scholarly journals A mikro-RNS-ek jelentősége szisztémás autoimmun betegségek kialakulásában

2019 ◽  
Vol 160 (15) ◽  
pp. 563-572 ◽  
Author(s):  
Ilona Jámbor ◽  
Krisztina Szabó ◽  
Margit Zeher ◽  
Gábor Papp
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Immune Cell ◽  
Cell Lineage ◽  
Therapeutic Approaches ◽  
Systemic Autoimmune Diseases ◽  
Protein Coding ◽  
Diagnosis And Prognosis ◽  
Research Findings ◽  
Posttranscriptional Level

Abstract: MicroRNAs (miRNAs) are 18–25 nucleotide long, single stranded, endogenous, non-coding small RNAs playing an important role in regulating gene expression at posttranscriptional level. miRNAs control approximately 90% of protein-coding genes, and play a central role in various biological processes including immune cell lineage commitment, differentiation, proliferation, apoptosis and maintenance of immune homeostasis. Changes in the expression of certain miRNAs may lead to the development of many diseases, including systemic autoimmune diseases. In this study, we summarize the biogenesis of miRNAs, their role in regulation of the immune system, and review the latest research findings in systemic lupus erythematosus, primary Sjögren’s syndrome, rheumatoid arthritis and systemic sclerosis. In the future, miRNAs may help not only in establishing diagnosis and prognosis but potentially serve as targets for modern therapeutic approaches in autoimmune diseases. Orv Hetil. 2019; 160(15): 563–572.

scholarly journals DNA Damage Response and Oxidative Stress in Systemic Autoimmunity

2019 ◽  
Vol 21 (1) ◽  
pp. 55 ◽  
Author(s):  
Vassilis L. Souliotis ◽  
Nikolaos I. Vlachogiannis ◽  
Maria Pappa ◽  
Alexandra Argyriou ◽  
Panagiotis A. Ntouros ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Dna Damage ◽  
Autoimmune Diseases ◽  
Dna Damage Response ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Tissue Injury ◽  
Systemic Autoimmune Diseases ◽  
Damage Response

The DNA damage response and repair (DDR/R) network, a sum of hierarchically structured signaling pathways that recognize and repair DNA damage, and the immune response to endogenous and/or exogenous threats, act synergistically to enhance cellular defense. On the other hand, a deregulated interplay between these systems underlines inflammatory diseases including malignancies and chronic systemic autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Patients with these diseases are characterized by aberrant immune response to self-antigens with widespread production of autoantibodies and multiple-tissue injury, as well as by the presence of increased oxidative stress. Recent data demonstrate accumulation of endogenous DNA damage in peripheral blood mononuclear cells from these patients, which is related to (a) augmented DNA damage formation, at least partly due to the induction of oxidative stress, and (b) epigenetically regulated functional abnormalities of fundamental DNA repair mechanisms. Because endogenous DNA damage accumulation has serious consequences for cellular health, including genomic instability and enhancement of an aberrant immune response, these results can be exploited for understanding pathogenesis and progression of systemic autoimmune diseases, as well as for the development of new treatments.

scholarly journals Tocilizumab for the Treatment of Rheumatoid Arthritis and Other Systemic Autoimmune Diseases: Current Perspectives and Future Directions

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Atsushi Ogata ◽  
Toshio Tanaka
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
Host Defense ◽  
Lupus Erythematosus ◽  
Therapeutic Strategy ◽  
Case Reports ◽  
Systemic Autoimmune Diseases ◽  
Future Directions ◽  
Pilot Studies ◽  
Beneficial Effects

Interleukin (IL)-6 is a cytokine featuring redundancy and pleiotropic activity. While IL-6, when transiently produced, contributes to host defense against acute environmental stress, continuous dysregulated IL-6 production plays a significant pathological role in several systemic autoimmune diseases. In response to the expectation that IL-6 blockade would constitute a novel therapeutic strategy for the treatment of these diseases, tocilizumab, a humanized anti-IL-6 receptor antibody, was developed. Clinical trials have verified the efficacy and the safety of tocilizumab for patients with rheumatoid arthritis, resulting in approval of this innovative biologic for the treatment of rheumatoid arthritis in more than 90 countries worldwide. Pathological analyses of the effect of IL-6 on the development of autoimmune diseases and a considerable number of case reports and pilot studies have also indicated the beneficial effects of this antibody on other systemic autoimmune diseases, including systemic lupus erythematosus, systemic sclerosis, polymyositis, and large-vessel vasculitis.

scholarly journals Identification of a Shared Microbiomic and Metabolomic Profile in Systemic Autoimmune Diseases

2019 ◽  
Vol 8 (9) ◽  
pp. 1291 ◽  
Author(s):  
Bellocchi ◽  
Fernández-Ochoa ◽  
Montanelli ◽  
Vigone ◽  
Santaniello ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
High Performance ◽  
16S Rrna Gene Sequencing ◽  
Study Groups ◽  
Mass Spectrometry Analysis ◽  
Rrna Gene ◽  
Operating Characteristics ◽  
Systemic Autoimmune Diseases ◽  
Spectrometry Analysis

Dysbiosis has been described in systemic autoimmune diseases (SADs), including systemic lupus erythematosus (SLE), Sjögren’s syndrome (SjS), and primary anti-phosholipid syndrome (PAPS), however the biological implications of these associations are often elusive. Stool and plasma samples from 114 subjects, including in SLE (n = 27), SjS (n = 23), PAPs (n = 11) and undifferentiated connective tissue (UCTD, n = 26) patients, and geographically-matched healthy controls (HCs, n = 27), were collected for microbiome (16s rRNA gene sequencing) and metabolome (high-performance liquid chromatography coupled to mass spectrometry) analysis to identify shared characteristics across diseases. Out of 130 identified microbial genera, a subset of 29 bacteria was able to differentiate study groups (area under receiver operating characteristics (AUROC) = 0.730 ± 0.025). A fair classification was obtained with a subset of 41 metabolic peaks out of 254 (AUROC = 0.748 ± 0.021). In both models, HCs were well separated from SADs, while UCTD largely overlapped with the other diseases. In all of the SADs pro-tolerogenic bacteria were reduced, while pathobiont genera were increased. Metabolic alterations included two clusters comprised of: (a) members of the acylcarnitine family, positively correlating with a Prevotella-enriched cluster and negatively correlating with a butyrate-producing bacteria-enriched cluster; and (b) phospholipids, negatively correlating with butyrate-producing bacteria. These findings demonstrate a strong interaction between intestinal microbiota and metabolic function in patients with SADs.

scholarly journals Occurrence and Antigenic Specificity of Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (P-ANCA) in Systemic Autoimmune Diseases

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2128
Author(s):  
Ourania D. Argyropoulou ◽  
Andreas V. Goules ◽  
Georgios Boutzios ◽  
Alexandra Tsirogianni ◽  
Charalampos Sfontouris ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Staining Pattern ◽  
The Other ◽  
Cathepsin G ◽  
Antigenic Specificity ◽  
Positive Staining ◽  
Systemic Lupus ◽  
Systemic Autoimmune Diseases ◽  
Autoimmune Rheumatic Diseases

Perinuclear anti-neutrophilic cytoplasmic antibodies (P-ANCA) recognize heterogeneous antigens, including myeloperoxidase (MPO), lactoferrin, elastase, cathepsin-G and bactericidal/permeability-increasing protein. Although P-ANCA have diagnostic utility in vasculitides, they may also be found in patients with various other systemic autoimmune rheumatic diseases (SARDs). Nevertheless, the clinical significance and the targets recognized by P-ANCA in such patients remain unclear. For this purpose, herein we investigated the occurrence of ANCA-related antigenic specificities in 82 P-ANCA-positive sera by multiplex ELISA, as well as their association with other autoantibodies. The P-ANCA-positive sera corresponded to patients with vasculitides (n = 24), systemic lupus erythematosus (n = 28), antiphospholipid syndrome (n = 5), Sjögren’s syndrome (n = 7), rheumatoid arthritis (n = 3), systemic scleroderma (n = 1), sarcoidosis (n = 1) and Hashimoto′s thyroiditis (n = 13). In most P-ANCA-positive patients studied (51/82, 62.3%), these autoantibodies occurred in high titers (>1:160). The analysis of P-ANCA-positive sera revealed reactivity to MPO in only 50% of patients with vasculitides, whereas it was infrequent in the other disease groups studied. Reactivity to other P-ANCA-related autoantigens was also rarely detected. Our findings support that high P-ANCA titers occur in SARD. The P-ANCA-positive staining pattern is associated with MPO specificity in vasculitides, while in other autoimmune diseases, it mostly involves unknown autoantigens.

scholarly journals Phage display identification of immunodominant epitopes and autoantibodies in autoimmune diseases

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Marco Palma
Keyword(s):  
Autoimmune Diseases ◽  
Phage Display ◽  
Lupus Erythematosus ◽  
Clinical Signs ◽  
Immunosuppressive Drugs ◽  
Antigenic Structure ◽  
Therapeutic Approaches ◽  
Invaluable Tool ◽  
Epitope Sharing ◽  
Immunodominant Epitopes

Phage display represents an invaluable tool to study autoimmune diseases. The side effects of immunosuppressive drugs for the treatment of autoimmune diseases raise awareness of the need to explore alternative therapeutic approaches such as antibodies and peptides. Therefore, phage display is an important technique for generating such molecules, so the purpose of this review is to determine the potential advantages of this technique in the research of autoimmune diseases. Many studies have also demonstrated the efficacy of phage display in identifying immunodominant epitopes of autoimmune diseases such as Goodpasture disease, immunologic thrombocytopenia, and systemic lupus erythematosus. Phage display peptide libraries have been screened with immunopurified autoantibodies from patients with autoimmune diseases. This makes it possible to more precisely locate the autoantibody binding sites, reveal a possible epitope sharing between the host and microbe, and identify a motif that mimics an antigenic structure such as that of dsDNA. Several studies have been conducted that have investigated the effectiveness of phage display in isolating autoantibody repertoires of autoantibodies against human epitopes. This allows the identification and design of antibody fragments (e.g., Fab, scFv, sdAb) that could block the binding of autoantibodies such as the deposition of IgG in the kidney and reduce the clinical signs of disease. In conclusion, phage display helps identify common epitopes and hotspot residues that can be potential therapeutic targets for the treatment of autoimmune diseases. This leads to a better understanding of the immunopathogenesis of autoimmune diseases and the development of more specific therapeutic strategies.

Therapeutic potential of galectin-1 and galectin-3 in autoimmune diseases

2021 ◽  
Vol 27 ◽  
Author(s):  
Yi-Sheng He ◽  
Yu-Qian Hu ◽  
Kun Xiang ◽  
Yue Chen ◽  
Ya-Ting Feng ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Cell Activity ◽  
Vital Role ◽  
Promising Therapeutic Target ◽  
Galectin 3

: Galectins are a highly conserved protein family that binds to β-galactosides. Different members of this family play a variety of biological functions in physiological and pathological processes such as angiogenesis, regulation of immune cell activity, and cell adhesion. Galectins are widely distributed and play a vital role both inside and outside cells. It can regulate homeostasis and immune function in vivo through mechanisms such as apoptosis. Recent studies indicate that galectins exhibit pleiotropic roles in inflammation. Furthermore, emerging studies have found that galectins are involved in the occurrence and development of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D) and systemic sclerosis (SSc) by regulating cell adhesion, apoptosis, and other mechanisms. This review will briefly discuss the biological characteristics of the two most widely expressed and extensively explored members of the galectin family, galectin-1 and galectin-3, as well as their pathogenetic and therapeutic roles in autoimmune diseases. These information may provide a novel and promising therapeutic target for autoimmune diseases.

scholarly journals Tertiary lymphoid organs in systemic autoimmune diseases:  pathogenic or protective?

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 196 ◽  
Author(s):  
William D. Shipman ◽  
Dragos C. Dasoveanu ◽  
Theresa T. Lu
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Lymphoid Organs ◽  
T And B Cells ◽  
Systemic Lupus ◽  
Disease Pathogenesis ◽  
Systemic Autoimmune Diseases ◽  
Effector Cells ◽  
Secondary Lymphoid Organs

Tertiary lymphoid organs are found at sites of chronic inflammation in autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. These organized accumulations of T and B cells resemble secondary lymphoid organs and generate autoreactive effector cells. However, whether they contribute to disease pathogenesis or have protective functions is unclear. Here, we discuss how tertiary lymphoid organs can generate potentially pathogenic cells but may also limit the extent of the response and damage in autoimmune disease.

scholarly journals Epstein-Barr Virus in Systemic Autoimmune Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Anette Holck Draborg ◽  
Karen Duus ◽  
Gunnar Houen
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Epstein Barr Virus ◽  
Immune Escape ◽  
Connective Tissue Diseases ◽  
Systemic Autoimmune Diseases ◽  
Barr Virus ◽  
Epstein Barr ◽  
Genetic And Environmental Factors ◽  
Immune Escape Mechanisms

Systemic autoimmune diseases (SADs) are a group of connective tissue diseases with diverse, yet overlapping, symptoms and autoantibody development. The etiology behind SADs is not fully elucidated, but a number of genetic and environmental factors are known to influence the incidence of SADs. Recent findings link dysregulation of Epstein-Barr virus (EBV) with SAD development. EBV causes a persistent infection with a tight latency programme in memory B-cells, which enables evasion of the immune defence. A number of immune escape mechanisms and immune-modulating proteins have been described for EBV. These immune modulating functions make EBV a good candidate for initiation of autoimmune diseases and exacerbation of disease progression. This review focuses on systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren’s syndrome (SS) and sum up the existing data linking EBV with these diseases including elevated titres of EBV antibodies, reduced T-cell defence against EBV, and elevated EBV viral load. Together, these data suggest that uncontrolled EBV infection can develop diverse autoreactivities in genetic susceptible individuals with different manifestations depending on the genetic background and the site of reactivation.

scholarly journals AB1051 KIKUCHI FUJIMOTO DISEASE, IS IT SLE?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1815.3-1816
Author(s):  
J. Camins-Fàbregas ◽  
V. Ortiz-Santamaria ◽  
N. Busquets-Pérez ◽  
A. Cuervo ◽  
I. Cañas Alcántara ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Response To Treatment ◽  
Systemic Autoimmune Disease ◽  
Histiocytic Necrotizing Lymphadenitis ◽  
Systemic Autoimmune Diseases ◽  
Necrotizing Lymphadenitis

Background:Kikuchi-Fujimoto disease (KFD) is a rare entity characterized by adenopathies and fever. It raises a broad differential diagnosis that includes lymphoproliferative disorders, infections and systemic autoimmune diseases, and diagnostic confirmation is always by histology, which shows histiocytic necrotizing lymphadenitis. Although its course is generally benign and self-limited, it can be associated both at the time of diagnosis and during follow-up with systemic autoimmune diseases, the most frequent of which is systemic lupus erythematosus (SLE).Objectives:To describre the clinical and analytical characteristics of patients diagnosed with KFD and the development of systemic autoimmune disease.Methods:Patients diagnosed with KFD during the 1990s and 2020s are collected in a regional hospital (Granollers General Hospital). The clinic is documented at the diagnosis of EKF, the appearance of systemic autoimmune disease during follow-up and its clinical and analytical characteristics.Results:A total of 7 patients with EKF were diagnosed. All of them women with a mean age at diagnosis of 30 years. Diagnosis was made in all cases with compatible clinical symptoms, fever and lymphadenopathy, and lymph node biopsy confirming histiocytic necrotizing lymphadenitis. At the time of diagnosis, a patient was also diagnosed with SLE. During the follow-up, 4 of the 6 remaining patients developed clinical manifestations compatible with SLE (3 of them with systemic manifestations and a case of subacute cutaneous lupus. The mean time of onset of SLE was 34 months (between 6 months and 5 years). All of them received treatment with hydroxychloroquine, with good response to treatment.The clinical and analytical characteristics are presented in Table 1 below.Conclusion:In our center, 5 of the 7 patients (71%) diagnosed with EKF developed manifestations compatible with SLE. The importance of the diagnosis of EKF lies precisely in the possible association with systemic autoimmune disease, the most common being SLE, so it is recommended that patients be monitored to identify those who develop associated autoimmune disease.Disclosure of Interests:None declared

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