disease (LEPAD), carotid artery stenosis (CAS), abdominal aortic aneurysm (AAA), and healthy controls. Lectin blot was performed to validate the differences. Results: SNA (Sambucus nigra agglutinin) binding (preferred sialic acid) was significantly higher in the LEPAD (3.21 ± 2.06) and AAA (3.34 ± 2.42) groups compared to the CAS (2.47 ± 1.45) group. Significantly higher binding levels of ConA (Concanavalin A) (preferred mannose) and PSA (Pisum sativum agglutinin) (preferred fucose) were also observed in LEPAD compared to CAS patients. Among LEPAD patients, a significant lower binding level of Black bean crude (preferred GalNAc) was present for dyslipidemia patients. A higher binding level of MNA-M (Morniga M agglutinin) (preferred Mannose) and Jacalin-AIA (Artocarpus integrifolia agglutinin) (preferred Galβ3GalNAc) was observed for Fontaine severe patients. Higher binding levels of PHA-E (Phaseolus vulgaris Erythroagglutinin) and PHA-L (Phaseolus vulgaris Leucoagglutinin) (preferred Galβ4GlcNAc) were observed for diabetic patients, and higher binding of ASA (Allium sativum agglutinin) (preferred Mannose) was present in patients with hypertension. The level of high-sensitivity C-reactive protein (hsCRP) was positively associated with LTL (Lotus tetragonolobus lectin) (r = 0.44), PSA (r = 0.44), LCA (Lens Culinaris agglutinin) (r = 0.39), SNA (r = 0.57), and CSA (Cytisus sscoparius agglutinin) (r = 0.56). For CAS, symptomatic patients had lower binding levels of AAL (Aleuria aurantia lectin) (preferred fucose) and IAA (Iberis amara agglutinin) (preferred GalNAc). Blood total cholesterol level was positively associated with SNA-I (r = 0.36) and SBA (Soybean agglutinin) (r = 0.35). Creatinine levels were positively associated with lectins including, but not limited to, MNA-M (r = 0.42), CSA (r = 0.45), GHA (Glechoma hederacea agglutinin) (r = 0.42), and MNA-G (Morniga G agglutinin) (r = 0.45). Conclusion: LEPAD patients had increased IgG binding levels of SNA and ConA compared to CAS, which could provide potential diagnostic value. Fontaine severity was associated with Mannose-rich IgG N-glycan, while diabetic LEPAD correlated with bisecting GlcNAc. The levels of hsCRP and creatinine were positively associated with IgG fucosylation and galactosylation. Changes in IgG glycosylation may play important roles in PAD pathogenesis and progression.

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Section: Discussionmentioning

confidence: 99%

IgG Glycosylation Profiling of Peripheral Artery Diseases with Lectin Microarray

Meng

et al. 2022

JCM

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“…Most therapeutic antibodies that are currently available are developed in the IgG framework; the majority of which belong to the IgG1 subtype [ 67 , 68 ]. IgG1 has a 60% abundance distribution in the serum and primarily binds protein antigens, is highly stable and resistant to aggregation, and has a greater ability to activate antibody-dependent cytotoxicity and complement-dependent cytotoxicity [ 69 , 70 ]. In contrast, another antibody fragment based on the IgG form, scFv-Fc, is similar to full-length IgG in terms of tumor uptake [ 66 ] and has a better tumor targeting profile.…”

Section: Discussionmentioning

confidence: 99%

Fully human recombinant antibodies against EphA2 from a multi-tumor patient immune library suitable for tumor-targeted therapy

Yang

Nian

et al. 2021

Bioengineered

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Enhanced EphA2 expression is observed in a variety of epithelial-derived malignancies and is an important target for anti-tumor therapy. Currently, Therapeutic monoclonal antibodies against immune checkpoints have shown good efficacy for tumor treatment. In this study, we constructed an immune single-chain fragment variable (scFv) library using peripheral blood mononuclear cells (PBMCs) from 200 patients with a variety of malignant tumors. High affinity scFvs against EphA2 can be easily screened from the immune library using phage display technology. Anti-EphA2 scFvs can be modified into any form of recombinant antibody, including scFv-Fc and full-length IgG1 antibodies, and the recombinant antibody affinity was improved following modification. Among the modified anti-EphA2 antibodies the affinity of 77-IgG1 was significantly increased, reaching a pmol affinity level (10 −12 ). We further demonstrated the binding activity of recombinant antibodies to the EphA2 protein, tumor cells, and tumor tissues using macromolecular interaction techniques, flow cytometry and immunohistochemistry. Most importantly, both the constructed scFvs-Fc, as well as the IgG1 antibodies against EphA2 were able to inhibit the growth of tumor cells to some extent. These results suggest that the immune libraries from patients with malignant tumors are more likely to screen for antibodies with high affinity and therapeutic effect. The constructed fully human scFv immune library has broad application prospects for specific antibody screening. The screened scFv-Fc and IgG1 antibodies against EphA2 can be used for the further study of tumor immunotherapy.

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“…Our previous study applied a lectin microarray to explore the glycosylation of IgG4 in IgG4 related diseases (IgG4-RD) and found that specific glycan levels can be used as predictors of multiple organ damage and assessment of disease activity (19). In addition, we also used the microarray to detect the unique glycan levels in patients with primary biliary cholangitis (PBC), and IgG glycosylation patterns were observed to be associated with the positivity of different PBC specific autoantibodies (20). Our researches demonstrated that lectin microarray can provide a powerful tool for the pathogenesis and clinical practices of autoimmune diseases.…”

Section: Introductionmentioning

confidence: 95%

Association of the serum IgG glycosylation with disease activity of anti-transcription intermediary factor 1 gamma positive dermatomyositis

Bai

et al. 2022

Clinical and Experimental Rheumatology

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ObjectiveDermatomyositis (DM) is an idiopathic inflammatory myopathy characterised by the presence of a variety of myositis-specific autoantibodies (MSA) in the circulation. As one of the commonly-detected MSA, anti-transcription intermediary factor 1 gamma (TIF1γ) autoantibody is strongly associated with DM-related malignancy and disease activity. We investigated the glycosylation patterns of serum IgG and to determine the clinical significance of specific glycosylation patterns in patients with anti-TIF1γ positive DM. Methods Lectin microarray was used to reveal the glycosylation patterns of serum IgG among 52 DM, 46 disease controls (DC) and 49 healthy controls (HC). Lectin blot was used to further validate the specific alteration of glycosylation. The correlationbetween glycan levels and clinical features was also evaluated. ResultsThe results of lectin microarray showed that compared with the DC group, the DM group had significantly lower glycan levels of mannose and glucose. Compared with the HC group, the glycans levels of GalNAc, galactose, Galβ3GalNAc, sialic acid, and fucose were observed significantly higher in DM group. Lectin blot demonstrated that anti-TIF1γ positive DM had lower glycan level of GlcNAc (recognized by LEL) compared to patients with MSA negative DM, DC, and HC groups. Additionally, the glycan level of GlcNAc was positively associated with manual muscle test (r=0.547, p=0.028), or negatively associated with p=0.049) and disease activity score (r=-0.507, p=0.045). ConclusionAnti-TIF1γ positive DM presents a unique glycosylation pattern in serum IgG. Considering that the glycan level of GlcNAc reflects the inflammatory state and disease activity, glycosylation has a role in clinical utility by monitoring disease in patients with anti-TIF1γ positive DM.

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Changes of Serum IgG Glycosylation Patterns in Primary Biliary Cholangitis Patients

Cited by 17 publications

References 61 publications

IgG Glycosylation Profiling of Peripheral Artery Diseases with Lectin Microarray

IgG Glycosylation Profiling of Peripheral Artery Diseases with Lectin Microarray

Fully human recombinant antibodies against EphA2 from a multi-tumor patient immune library suitable for tumor-targeted therapy

Association of the serum IgG glycosylation with disease activity of anti-transcription intermediary factor 1 gamma positive dermatomyositis

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