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 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.

Myocardial Infarction in Systemic Lupus Erythematosus – the Sex Specific Risk Profile

2020 ◽  
Vol 26 ◽  
Author(s):  
Marija Vavlukis ◽  
Daniela Pop-Gjorceva ◽  
Lidija Poposka ◽  
Emilija Sandevska ◽  
Sasko Kedev
Keyword(s):  
Myocardial Infarction ◽  
Systemic Lupus Erythematosus ◽  
Cardiovascular Risk ◽  
Coronary Artery ◽  
Young Women ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Clinical Presentation ◽  
Systemic Lupus ◽  
Antiinflammatory Therapy

Background: Accelerated atherosclerosis is widely present in patients with systemic lupus erythematosus. Objective: The aim of this review is to analyze the relationship between systemic lupus erythematosus and cardiovascular diseases, with the emphasis on acute myocardial infarction. Results: Various molecular mechanisms triggered by infection/inflammation are responsible for endothelial dysfunction and development of atherosclerosis at an earlier age. Contributing factor is the cumulative effect of traditional cardiovascular risk factors interaction with disease related characteristics. Myocardial infarction rates are 2- to 10-fold higher compared to the general population. Young women have the highest relative risk, however, men carry at least 3- fold higher risk than women. Coronary involvement varies from normal coronary artery with thrombosis, coronary microartery vasculitis, coronary arteritis, and coronary atherosclerosis. Typical clinical presentation is observed in men and older women, while atypical is more frequent in young women. Treatment is guided by the underlying mechanism, engaging invasive procedures alone, or accompanied with immunosuppressive and/or antiinflammatory therapy. There are significant gender differences in pathophysiology and clinical presentation. However, they receive the same therapeutic treatments. Conclusion: Systemic lupus erythematosus is a major contributor to atherosclerotic and non-atherosclerotic mechanisms involved in the development of myocardial infarction, which should be taken into account during therapeutic treatment. Although Systemic lupus erythematosus per se is a “female” disease, males are at increased cardiovascular risk and worse outcome. Method: We conducted a literature review through PubMed and Cochrane, using key words: SLE, atherosclerosis, atherothrombosis, coronary artery disease, myocardial infarction, prognosis, sex specifics.

scholarly journals FRI0224 IDENTIFICATION OF RISK AND PROGNOSTIC FACTORS FOR POLYARTERITIS NODOSA PATIENTS WITH DIGITAL GANGRENE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 695.2-695
Author(s):  
D. Xu ◽  
X. Tian ◽  
X. Zeng ◽  
F. Zhang ◽  
L. Zhao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Prognostic Factors ◽  
Retrospective Study ◽  
Polyarteritis Nodosa ◽  
Lupus Erythematosus ◽  
Disease Duration ◽  
Response To Therapy ◽  
Smoking History ◽  
Systemic Lupus ◽  
Poor Outcomes

Background:Polyarteritis nodosa (PAN) is a segmental, necrotizing vascular disease that primarily impacts medium-sized muscle arteries. The estimated annual incidence of PAN is still lacking in China. Digital gangrene is an ischemic manifestation of the limb. However, the causes and the treatment methods vary from case to case, and the outcome is unpredictable. These features emphasize the need to identify measurable variables that accelerate digital gangrene development in PAN patients. However, little effort has been made to identify the clinical and laboratory factors that affect PAN patients with digital gangrene to anticipate their natural history and response to therapy.Objectives:Many patients with polyarteritis nodosa (PAN) complicated with digital gangrene have poor outcomes and related research information is limited. This study was carried out to identify the associated risk and prognostic factors.Methods:We conducted a retrospective study of 148 PAN patients admitted to Peking Union Medical College Hospital (PUMCH) from September 1986 to December 2018. The characteristics, therapeutic regimens, and outcome data for patients with and without gangrene were compared. The Kaplan–Meier method and Cox hazard regression model were used to evaluate the prognostic factors.Results:Forty-seven (31.8%) PAN patients had digital gangrene complications. The average age was 40.4±17.9 years and the average disease duration was 11 (4-27) months. The presence of digital gangrene was correlated with smoking history [odds ratio (OR), 4.27; 95% confidence interval (95% CI), 1.56-11.66] and eosinophil elevation (28.12; 10.30-76.8). Thirty-two (68.1%) gangrene patients received methylprednisolone pulse therapy and all of these patients were treated with cyclophosphamide. Nine patients suffered irreversible organ injury and two died. Disease duration ≥ 24 months and elevated serum C-reactive protein (CRP) were identified as hazardous factors for poor prognosis in patients with gangrene (P=0.003, HR=8.668, 95% CI 2.11, 35.55 andP=0.042, HR=27.062, 95% CI 1.13, 648.57, respectively).Conclusion:Smoking history and eosinophil elevation in PAN patients were more prone to digital gangrene and high serum CRP level predicted poor outcomes. PAN patients with smoking history and elevated eosinophils need to be seriously evaluated by clinicians. Furthermore, the CRP level should be efficiently controlled for good prognosis.References:[1]De Virgilio A, Greco A, Magliulo G, Gallo A, Ruoppolo G, Conte M, et al. Polyarteritis nodosa: A contemporary overview. Autoimmun Rev. 2016;15:564-70.[2]Pagnoux C, Seror R, Henegar C, Mahr A, Cohen P, Le Guern V, et al. Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database. Arthritis Rheum. 2010;62:616-26.[3]Xu D, You X, Wang Z, Zeng Q, Xu J, Jiang L, et al. Chinese Systemic Lupus Erythematosus Treatment and Research Group Registry VI: Effect of Cigarette Smoking on the Clinical Phenotype of Chinese Patients with Systemic Lupus Erythematosus. PLoS One. 2015;10:e0134451.Acknowledgments:NoDisclosure of Interests:Dong Xu: None declared, Xinping Tian: None declared, Xiaofeng Zeng Consultant of: MSD Pharmaceuticals, Fengchun Zhang: None declared, Lin Zhao: None declared, Shangzhu Zhang: None declared, Jiaxin Zhou: None declared, Jiu-liang Zhao: None declared, Xiaodan Kong: None declared

scholarly journals Molecular characteristics of antibodies bearing an anti-DNA-associated idiotype.

1991 ◽  
Vol 174 (6) ◽  
pp. 1639-1652 ◽  
Author(s):  
A Manheimer-Lory ◽  
J B Katz ◽  
M Pillinger ◽  
C Ghossein ◽  
A Smith ◽  
...  
Keyword(s):  
B Cells ◽  
Dna Binding ◽  
Lupus Erythematosus ◽  
Germ Line ◽  
High Titer ◽  
Variable Region ◽  
Amino Acid Sequences ◽  
Molecular Characteristics ◽  
Systemic Lupus ◽  
Dna Antibodies

Anti-double-stranded DNA antibodies are the hallmark of the disease systemic lupus erythematosus and are believed to contribute to pathogenesis. While a large number of anti-DNA antibodies from mice with lupus-like syndromes have been characterized and their variable region genes sequenced, few human anti-DNA antibodies have been reported. We describe here the variable region gene sequences of eight antibodies produced by Epstein-Barr virus (EBV)-transformed B cells that bear the 3I idiotype, an idiotype expressed on anti-DNA antibodies and present in high titer in patients with systemic lupus. The comparison of these antibodies to the light chains of 3I+ myeloma proteins and serum antibodies reveals that EBV transformation yields B cells producing antibodies representative of the expressed antibody repertoire. The analysis of nucleotide and amino acid sequences of these antibodies suggests the first complementarity determining region of the light chain may be important in DNA binding and that paradigms previously generated to account for DNA binding require modification. The understanding of the molecular genetics of the anti-DNA response requires a more complete description of the immunoglobulin germ line repertoire, but data reported here suggest that somatic diversification is a characteristic of the anti-DNA response.

scholarly journals The Impact of T Cell Vaccination in Alleviating and Regulating Systemic Lupus Erythematosus Manifestation

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Liuye Huang ◽  
Yuan Yang ◽  
Yu Kuang ◽  
Dapeng Wei ◽  
Wanyi Li ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Side Effects ◽  
Lupus Erythematosus ◽  
Clinical Symptoms ◽  
Systemic Lupus ◽  
T Cell Vaccination ◽  
Dna Antibodies

Objective. Systemic lupus erythematosus (SLE) is an autoimmune disease identified by a plethora of production of autoantibodies. Autoreactive T cells may play an important role in the process. Attenuated T cell vaccination (TCV) has proven to benefit some autoimmune diseases by deleting or suppressing pathogenic T cells. However, clinical evidence for TCV in SLE is still limited. Therefore, this self-controlled study concentrates on the clinical effects of TCV on SLE patients. Methods. 16 patients were enrolled in the study; they accepted TCV regularly. SLEDAI, clinical symptoms, blood parameters including complements 3 and 4 levels, ANA, and anti-ds-DNA antibodies were tested. In addition, the side effects and drug usage were observed during the patients’ treatment and follow-up. Results. Remissions in clinical symptoms such as facial rash, vasculitis, and proteinuria were noted in most patients. There are also evident reductions in SLEDAI, anti-ds-DNA antibodies, and GC dose and increases in C3 and C4 levels, with no pathogenic side effects during treatment and follow-up. Conclusions. T cell vaccination is helpful in alleviating and regulating systemic lupus erythematosus manifestation.

scholarly journals An Early Unexpected Immune Thrombotic Thrombocytopenic Purpura Relapse Associated with SARS-CoV-2 Infection: A Case Report and Literature Review

2021 ◽  
pp. 1-5
Author(s):  
Maya Kornowski Cohen ◽  
Liron Sheena ◽  
Yair Shafir ◽  
Vered Yahalom ◽  
Anat Gafter-Gvili ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Case Report ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Lupus Erythematosus ◽  
Response To Therapy ◽  
Intravascular Hemolysis ◽  
Systemic Lupus ◽  
Thrombocytopenic Purpura ◽  
History Of ◽  
Triggering Factor

SARS-CoV-2 has been reported as a possible triggering factor for the development of several autoimmune diseases and inflammatory dysregulation. Here, we present a case report of a woman with a history of systemic lupus erythematosus and antiphospholipid syndrome, presenting with concurrent COVID-19 infection and immune thrombotic thrombocytopenic purpura (TTP). The patient was treated with plasma exchange, steroids, and caplacizumab with initial good response to therapy. The course of both TTP and COVID-19 disease was mild. However, after ADAMTS-13 activity was normalized, the patient experienced an early unexpected TTP relapse manifested by intravascular hemolysis with stable platelet counts requiring further treatment. Only 3 cases of COVID-19 associated TTP were reported in the literature thus far. We summarize the literature and suggest that COVID-19 could act as a trigger for TTP, with good outcomes if recognized and treated early.

scholarly journals Is systemic lupus erythematosus different in urban versus rural living environment? Data from the Cretan Lupus Epidemiology and Surveillance Registry

Lupus ◽  
2018 ◽  
Vol 28 (1) ◽  
pp. 104-113 ◽  
Author(s):  
I Gergianaki ◽  
A Fanouriakis ◽  
C Adamichou ◽  
G Spyrou ◽  
N Mihalopoulos ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Disease Diagnosis ◽  
Living Environment ◽  
Rural Residence ◽  
Systemic Lupus ◽  
Rural Living ◽  
Urban Rural ◽  
Rural Patients ◽  
Urban Versus

Background Examining urban–rural differences can provide insights into susceptibility or modifying factors of complex diseases, yet limited data exist on systemic lupus erythematosus (SLE). Objective To study SLE risk, manifestations and severity in relation to urban versus rural residence. Methodology Cross-sectional analysis of the Crete Lupus Registry. Demographics, residency history and clinical data were obtained from interviews and medical records ( N=399 patients). Patients with exclusively urban, rural or mixed urban/rural residence up to enrolment were compared. Results The risk of SLE in urban versus rural areas was 2.08 (95% confidence interval: 1.66–2.61). Compared with rural, urban residence was associated with earlier (by almost seven years) disease diagnosis – despite comparable diagnostic delay – and lower female predominance (6.8:1 versus 15:1). Rural patients had fewer years of education and lower employment rates. Smoking was more frequent among urban, whereas pesticide use was increased among rural patients. A pattern of malar rash, photosensitivity, oral ulcers and arthritis was more prevalent in rural patients. Residence was not associated with organ damage although moderate/severe disease occurred more frequently among rural-living patients (multivariable adjusted odds ratio: 2.17, p=0.011). Conclusion Our data suggest that the living environment may influence the risk, gender bias and phenotype of SLE, not fully accounted for by sociodemographic factors.

scholarly journals Neutrophil Extracellular Traps-DNase Balance and Autoimmunity

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2667
Author(s):  
Andrea Angeletti ◽  
Stefano Volpi ◽  
Maurizio Bruschi ◽  
Francesca Lugani ◽  
Augusto Vaglio ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Causative Factor ◽  
Neutrophil Extracellular Traps ◽  
Limiting Factor ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Number Of Patients ◽  
Selective Depletion ◽  
Dna Antibodies ◽  
Rate Limiting

Neutrophil extracellular traps (NETs) are macromolecular structures programmed to trap circulating bacteria and viruses. The accumulation of NETs in the circulation correlates with the formation of anti-double-stranded (ds) DNA antibodies and is considered a causative factor for systemic lupus erythematosus (SLE). The digestion of DNA by DNase1 and DNases1L3 is the rate- limiting factor for NET accumulation. Mutations occurring in one of these two DNASE genes determine anti-DNA formation and are associated with severe Lupus-like syndromes and lupus nephritis (LN). A second mechanism that may lead to DNase functional impairment is the presence of circulating DNase inhibitors in patients with low DNase activity, or the generation of anti-DNase antibodies. This phenomenon has been described in a relevant number of patients with SLE and may represent an important mechanism determining autoimmunity flares. On the basis of the reviewed studies, it is tempting to suppose that the blockade or selective depletion of anti-DNase autoantibodies could represent a potential novel therapeutic approach to prevent or halt SLE and LN. In general, strategies aimed at reducing NET formation might have a similar impact on the progression of SLE and LN.

scholarly journals Estrogen Receptor Signaling and Its Relationship to Cytokines in Systemic Lupus Erythematosus

2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
E. Kassi ◽  
P. Moutsatsou
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Estrogen Receptor ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Cytokine Production ◽  
Receptor Protein ◽  
Receptor Subtypes ◽  
Receptor Signaling ◽  
Systemic Lupus ◽  
Estrogen Receptor Signaling

Dysregulation of cytokines is among the main abnormalities in Systemic Lupus Erythematosus (SLE). However, although, estrogens, which are known to be involved in lupus disease, influence cytokine production, the underlying molecular mechanisms remain poorly defined. Recent evidence demonstrates the presence of estrogen receptor in various cell types of the immune system, while divergent effects of estrogens on the cytokine regulation are thought to be implicated. In this paper, we provide an overview of the current knowledge as to how estrogen-induced modulation of cytokine production in SLE is mediated by the estrogen receptor while simultaneously clarifying various aspects of estrogen receptor signaling in this disease. The estrogen receptor subtypes, their structure, and the mode of action of estrogens by gene activation and via extranuclear effects are briefly presented. Results regarding the possible correlation between estrogen receptor gene polymorphisms and quantitative changes in the receptor protein to SLE pathology and cytokine production are reviewed.

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