scholarly journals Antigen Microarrays for the Study of Autoimmune Diseases

2013 ◽  
Vol 59 (7) ◽  
pp. 1036-1044 ◽  
Author(s):  
Ada Yeste ◽  
Francisco J Quintana
Keyword(s):  
Immune Response ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Disease Diagnosis ◽  
Autoimmune Disorders ◽  
Response To Therapy ◽  
Autoimmune Response ◽  
Molecular Pathways ◽  
Systemic Lupus

BACKGROUND The immune response involves the activation of heterogeneous populations of T cells and B cells that show different degrees of affinity and specificity for target antigens. Although several techniques have been developed to study the molecular pathways that control immunity, there is a need for high-throughput assays to monitor the specificity of the immune response. CONTENT Antigen microarrays provide a new tool to study the immune response. We reviewed the literature on antigen microarrays and their advantages and limitations, and we evaluated their use for the study of autoimmune diseases. Antigen arrays have been successfully used for several purposes in the investigation of autoimmune disorders: for disease diagnosis, to monitor disease progression and response to therapy, to discover mechanisms of pathogenesis, and to tailor antigen-specific therapies to the autoimmune response of individual patients. In this review we discuss the use of antigen microarrays for the study of 4 common autoimmune diseases and their animal models: type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. CONCLUSIONS Antigen microarrays constitute a new tool for the investigation of the immune response in autoimmune disorders and also in other conditions such as tumors and allergies. Once current limitations are overcome, antigen microarrays have the potential to revolutionize the investigation and management of autoimmune diseases.

scholarly journals Stem Cell Therapy and Regenerative Medicine in Autoimmune Diseases

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.

scholarly journals A Novel Method for Real-Time, Continuous, Fluorescence-Based Analysis of Anti-DNA Abzyme Activity in Systemic Lupus

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Michelle F. Cavallo ◽  
Anna M. Kats ◽  
Ran Chen ◽  
James X. Hartmann ◽  
Mirjana Pavlovic
Keyword(s):  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Hydrolytic Activity ◽  
Disease Diagnosis ◽  
Response To Therapy ◽  
Systemic Lupus ◽  
Lupus Pathogenesis ◽  
Indirect Identification ◽  
Dna Antibodies ◽  
Novel Method

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the production of antibodies against a variety of self-antigens including nucleic acids. These antibodies are cytotoxic, catalytic (hydrolyzing DNA, RNA, and protein), and nephritogenic. Current methods for investigating catalytic activities of natural abzymes produced by individuals suffering from autoimmunity are mostly discontinuous and often employ hazardous reagents. Here we demonstrate the utility of dual-labeled, fluorogenic DNA hydrolysis probes in highly specific, sensitive, continuous, fluorescence-based measurement of DNA hydrolytic activity of anti-ssDNA abzymes purified from the serum of patients suffering from SLE. An assay for the presence and levels of antibodies exhibiting hydrolytic activity could facilitate disease diagnosis, prediction of flares, monitoring of disease state, and response to therapy. The assay may allow indirect identification of additional targets of anti-DNA antibodies and the discovery of molecules that inhibit their activity. Combined, these approaches may provide new insights into molecular mechanisms of lupus pathogenesis.

scholarly journals The peptide symporter SLC15a4 is essential for the development of systemic lupus erythematosus in murine models

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244439
Author(s):  
Arna Katewa ◽  
Eric Suto ◽  
Jessica Hui ◽  
Jose Heredia ◽  
Jie Liang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Response ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Pharmacological Intervention ◽  
Systemic Lupus ◽  
Autoantibody Production ◽  
Type 1 Interferon ◽  
Cell Functions

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease representing a serious unmet medical need. The disease is associated with the loss of self-tolerance and exaggerated B cell activation, resulting in autoantibody production and the formation of immune complexes that accumulate in the kidney, causing glomerulonephritis. TLR7, an important mediator of the innate immune response, drives the expression of type-1 interferon (IFN), which leads to expression of type-1 IFN induced genes and aggravates lupus pathology. Because the lysosomal peptide symporter slc15a4 is critically required for type-1 interferon production by pDC, and for certain B cell functions in response to TLR7 and TLR9 signals, we considered it as a potential target for pharmacological intervention in SLE. We deleted the slc15a4 gene in C57BL/6, NZB, and NZW mice and found that pristane-challenged slc15a4-/- mice in the C57BL/6 background and lupus prone slc15a4-/- NZB/W F1 mice were both completely protected from lupus like disease. In the NZB/W F1 model, protection persisted even when disease development was accelerated with an adenovirus encoding IFNα, emphasizing a broad role of slc15a4 in disease initiation. Our results establish a non-redundant function of slc15a4 in regulating both innate and adaptive components of the immune response in SLE pathobiology and suggest that it may be an attractive drug target.

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

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
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).

scholarly journals B Cells in Autoimmune Diseases

Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
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.

HLAs in Autoimmune Diseases: Dependable Diagnostic Biomarkers?

2019 ◽  
Vol 15 (4) ◽  
pp. 269-276 ◽  
Author(s):  
Elham Rajaei ◽  
Mohammad Taha Jalali ◽  
Saeid Shahrabi ◽  
Ali Amin Asnafi ◽  
Seyed Mohammad Sadegh Pezeshki
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Type 1 Diabetes ◽  
Autoimmune Diseases ◽  
Antigen Presentation ◽  
Lupus Erythematosus ◽  
Human Leukocyte ◽  
Systemic Lupus ◽  
Hla Alleles ◽  
Behcet’S Syndrome

Background: The process of antigen presentation to immune cells is an undeniable contributor to the pathogenesis of autoimmune diseases. Different studies have indicated several factors that are related to autoimmunity. Human Leukocyte Antigens (HLAs) are among such factors, which have a key role in autoimmunity because of their involvement in antigen presentation process. Methods: Relevant English language literature was searched and retrieved from Google Scholar search engine and PubMed database (1996-2018). The following keywords were used: "Human leukocyte antigen", "Behcet’s syndrome", "Rheumatoid arthritis", "Systemic lupus erythematosus", "Type 1 diabetes", "Celiac Disease" and "Autoimmunity". Results: There is a strong association between HLA alleles and autoimmune diseases. For instance, HLA-B alleles and Behcet’s syndrome are strongly correlated, and systemic lupus erythematosus and Type 1 diabetes are related to HLA-DQA1 and HLA-DQB1, respectively. Conclusion: Association between numerous HLA alleles and autoimmune diseases may justify and rationalize their use as biomarkers as well as possible diagnostic laboratory parameters.

scholarly journals AB0123 CHANGES IN CELLULAR GLYCOSYLATION AS A KEY FACTOR IN THE IMMUNOPATHOGENESIS OF SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1361.1-1362
Author(s):  
I. Alves ◽  
V. Pinto ◽  
B. Santos-Pereira ◽  
A. Campar ◽  
J. R. Vizcaino ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Lupus Nephritis ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Protein Glycosylation ◽  
Systemic Lupus ◽  
Specific Mechanism

Background:Systemic Lupus Erythematous (SLE) is one of the most challenging autoimmune diseases as it may be presented as a severe, relapsing and disabling immune-mediated disorder still remaining incurable (1,2).Protein glycosylation is an essential post translational modification that participate in the correct recognition of cells by the immune system (3–5). Moreover, glycosylation changes in T cells (specifically loss of branchedN-glycans mediated by GnTV, encoded byMGAT5gene) have been shown to impact its intrinsic function and activity in a diverse panel of autoimmune diseases (3,4,6)Objectives:To evaluate the impact of glycans in the cellular and molecular mechanisms underlying the loss of immune-tolerance, envisioning the identification of a new targeted-specific mechanism.Methods:We have analysed the profile of cellular glycosylation of a subset of biopsy-proven lupus nephritis from SLE patients and normal kidney tissue (from two Porto Centre Hospitals), through immunohistochemistry (IHC) as well as by real time PCR using RNA extracted from paraffin tissues. Blood samples were collected and were analysed by flow cytometry.Mgat5null mice with 15-months old were monitored for autoimmune signs by evaluating proteinuria, weight loss and colon and kidney tissues were analysed by IHC and FACS.Results:SLE patients revealed a significant decreased expression of complexN-glycans in the renal parenchyma, when compared to healthy kidney. In addition, we have identified in lupus nephritis patients a unique subset of circulatory CD3+T cells with an abnormal glycosignature and displaying an increased expression of specific glycan-binding receptors. Interestingly,Mgat5null mice develop clinical signs compatible within autoimmune-like syndrome together with an increased infiltration of specific CD3+T cells subset identified in SLE patients.Conclusion:These findings point towards the identification of a novel immune player with increased ability to sense abnormalN-glycans, modulating the surrounding immune response. We propose glycosylation as a regulatory mechanism that tips the balance between homeostasis/self-tolerance and autoimmunity opening a potential novel targeted-specific mechanism in SLE pathogenesis.References:[1]Tsokos GC et al. New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol. 2016 Nov 22;12(12):716–30.[2]Marinho A et al. Vitamin D supplementation effects on FoxP3 expression in T cells and FoxP3+/IL-17A ratio and clinical course in systemic lupus erythematosus patients: a study in a Portuguese cohort. Immunol Res. 2017 Feb 16;65(1):197–206.[3]Dias AM et al. Metabolic control of T cell immune response through glycans in inflammatory bowel disease. Proc Natl Acad Sci U S A. 2018 May 15;115(20):E4651–60.[4]Pereira MS & Alves I. et al. Glycans as Key Checkpoints of T Cell Activity and Function. Front Immunol. 2018 Nov 27;9:2754.[5]Pinho SS, Reis CA. Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer. 2015 Sep 20;15(9):540–55.[6]Verhelst X et al. Protein Glycosylation as a Diagnostic and Prognostic Marker of Chronic Inflammatory Gastrointestinal and Liver Diseases. Gastroenterology. 2020 Jan 1;158(1):95–110.Acknowledgments:S.S.P. and I.A. acknowledge Group of Studies for Autoimmune diseases (NEDAI) from Portuguese Society of Internal Medicine (SPMI) for Funding and for supporting the attendance at this meeting.Disclosure of Interests:None declared

Screening for Autoimmune Markers Is Unnecessary during Follow-up of Adults with Autoimmune Thrombocytopenic Purpura and no Autoimmune Markers at Onset

2000 ◽  
Vol 83 (01) ◽  
pp. 42-45 ◽  
Author(s):  
J. M. Vantelon ◽  
B. Godeau ◽  
C. André ◽  
P. Bierling
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Antinuclear Antibodies ◽  
Autoimmune Disorders ◽  
Systemic Lupus ◽  
Thrombocytopenic Purpura ◽  
Autoimmune Thrombocytopenic Purpura

SummaryIn an attempt to evaluate the frequency of autoimmune markers in autoimmune thrombocytopenic purpura (AITP) and to determine if autoimmune markers in patients with isolated AITP were associated with particular disease manifestations, we analyzed records of 122 consecutive adults with AITP. Twenty-nine patients (24%) had significant titers of one or several autoimmune markers at AITP onset. Among them, 16 (13%) had antinuclear antibodies. The presence of autoimmune markers did not correlate with presenting feature, response to treatment or long-term outcome of AITP. Six patients (5%) developed seven autoimmune diseases during follow-up, comprising systemic lupus erythematosus, an antiphospholipid syndrome, autoimmune haemolytic anemia (n = 2), Grave’s disease, Hashimoto’s disease and primary biliary cirrhosis. At AITP onset, three of these patients had isolated biological markers of the autoimmune disease they later developed. The annual average incidence rate of autoimmune diseases was 1% per patient-year in the entire group and 0.4% in the group of patients with no autoimmune markers at AITP onset. This low rate is probably due to careful assessment at diagnosis for concomitant overt autoimmune disease. We recommend extensive screening for autoimmune markers at AITP onset, and careful follow-up of patients with autoimmune markers. Routine screening for autoimmune markers during AITP follow-up is not necessary for patients with no autoimmune markers at AITP onset.Systemic lupus erythematosus (SLE) and other autoimmune disorders can complicate autoimmune thrombocytopenic purpura (AITP) or be diagnosed concomitantly with otherwise unremarkable AITP (1, 2). However, the frequency and prognostic value of isolated autoimmune markers (i. e. not associated with an autoimmune disorder), particularly antinuclear antibodies (ANA) at AITP onset or during follow-up is controversial (3-8). For example, the committee organized by George et al. (9) to write guideline on the diagnosis and treatment of AITP stated that the search for ANA and lupus anticoagulant were of “uncertain appropriateness at diagnosis and during follow-up”. In an attempt to help practicians to make decisions, we analyzed the frequency of autoimmune markers and autoimmune disorders at onset and during the follow-up in 122 adults with AITP and no overt autoimmune disease at diagnosis. These consecutive patients were followed by the same physician for a mean period of 6 years, and had routine screening tests for autoimmune markers and disorders at onset, before steroid therapy, and regularly during follow-up.

scholarly journals Rheumatoid arthritis and systemic lupus erythematosus: Pathophysiological mechanisms related to innate immune system

2019 ◽  
Vol 7 ◽  
pp. 205031211987614 ◽  
Author(s):  
Maria Angélica Pabón-Porras ◽  
Sebastian Molina-Ríos ◽  
Jorge Bruce Flórez-Suárez ◽  
Paola Ximena Coral-Alvarado ◽  
Paul Méndez-Patarroyo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Immune Response ◽  
Immune System ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Innate Immune System ◽  
Normal Function ◽  
Innate Immune ◽  
Systemic Lupus

Rheumatoid arthritis and systemic lupus erythematosus are two highly prevalent autoimmune diseases that generate disability and low quality of life. The innate immune system, a long-forgotten issue in autoimmune diseases, is becoming increasingly important and represents a new focus for the treatment of these entities. This review highlights the role that innate immune system plays in the pathophysiology of rheumatoid arthritis and systemic lupus erythematosus. The role of the innate immune system in rheumatoid arthritis and systemic lupus erythematosus pathophysiology is not only important in early stages but is essential to maintain the immune response and to allow disease progression. In rheumatoid arthritis, genetic and environmental factors are involved in the initial stimulation of the innate immune response in which macrophages are the main participants, as well as fibroblast-like synoviocytes. In systemic lupus erythematosus, all the cells contribute to the inflammatory response, but the complement system is the major effector of the inflammatory process. Detecting alterations in the normal function of these cells, besides its contribution to the understanding of the pathophysiology of autoimmune diseases, could help to establish new treatment strategies for these diseases.

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