The Protective Role of HLA-DRB113 in Autoimmune Diseases

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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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 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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The curious case of miR-155 in SLE

Expert Reviews in Molecular Medicine ◽

10.1017/erm.2021.11 ◽

2021 ◽

Vol 23 ◽

Author(s):

S. A. Ibrahim ◽

A. Y. Afify ◽

I. O. Fawzy ◽

N. El-Ekiaby ◽

A. I. Abdelaziz

Keyword(s):

Systemic Lupus Erythematosus ◽

Immune System ◽

Targeted Therapy ◽

Animal Models ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Systemic Lupus ◽

Recent Attention ◽

Made In

Abstract Epigenetic modifications have been well documented in autoimmune diseases. MicroRNAs (miRNAs), in particular, have long intrigued scientists in the field of autoimmunity. Owing to its central role in the development of the immune system, microRNA-155 (miR-155) is deeply involved in systemic lupus erythematosus (SLE). Despite the advancements made in treating SLE, the disease still remains incurable. Therefore, recent attention has been drawn to the manipulation of epigenetics in the development of curative treatments. In fact, it is a widely held view that miRNA-targeted therapy is a new glimmer of hope in the treatment of autoimmune diseases. However, the duplicity of miRNAs should not be overlooked. A single miRNA can target several mRNAs, and some mRNAs may possess opposing functions. In this review, we highlight the role of miR-155 as a biomarker and review its functions in SLE patients and animal models while discussing possible reasons behind inconsistencies across studies.

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Signaling Pathways of Type I and Type III Interferons and Targeted Therapies in Systemic Lupus Erythematosus

Cells ◽

10.3390/cells8090963 ◽

2019 ◽

Vol 8 (9) ◽

pp. 963 ◽

Cited By ~ 10

Author(s):

I-Tsu Chyuan ◽

Hong-Tai Tzeng ◽

Ji-Yih Chen

Keyword(s):

Systemic Lupus Erythematosus ◽

Autoimmune Diseases ◽

Signaling Pathways ◽

Lupus Erythematosus ◽

Janus Kinase ◽

Type I ◽

Systemic Lupus ◽

Type Iii ◽

Signature Genes

Type I and type III interferons (IFNs) share several properties in common, including the induction of signaling pathways, the activation of gene transcripts, and immune responses, against viral infection. Recent advances in the understanding of the molecular basis of innate and adaptive immunity have led to the re-examination of the role of these IFNs in autoimmune diseases. To date, a variety of IFN-regulated genes, termed IFN signature genes, have been identified. The expressions of these genes significantly increase in systemic lupus erythematosus (SLE), highlighting the role of type I and type III IFNs in the pathogenesis of SLE. In this review, we first discussed the signaling pathways and the immunoregulatory roles of type I and type III IFNs. Next, we discussed the roles of these IFNs in the pathogenesis of autoimmune diseases, including SLE. In SLE, IFN-stimulated genes induced by IFN signaling contribute to a positive feedback loop of autoimmunity, resulting in perpetual autoimmune inflammation. Based on this, we discussed the use of several specific IFN blocking strategies using anti-IFN-α antibodies, anti-IFN-α receptor antibodies, and IFN-α-kinoid or downstream small molecules, which intervene in Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways, in clinical trials for SLE patients. Hopefully, the development of novel regimens targeting IFN signaling pathways will shed light on promising future therapeutic applications for SLE patients.

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How Does Age at Onset Influence the Outcome of Autoimmune Diseases?

Autoimmune Diseases ◽

10.1155/2012/251730 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 13

Author(s):

Manuel J. Amador-Patarroyo ◽

Alberto Rodriguez-Rodriguez ◽

Gladis Montoya-Ortiz

Keyword(s):

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Age At Onset ◽

Early Age ◽

Systemic Lupus ◽

Course Of Disease ◽

Mortality And Morbidity ◽

Time Period

The age at onset refers to the time period at which an individual experiences the first symptoms of a disease. In autoimmune diseases (ADs), these symptoms can be subtle but are very relevant for diagnosis. They can appear during childhood, adulthood or late in life and may vary depending on the age at onset. Variables like mortality and morbidity and the role of genes will be reviewed with a focus on the major autoimmune disorders, namely, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes mellitus (T1D), Sjögren's syndrome, and autoimmune thyroiditis (AITD). Early age at onset is a worst prognostic factor for some ADs (i.e., SLE and T1D), while for others it does not have a significant influence on the course of disease (i.e., SS) or no unanimous consensus exists (i.e., RA and MS).

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Role of Dendritic Cells in the Rheumatic Diseases Pathogenesis: Review

Annals of the Russian academy of medical sciences ◽

10.15690/vramn1486 ◽

2021 ◽

Vol 76 (4) ◽

pp. 394-401

Author(s):

Yuliya D. Kurochkina ◽

Maxim A. Korolev

Keyword(s):

Rheumatoid Arthritis ◽

Dendritic Cells ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Systemic Lupus ◽

Functional Features ◽

Antigen Presenting ◽

Methods Of Treatment ◽

Existing Data

Dendritic cells (DCs) are professional antigen presenting cells that can as stimulate immune response as suppress immune inflamma tion. Recently the role of DCs in the pathogenesis of autoimmune diseases and the possibility of their application as diagnostic markers and methods of treatment has been studied more and more. It was shown that subpopulations DCs play different role in pathogenesis various autoimmune diseases. Thus, pathogenesis of rheumatoid arthritis and ankylosing spondylitis is associated with activity of myeloid DCs and their possibility to present arthritogenic peptides to T-cells. While plasmocytoid DCs are more important in pathogenesis systemic lupus erythematosus and systemic sclerosis. The review presents the results of the latest registered clinical trials about applications DCs in different autoimmune diseases as well as current ideas about functional features DCs during autoimmune diseases. The existing data confirm their possible use as well as the safety of DC in treatment.

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B Cells in Autoimmune Diseases

Scientifica ◽

10.6064/2012/215308 ◽

2012 ◽

Vol 2012 ◽

pp. 1-18 ◽

Cited By ~ 45

Author(s):

Christiane S. Hampe

Keyword(s):

B Cells ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Germinal Centers ◽

Cellular Functions ◽

Systemic Lupus ◽

Reciprocal Interactions ◽

Selective Targeting

The role of B cells in autoimmune diseases involves different cellular functions, including the well-established secretion of autoantibodies, autoantigen presentation and ensuing reciprocal interactions with T cells, secretion of inflammatory cytokines, and the generation of ectopic germinal centers. Through these mechanisms B cells are involved both in autoimmune diseases that are traditionally viewed as antibody mediated and also in autoimmune diseases that are commonly classified as T cell mediated. This new understanding of the role of B cells opened up novel therapeutic options for the treatment of autoimmune diseases. This paper includes an overview of the different functions of B cells in autoimmunity; the involvement of B cells in systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes; and current B-cell-based therapeutic treatments. We conclude with a discussion of novel therapies aimed at the selective targeting of pathogenic B cells.

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Clinical and Pathological Roles of Ro/SSA Autoantibody System

Clinical and Developmental Immunology ◽

10.1155/2012/606195 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 39

Author(s):

Ryusuke Yoshimi ◽

Atsuhisa Ueda ◽

Keiko Ozato ◽

Yoshiaki Ishigatsubo

Keyword(s):

Systemic Lupus Erythematosus ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Clinical Importance ◽

Systemic Lupus ◽

Systemic Autoimmune Diseases ◽

Nuclear Antigens ◽

Diagnosis And Classification

Anti-Ro/SSA antibodies are among the most frequently detected autoantibodies against extractable nuclear antigens and have been associated with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). Although the presence of these autoantibodies is one of the criteria for the diagnosis and classification of SS, they are also sometimes seen in other systemic autoimmune diseases. In the last few decades, the knowledge of the prevalence of anti-Ro/SSA antibodies in various autoimmune diseases and symptoms has been expanded, and the clinical importance of these antibodies is increasing. Nonetheless, the pathological role of the antibodies is still poorly understood. In this paper, we summarize the milestones of the anti-Ro/SSA autoantibody system and provide new insights into the association between the autoantibodies and the pathogenesis of autoimmune diseases.

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