IgG glycosylation in autoimmune diseases

Immunoglobulin G (IgG) is the most abundant glycoprotein in human serum. All IgG subclasses have a single-conserved N-linked glycosylation site at Asn297 of the heavy chain and 10–30% of IgGs are N-glycosylated also in a Fab region. N-glycans of Fc are sialylated and fucosylated biantennary complex-type structures. Glycosylation plays a key role in antibody function, and IgG N-glycans are essential for the proper activity of the immune system. Fc glycans are important for IgG effector functions, whereas Fab oligosaccharides modulate antigen binding. Glycosylation changes of IgG are associated with the development of various human diseases, including autoimmune states. The modification of one sugar moiety in N-glycan structure may result in the stimulation or suppression of immune response. The lack of core fucose leads to the enhancement of pro-inflammatory activity, whereas an increase of sialylation determines immunosuppressive properties of IgG. The contribution of IgG Fc glycosylation changes has been demonstrated in the pathogenesis of rheumatoid arthritis, lupus erythematosus and Crohn’s disease. A decrease in IgG galactosylation and sialylation, found in these diseases, activates effector cells and triggers inflammatory reactions. A detailed analysis of changes in IgG glycosylation and their effects on the development of autoimmune diseases is important in the treatment of these diseases. IgGs with modified α2,6-sialylation are used as therapeutic antibodies with anti-inflammatory properties. Numerous studies on IgG glycosylation have provided evidence of the role of this post-translational modification in the proper functioning of antibodies and the importance of changes in the structure of IgG glycans, mainly incomplete galactosylation and desialylation, in the pathogenesis of many diseases. The continuation of these studies may contribute to explaining the mechanisms of autoimmunity that is still poorly understood.

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Stem Cell Therapy and Regenerative Medicine in Autoimmune Diseases

10.5772/intechopen.89749 ◽

2021 ◽

Author(s):

Bhuvaneshwari Sampath ◽

Priyadarshan Kathirvelu ◽

Kavitha Sankaranarayanan

Keyword(s):

Stem Cell ◽

Immune System ◽

Regenerative Medicine ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Systemic Lupus ◽

Autoimmune Condition ◽

Recent Trends

The role of immune system in our body is to defense against the foreign bodies. However, if the immune system fails to recognize self and non-self-cells in our body leads to autoimmune diseases. Widespread autoimmune diseases are rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, and more yet to be added to the list. This chapter discusses about how stem cell-based therapies and advancement of regenerative medicine endow with novel treatment for autoimmune diseases. Furthermore, in detail, specific types of stem cells and their therapeutic approach for each autoimmune condition along with their efficiency to obtain desired results are discussed. Ultimately, this chapter describes the recent trends in treating autoimmune diseases effectively using advanced stem cell research.

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The Protective Role of HLA-DRB113 in Autoimmune Diseases

Journal of Immunology Research ◽

10.1155/2015/948723 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 23

Author(s):

Andreia Bettencourt ◽

Cláudia Carvalho ◽

Bárbara Leal ◽

Sandra Brás ◽

Dina Lopes ◽

...

Keyword(s):

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Genetic Background ◽

Protective Role ◽

Negative Association ◽

Thymic Selection ◽

Systemic Lupus ◽

Clonal Deletion ◽

Drb1 Locus

Autoimmune diseases (AIDs) are characterized by a multifactorial aetiology and a complex genetic background, with the MHC region playing a major role. We genotyped for HLA-DRB1 locus 1228 patients with AIDs-213 with Systemic Lupus Erythematosus (SLE), 166 with Psoriasis or Psoriatic Arthritis (Ps + PsA), 153 with Rheumatoid Arthritis (RA), 67 with Systemic Sclerosis (SSc), 536 with Multiple Sclerosis (MS), and 93 with Myasthenia Gravis (MG) and 282 unrelated controls. We confirmed previously established associations of HLA-DRB115 (OR = 2.17) and HLA-DRB103 (OR = 1.81) alleles with MS, HLA-DRB103 with SLE (OR = 2.49), HLA-DRB101 (OR = 1.79) and HLA-DRB104 (OR = 2.81) with RA, HLA-DRB107 with Ps + PsA (OR = 1.79), HLA-DRB101 (OR = 2.28) and HLA-DRB108 (OR = 3.01) with SSc, and HLA-DRB103 with MG (OR = 2.98). We further observed a consistent negative association of HLA-DRB113 allele with SLE, Ps + PsA, RA, and SSc (18.3%, 19.3%, 16.3%, and 11.9%, resp., versus 29.8% in controls). HLA-DRB113 frequency in the AIDs group was 20.0% (OR = 0.58). Although different alleles were associated with particular AIDs, the same allele, HLA-DRB113, was underrepresented in all of the six diseases analysed. This observation suggests that this allele may confer protection for AIDs, particularly for systemic and rheumatic disease. The protective effect of HLA-DRB113 could be explained by a more proficient antigen presentation by these molecules, favouring efficient clonal deletion during thymic selection.

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The Role of Th17 in Neuroimmune Disorders: Target for CAM Therapy. Part I

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nep062 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Aristo Vojdani ◽

Jama Lambert

Keyword(s):

Autoimmune Diseases ◽

Signaling Pathways ◽

Allergic Inflammation ◽

T Helper ◽

T Helper 1 ◽

T Helper 17 ◽

Effector Cells ◽

Pathogenic Factors ◽

T Helper 17 Cell

CD4+effector cells, based on cytokine production, nuclear receptors and signaling pathways, have been categorized into four subsets. T-helper-1 cells produce IFN-γ, TNF-β, lymphotoxin and IL-10; T-helper-2 cells produce IL-4, IL-5, IL-10, IL-13, IL-21 and IL-31; T-helper-3, or regulatory T-cells, produce IL-10, TGF-βand IL-35; and the recently discovered T-helper-17 cell produces IL-17, IL-17A, IL-17F, IL-21, IL-26 and CCL20. By producing IL-17 and other signaling molecules, Th17 contributes to the pathogenesis of multiple autoimmune diseases including allergic inflammation, rheumatoid arthritis, autoimmune gastritis, inflammatory bowel disease, psoriasis and multiple sclerosis. In this article, we review the differential regulation of inflammation in different tissues with a major emphasis on enhancement of neuroinflammation by local production of IL-17 in the brain. By understanding the role of pathogenic factors in the induction of autoimmune diseases by Th17 cells, CAM practitioners will be able to design CAM therapies targeting Th17 and associated cytokine activities and signaling pathways to repair the intestinal and blood-brain barriers for their patients with autoimmunities, in particular, those with neuroinflammation and neurodegeneration.

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The Histone Modification Code in the Pathogenesis of Autoimmune Diseases

Mediators of Inflammation ◽

10.1155/2017/2608605 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 27

Author(s):

Yasuto Araki ◽

Toshihide Mimura

Keyword(s):

Autoimmune Diseases ◽

Histone Modifications ◽

Lupus Erythematosus ◽

Cell Types ◽

Biliary Cirrhosis ◽

Loss Of Self ◽

Self Tolerance ◽

Different Cell Types

Autoimmune diseases are chronic inflammatory disorders caused by a loss of self-tolerance, which is characterized by the appearance of autoantibodies and/or autoreactive lymphocytes and the impaired suppressive function of regulatory T cells. The pathogenesis of autoimmune diseases is extremely complex and remains largely unknown. Recent advances indicate that environmental factors trigger autoimmune diseases in genetically predisposed individuals. In addition, accumulating results have indicated a potential role of epigenetic mechanisms, such as histone modifications, in the development of autoimmune diseases. Histone modifications regulate the chromatin states and gene transcription without any change in the DNA sequence, possibly resulting in phenotype alteration in several different cell types. In this paper, we discuss the significant roles of histone modifications involved in the pathogenesis of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary biliary cirrhosis, and type 1 diabetes.

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Schistosoma mansoni: larval damage and role of effector cell(s) in the synergy between vaccine immunity and Praziquantel treatment

Parasitology ◽

10.1017/s0031182000059497 ◽

1991 ◽

Vol 103 (2) ◽

pp. 207-224 ◽

Cited By ~ 5

Author(s):

K. P. Piper ◽

R. F. Mott ◽

D. J. Hockley ◽

D. J. McLaren

Keyword(s):

Effector Cell ◽

Inflammatory Reactions ◽

Effector Cells ◽

Ultrastructural Studies ◽

Praziquantel Treatment ◽

Internal Disruption ◽

Lung Worms ◽

Extent Of Damage

A number of authors have demonstrated that the schistosomicidal compound, Praziquantel (Pzq), depends for its action upon the immune status of the host (Sabah et al. 1985; Brindley & Sher, 1987; Doenhoff et al. 1987). We have attempted to define the synergistic interaction between immuno- and chemotherapy further, using the murine irradiated vaccine model of schistosomiasis mansoni. In vaccinated mice, resistance operates in the skin but not the lungs; drug targeted towards lung-stage worms exacerbates lung-phase immunity, however, as depicted by the increased number and size of inflammatory reactions in the pulmonary tissues. Parasites are often found trapped within such foci. In the present investigation, light and ultrastructural studies have been utilized to examine the nature and extent of damage inflicted upon lung-stage larvae recovered from day 6 Pzq-treated vaccinated mice. Such studies have revealed that damage involves muscle disorganization, internal disruption and occasionally, loss of the tegument; in the latter case, cells are often seen attached to the denuded lung worms. To identify the crucial cellular effector cell(s) involved in the synergy between immuno- and chemotherapy, cell depletion studies have been performed in vivo. It would appear from these experiments that eosinophils or lymphocytes rather than neutrophils or macrophages are important effector cells in this synergy. Histological studies argue in favour of eosinophils being the key effector cells.

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A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis

Clinical and Developmental Immunology ◽

10.1155/2011/305656 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Mie Oki ◽

Norihiko Watanabe ◽

Takayoshi Owada ◽

Yoshihiro Oya ◽

Kei Ikeda ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Autoimmune Diseases ◽

T Lymphocyte ◽

Lupus Erythematosus ◽

Susceptibility Gene ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Immunological Homeostasis ◽

Deficient Mice

Inhibitory coreceptors are thought to play important roles in maintaining immunological homeostasis, and a defect in the negative signals from inhibitory coreceptors may lead to the development of autoimmune diseases. We have recently identified B and T lymphocyte attenuator (BTLA), a new inhibitory coreceptor expressed on immune cells, and we suggest that BTLA may be involved in the development of autoimmune diseases using BTLA-deficient mice. However, the role of BTLA in the pathogenesis of autoimmune diseases in humans remains unknown. We, therefore, examined the possible association between BTLA and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS) by conducting a case-control genetic association study. We found that 590C single-nucleotide polymorphism (SNP) of BTLA gene was significantly associated with susceptibility to RA, but not to SLE or SS. Furthermore, RA patients bearing this 590C SNP developed the disease significantly earlier than the patients without this allele. We also found that BTLA with 590C allele lacked the inhibitory activity on concanavalin A- and anti-CD3 Ab-induced IL-2 production in Jurkat T cells. These results suggest that BTLA is an RA-susceptibility gene and is involved in the protection from autoimmunity in humans.

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Citrullination and PAD Enzyme Biology in Type 1 Diabetes – Regulators of Inflammation, Autoimmunity, and Pathology

Frontiers in Immunology ◽

10.3389/fimmu.2021.678953 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mei-Ling Yang ◽

Fernanda M. C. Sodré ◽

Mark J. Mamula ◽

Lut Overbergh

Keyword(s):

Rheumatoid Arthritis ◽

Type 1 Diabetes ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Nod Mice ◽

Neutrophil Extracellular Trap ◽

Comprehensive Overview ◽

General Role

The generation of post-translational modifications (PTMs) in human proteins is a physiological process leading to structural and immunologic variety in proteins, with potentially altered biological functions. PTMs often arise through normal responses to cellular stress, including general oxidative changes in the tissue microenvironment and intracellular stress to the endoplasmic reticulum or immune-mediated inflammatory stresses. Many studies have now illustrated the presence of ‘neoepitopes’ consisting of PTM self-proteins that induce robust autoimmune responses. These pathways of inflammatory neoepitope generation are commonly observed in many autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and type 1 diabetes (T1D), among others. This review will focus on one specific PTM to self-proteins known as citrullination. Citrullination is mediated by calcium-dependent peptidylarginine deiminase (PAD) enzymes, which catalyze deimination, the conversion of arginine into the non-classical amino acid citrulline. PADs and citrullinated peptides have been associated with different autoimmune diseases, notably with a prominent role in the diagnosis and pathology of rheumatoid arthritis. More recently, an important role for PADs and citrullinated self-proteins has emerged in T1D. In this review we will provide a comprehensive overview on the pathogenic role for PADs and citrullination in inflammation and autoimmunity, with specific focus on evidence for their role in T1D. The general role of PADs in epigenetic and transcriptional processes, as well as their crucial role in histone citrullination, neutrophil biology and neutrophil extracellular trap (NET) formation will be discussed. The latter is important in view of increasing evidence for a role of neutrophils and NETosis in the pathogenesis of T1D. Further, we will discuss the underlying processes leading to citrullination, the genetic susceptibility factors for increased recognition of citrullinated epitopes by T1D HLA-susceptibility types and provide an overview of reported autoreactive responses against citrullinated epitopes, both of T cells and autoantibodies in T1D patients. Finally, we will discuss recent observations obtained in NOD mice, pointing to prevention of diabetes development through PAD inhibition, and the potential role of PAD inhibitors as novel therapeutic strategy in autoimmunity and in T1D in particular.

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The essential role of costimulatory molecules in systemic lupus erythematosus

Lupus ◽

10.1177/0961203319829818 ◽

2019 ◽

Vol 28 (5) ◽

pp. 575-582 ◽

Cited By ~ 8

Author(s):

Z X Xiao ◽

N Olsen ◽

S G Zheng

Keyword(s):

Systemic Lupus Erythematosus ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Biological Effects ◽

Critical Role ◽

Chronic Inflammatory Disease ◽

Costimulatory Molecules ◽

Systemic Lupus ◽

System Disorder

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with immune system disorder mediated through complex autoimmune pathways that involve immune cells, nonimmune cells, cytokines, chemokines, as well as costimulatory molecules. Costimulatory signals play a critical role in initiating, maintaining and regulating immune reactions, and these include ligands and receptors and their interactions involving multiple types of signal information. Dysfunction of costimulatory factors results in complicated abnormal immune responses, with biological effects and eventually, clinical autoimmune diseases. Here we outline what is known about various roles that costimulatory families including the B7 family and tumor necrosis factor super family play in SLE. The aim of this review is to understand the possible association of costimulation with autoimmune diseases, especially SLE, and to explore possible therapeutic target(s) of costimulatory molecules and pathways that might be used to develop therapeutic approaches for patients with these conditions.

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Dietary Habits Bursting into the Complex Pathogenesis of Autoimmune Diseases: The Emerging Role of Salt from Experimental and Clinical Studies

Nutrients ◽

10.3390/nu11051013 ◽

2019 ◽

Vol 11 (5) ◽

pp. 1013 ◽

Cited By ~ 5

Author(s):

Rossana Scrivo ◽

Carlo Perricone ◽

Alessio Altobelli ◽

Chiara Castellani ◽

Lorenzo Tinti ◽

...

Keyword(s):

Environmental Factors ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Clinical Studies ◽

Dietary Habits ◽

Salt Intake ◽

Experimental Models ◽

Fine Tuning ◽

Current Evidence

The incidence and prevalence of autoimmune diseases have increased in Western countries over the last years. The pathogenesis of these disorders is multifactorial, with a combination of genetic and environmental factors involved. Since the epidemiological changes cannot be related to genetic background, which did not change significantly in that time, the role of environmental factors has been reconsidered. Among these, dietary habits, and especially an excessive salt, typical of processed foods, has been implicated in the development of autoimmune diseases. In this review, we summarize current evidence, deriving both from experimental models and clinical studies, on the capability of excessive salt intake to exacerbate proinflammatory responses affecting the pathogenesis of immune-mediated diseases. Data on several diseases are presented, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and Crohn’s disease, with many of them supporting a proinflammatory effect of salt. Likewise, a hypertonic microenvironment showed similar effects in experimental models both in vivo and in vitro. However, murine models of spontaneous autoimmune polyneuropathy exposed to high salt diet suggest opposite outcomes. These results dictate the need to further analyse the role of cooking salt in the treatment and prevention of autoimmune diseases, trying to shape a fine tuning between the possible advantages of a restricted salt intake and the changes in circulating metabolites, mediators, and hormones which come along salt consumption and could in turn influence autoimmunity.

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The Role of Mitochondria in Systemic Lupus Erythematosus: A Glimpse of Various Pathogenetic Mechanisms

Current Medicinal Chemistry ◽

10.2174/0929867326666181126165139 ◽

2020 ◽

Vol 27 (20) ◽

pp. 3346-3361 ◽

Cited By ~ 9

Author(s):

Shi-Kun Yang ◽

Hao-Ran Zhang ◽

Shu-Peng Shi ◽

Ying-Qiu Zhu ◽

Na Song ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Mitochondrial Dysfunction ◽

Lupus Erythematosus ◽

Mitochondrial Dynamics ◽

Therapeutic Targets ◽

High Recurrence Rate ◽

Systemic Lupus ◽

Inflammatory Reactions ◽

Novel Therapeutic

Background: Systemic Lupus Erythematosus (SLE) is a polysystem autoimmune disease that adversely affects human health. Various organs can be affected, including the kidney or brain. Traditional treatment methods for SLE primarily rely on glucocorticoids and immunosuppressors. Unfortunately, these therapeutic agents cannot prevent a high recurrence rate after SLE remission. Therefore, novel therapeutic targets are urgently required. Methods: A systematic search of the published literature regarding the abnormal structure and function of mitochondria in SLE and therapies targeting mitochondria was performed in several databases. Results: Accumulating evidence indicates that mitochondrial dysfunction plays important roles in the pathogenesis of SLE, including influencing mitochondrial DNA damage, mitochondrial dynamics change, abnormal mitochondrial biogenesis and energy metabolism, mitophagy, oxidative stress, inflammatory reactions, apoptosis and NETosis. Further investigation of mitochondrial pathophysiological roles will result in further clarification of SLE. Specific lupus-induced organ damage also exhibits characteristic mitochondrial changes. Conclusion: This review aimed to summarize the current research on the role of mitochondrial dysfunction in SLE, which will necessarily provide potential novel therapeutic targets for SLE.

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