Antibody glycosylation in autoimmune diseases

Zhou, Xing; Motta, Francesca; Selmi, Carlo; Ridgway, William M.; Gershwin, M. Eric; Zhang, Weici

doi:10.1016/j.autrev.2021.102804

Cited by 37 publications

(27 citation statements)

References 155 publications

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“…Glycosylation, as a posttranslational modification of IgG, is critical for the modulation of the immune response to inflammation, including ADCC ( 41 ), CDC ( 42 ), antibody-dependent cellular phagocytosis (ADCP) ( 43 ), and antigen binding ( 4 ), and may act as a ‘switch’ to control the pathogenicity of IgG ( 15 ). In our study, we found that cytokines in the microenvironment promoted IgG secretion and changed the N-glycan patterns of IgG.…”

Section: Discussionmentioning

confidence: 99%

“…In our previous study, we found that the glycosylation levels of TgAb IgG were increased in patients with Hashimoto’s thyroiditis (HT) compared to healthy donors ( 9 , 10 ). Glycan patterns are not templated but remarkably dynamic and govern the biological functions of IgG by affecting its affinity to Fcγ receptors and C1q ( 11 – 14 ), leading to a wide range of immune responses ( 15 ). Therefore, carbohydrate structures are critical for modulating the biological functions of IgG in the execution phase of the immune response, and an investigation of the mechanisms underlying the effects of changes in IgG glycosylation could shed new light on the pathogenesis and progression of AIDs.…”

Section: Introductionmentioning

confidence: 99%

“…Elevations of various cytokines in both circulation and the site of inflammation have been reported in AIDs ( 15 , 26 ). An imbalance between T helper (Th)1 cells/Th2 cells and Th17 cells/Treg cells was reported to play a critical role in the breakdown of immune tolerance and prompt the development of AIDs with local production of cytokines (including IFN-γ, TNF-α, IL-21, and IL-17A), including RA, systemic lupus erythematosus (SLE), Sjogren’s syndrome (SS), and autoimmune thyroid diseases (AITD) ( 27 – 32 ).…”

Section: Introductionmentioning

confidence: 99%

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Cytokines in the Immune Microenvironment Change the Glycosylation of IgG by Regulating Intracellular Glycosyltransferases

et al. 2022

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BackgroundChanges in IgG glycosylation, as a novel pathological feature, are observed in various autoimmune diseases (AIDs). The glycosylation patterns of IgG play a critical role in regulating the biological function and stability of IgG involved in the pathophysiology of many AIDs. However, the intracellular regulatory mechanisms underlying the effects of disturbances in various cytokines on IgG glycosylation are poorly understood. Thus, we investigated the regulatory effects of elevated cytokines in AIDs on intracellular IgG glycosylation within B cells.MethodsFirst, we established a controlled primary culture system in vitro to differentiate human CD19+ B cells into antibody-secreting cells (ASCs). Then, the IgG concentrations in the supernatants were measured by enzyme-linked immunoassay (ELISA) under IFN-γ, TNF-α, IL-21, IL-17A, BAFF, or APRIL stimulation. Next, the glycosylation levels of IgG under different stimuli were compared via a lectin microarray. The fine carbohydrate structures of IgG were confirmed by matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS). Finally, the expression of glycosyltransferases and glycosidases in B cells under stimulation with several cytokines was detected by real-time PCR and western blotting.ResultsWe found that cytokines significantly promoted IgG production in vitro and led to considerably different IgG glycan patterns. Specifically, the results of lectin microarray showed the galactose level of IgG was increased by IFN-γ stimulation (p<0.05), and the sialylation of IgG was increased by IL-21 and IL-17A (p<0.05). The MALDI-TOF-MS data showed that the frequency of agalactosylation was decreased by IFN-γ with the increased frequency of mono-galactosylation and decreased frequency of digalactosylation, accompanied by upregulation of β-1,4-galactosyltransferase 1. Both frequencies of mono-sialylated and disialylated N-glycans were increased by IL-21 and IL-17A with decreased frequency of asialylation, and the expression of β-galactoside α-2,6-sialyltransferase 1 was upregulated by IL-21 and IL-17A.ConclusionAbnormally elevated cytokines in the microenvironment regulates IgG glycan patterns by regulating intracellular glycosyltransferases in human B cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cytokines in the Immune Microenvironment Change the Glycosylation of IgG by Regulating Intracellular Glycosyltransferases

et al. 2022

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“…N-linked glycans play an important role in immunity and, in autoimmune disease, the severity of the response to autoantibodies can be modulated by the degree of glycosylation on the Fc or variable domain (Fab) of immunoglobulins [ 113 ]. Several studies demonstrated that glycosylation patterns of ACPAs modulate their pathogenicity and change during autoimmune disease progression.…”

Section: Protein Citrullination As a Hallmark Of Immune Disordersmentioning

confidence: 99%

Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives

Ciesielski

Biesiekierska

Panthu

et al. 2022

Cell. Mol. Life Sci.

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Numerous post-translational modifications (PTMs) govern the collective metabolism of a cell through altering the structure and functions of proteins. The action of the most prevalent PTMs, encompassing phosphorylation, methylation, acylations, ubiquitination and glycosylation is well documented. A less explored protein PTM, conversion of peptidylarginine to citrulline, is the subject of this review. The process of citrullination is catalysed by peptidylarginine deiminases (PADs), a family of conserved enzymes expressed in a variety of human tissues. Accumulating evidence suggest that citrullination plays a significant role in regulating cellular metabolism and gene expression by affecting a multitude of pathways and modulating the chromatin status. Here, we will discuss the biochemical nature of arginine citrullination, the enzymatic machinery behind it and also provide information on the pathological consequences of citrullination in the development of inflammatory diseases (rheumatoid arthritis, multiple sclerosis, psoriasis, systemic lupus erythematosus, periodontitis and COVID-19), cancer and thromboembolism. Finally, developments on inhibitors against protein citrullination and recent clinical trials providing a promising therapeutic approach to inflammatory disease by targeting citrullination are discussed.

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“…( 121 ); and Zhou et al. ( 129 )]. For example, COPD patients have more complex glycan structures and a decrease in monogalactosylated species compared to healthy individuals ( 130 ).…”

Section: Potential Mechanisms Of Graft Injury By Pre-existing Autoantibodiesmentioning

confidence: 99%

Set Up for Failure: Pre-Existing Autoantibodies in Lung Transplant

et al. 2021

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Lung transplant patients have the lowest long-term survival rates compared to other solid organ transplants. The complications after lung transplantation such as primary graft dysfunction (PGD) and ultimately chronic lung allograft dysfunction (CLAD) are the main reasons for this limited survival. In recent years, lung-specific autoantibodies that recognize non-HLA antigens have been hypothesized to contribute to graft injury and have been correlated with PGD, CLAD, and survival. Mounting evidence suggests that autoantibodies can develop during pulmonary disease progression before lung transplant, termed pre-existing autoantibodies, and may participate in allograft injury after transplantation. In this review, we summarize what is known about pulmonary disease autoantibodies, the relationship between pre-existing autoantibodies and lung transplantation, and potential mechanisms through which pre-existing autoantibodies contribute to graft injury and rejection.

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Antibody glycosylation in autoimmune diseases

Cited by 37 publications

References 155 publications

Cytokines in the Immune Microenvironment Change the Glycosylation of IgG by Regulating Intracellular Glycosyltransferases

Cytokines in the Immune Microenvironment Change the Glycosylation of IgG by Regulating Intracellular Glycosyltransferases

Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives

Set Up for Failure: Pre-Existing Autoantibodies in Lung Transplant

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