Sialylation as an Important Regulator of Antibody Function

Vattepu, Ravi; Sneed, Sunny Lyn; Anthony, Robert M.

doi:10.3389/fimmu.2022.818736

Cited by 51 publications

(38 citation statements)

References 191 publications

(207 reference statements)

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“…2 ). For example, the human IgG1 Fc region is glycosylated at the conserved Asn297 residue, and IgG1 antibodies in healthy adults are typically characterized by high levels of fucosylation (85–95%), intermediate levels of galactosylation (25–40%), low levels of bisection (5–15%) and low levels of sialylation (2–15%) 123 , 124 . The glycosylation pattern of IgG1 directly influences its affinity for FcγR.…”

Section: Features Of Antibodies To Sars-cov-2mentioning

confidence: 99%

Beyond neutralization: Fc-dependent antibody effector functions in SARS-CoV-2 infection

et al. 2022

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Neutralizing antibodies are known to have a crucial role in protecting against SARS-CoV-2 infection and have been suggested to be a useful correlate of protection for vaccine clinical trials and for population-level surveys. In addition to neutralizing virus directly, antibodies can also engage immune effectors through their Fc domains, including Fc receptor-expressing immune cells and complement. The outcome of these interactions depends on a range of factors, including antibody isotype–Fc receptor combinations, Fc receptor-bearing cell types and antibody post-translational modifications. A growing body of evidence has shown roles for these Fc-dependent antibody effector functions in determining the outcome of SARS-CoV-2 infection. However, measuring these functions is more complicated than assays that measure antibody binding and virus neutralization. Here, we examine recent data illuminating the roles of Fc-dependent antibody effector functions in the context of SARS-CoV-2 infection, and we discuss the implications of these data for the development of next-generation SARS-CoV-2 vaccines and therapeutics.

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Section: Features Of Antibodies To Sars-cov-2mentioning

confidence: 99%

Beyond neutralization: Fc-dependent antibody effector functions in SARS-CoV-2 infection

et al. 2022

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“…We found that serum IgG of LEPAD patients had a significantly higher binding level of SNA (preferred sialic acid), ConA (preferred mannose), and PSA (preferred fucose) compared to CAS, with results of SNA and ConA confirmed by lectin blot analysis. Sialylation of the IgG Fc domain has been found to impair the complement-dependent cytotoxicity (CDC) effect [ 21 ], a reduction of which has been observed during inflammation and autoimmune disease flares [ 22 ]. It has been reported that loss of sialic acid might contribute to ischemic stroke [ 23 ].…”

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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“…The removal of glycosylation abolishes FcR binding and antibody-dependent cellular cytotoxicity (ADCC). In particular, sialylation in the Fc domain elongates the half-life in serum [ 48 , 49 , 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Delivery of Drugs into Cancer Cells Using Antibody–Drug Conjugates Based on Receptor-Mediated Endocytosis and the Enhanced Permeability and Retention Effect

Tashima

2022

Antibodies

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Innumerable people worldwide die of cancer every year, although pharmaceutical therapy has actualized many benefits in human health. For background, anti-cancer drug development is difficult due to the multifactorial pathogenesis and complicated pathology of cancers. Cancer cells excrete hydrophobic low-molecular anti-cancer drugs by overexpressed efflux transporters such as multiple drug resistance 1 (MDR1) at the apical membrane. Mutation-driven drug resistance is also developed in cancer. Moreover, the poor distribution of drug to cancer cells is a serious problem, because patients suffer from off-target side effects. Thus, highly selective and effective drug delivery into solid cancer cells across the membrane should be established. It is known that substances (10–100 nm in diameter) such as monoclonal antibodies (mAbs) (approximately 14.2 nm in diameter) or nanoparticles spontaneously gather in solid tumor stroma or parenchyma through the capillary endothelial fenestration, ranging from 200–2000 nm, in neovasculatures due to the enhanced permeability and retention (EPR) effect. Furthermore, cancer antigens, such as HER2, Nectin-4, or TROP2, highly selectively expressed on the surface of cancer cells act as a receptor for receptor-mediated endocytosis (RME) using mAbs against such antigens. Thus, antibody–drug conjugates (ADCs) are promising anti-cancer pharmaceutical agents that fulfill accurate distribution due to the EPR effect and due to antibody–antigen binding and membrane permeability owing to RME. In this review, I introduce the implementation and possibility of highly selective anti-cancer drug delivery into solid cancer cells based on the EPR effect and RME using anti-cancer antigens ADCs with payloads through suitable linkers.

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Sialylation as an Important Regulator of Antibody Function

Cited by 51 publications

References 191 publications

Beyond neutralization: Fc-dependent antibody effector functions in SARS-CoV-2 infection

Beyond neutralization: Fc-dependent antibody effector functions in SARS-CoV-2 infection

IgG Glycosylation Profiling of Peripheral Artery Diseases with Lectin Microarray

Delivery of Drugs into Cancer Cells Using Antibody–Drug Conjugates Based on Receptor-Mediated Endocytosis and the Enhanced Permeability and Retention Effect

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