scholarly journals Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease

2020 ◽  
Author(s):  
Irina A Pashnina ◽  
Irina M Krivolapova ◽  
Tamara V Fedotkina ◽  
Varvara A Ryabkova ◽  
Margarita V Chereshneva ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Young People ◽  
Autoimmune Diseases ◽  
Antinuclear Antibodies ◽  
Normal Range ◽  
Cell Functions ◽  
Low Concentrations ◽  
Antinuclear Autoantibodies ◽  
Underlying Causes

Incidence of autoimmune diseases increases. Antinuclear antibodies (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in health increased over last decades, especially among young people. ANA in health occur in low concentrations, with prevalence up to 50% in some populations, which demands a cutoff revision. The review deals with origin and probable physiological or compensatory function of ANA in health, according to the concept of immunological clearance, theory of autoimmune regulation of cell functions and the concept of functional autoantibodies. Considering ANA titers ≤1:320 as a serological marker of autoimmune diseases seems inappropriate. The role of anti-DFS70/LEDGFp75 autoantibodies is highlighted as possible anti-risk biomarker for autoimmune rheumatic disorders. ANA prevalence in health is different in various regions due to several underlying causes discussed in the review, all influencing in additive combinations according to the concept of the mosaic of autoimmunity. Not only titer, but the HEp-2 IFA staining patterns, like AC-2, is also important. Accepting autoantibodies as a kind of bioregulators, not only upper, but also lower borders of their normal range should be determined. Not only their excess, but also lack of them or “autoimmunodeficiency” could be a reason of disorders.

scholarly journals Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease

Antibodies ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 9
Author(s):  
Irina A. Pashnina ◽  
Irina M. Krivolapova ◽  
Tamara V. Fedotkina ◽  
Varvara A. Ryabkova ◽  
Margarita V. Chereshneva ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Antinuclear Antibody ◽  
Normal Range ◽  
Cell Functions ◽  
Low Concentrations ◽  
Antinuclear Autoantibodies ◽  
Underlying Causes ◽  
Healthy Persons

The incidence of autoimmune diseases is increasing. Antinuclear antibody (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in healthy persons has increased over the last decades, especially among young people. ANA in health occurs in low concentrations, with a prevalence up to 50% in some populations, which demands a cutoff revision. This review deals with the origin and probable physiological or compensatory function of ANA in health, according to the concept of immunological clearance, theory of autoimmune regulation of cell functions, and the concept of functional autoantibodies. Considering ANA titers ≤1:320 as a serological marker of autoimmune diseases seems inappropriate. The role of anti-DFS70/LEDGFp75 autoantibodies is highlighted as a possible anti-risk biomarker for autoimmune rheumatic disorders. ANA prevalence in health is different in various regions due to several underlying causes discussed in the review, all influencing additive combinations according to the concept of the mosaic of autoimmunity. Not only are titers, but also HEp-2 IFA) staining patterns, such as AC-2, important. Accepting autoantibodies as a kind of bioregulator, not only the upper, but also the lower borders of their normal range should be determined; not only their excess, but also a lack of them or “autoimmunodeficiency” could be the reason for disorders.

Predictive autoimmunity using autoantibodies: screening for anti-nuclear antibodies

2018 ◽  
Vol 56 (10) ◽  
pp. 1771-1777 ◽  
Author(s):  
Dolores Pérez ◽  
Boris Gilburd ◽  
Óscar Cabrera-Marante ◽  
Jose A. Martínez-Flores ◽  
Manuel Serrano ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Early Detection ◽  
Autoimmune Diseases ◽  
Antinuclear Antibodies ◽  
Standard Technique ◽  
Clinical Suspicion ◽  
Follow Up Study ◽  
Asymptomatic Subjects

Abstract Background: Early detection of antinuclear antibodies (ANA) in asymptomatic subjects is useful to predict autoimmune diseases years before diagnosis. ANA have been determined by indirect immunofluorescence (IIF) using human epithelial type 2 (HEp-2) cells, which is considered the gold standard technique. Multiplex technology (BioPlex ANA Screen) has been introduced for ANA evaluation in recent years. Nevertheless, concordance between BioPlex and IIF is low and there is no harmonization between both methods for detection of autoantibodies. This study has aimed to clarify the clinical significance of autoantibodies detected by BioPlex ANA Screen in subjects with undiagnosed clinical suspicion of autoimmune disease and to determine the predictive value of autoantibodies detected by BioPlex ANA Screen. Methods: A 3-year follow-up study was performed of 411 subjects without a clear diagnosis of autoimmune diseases in whom autoantibodies were detected by BioPlex ANA Screen that were negative by IIF on HEp-2 cells. Results: At 3 years of follow-up, 312 (76%) subjects were positive for autoantibodies by IIF and 99 subjects continued to be negative. A diagnosis of autoimmune disease was found in most of the subjects (87%). Conclusions: BioPlex ANA Screen has greater sensitivity than IIF on HEp-2 cells for autoantibodies detection. Early detection of these antibodies by BioPlex can predict possible development of autoimmune diseases.

scholarly journals Role of the Lipoperoxidation Product 4-Hydroxynonenal in the Pathogenesis of Severe Malaria Anemia and Malaria Immunodepression

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Evelin Schwarzer ◽  
Paolo Arese ◽  
Oleksii A. Skorokhod
Keyword(s):  
Oxidative Stress ◽  
Severe Malaria ◽  
Chemical Properties ◽  
Oxidative Stress Marker ◽  
Pathogenic Factor ◽  
Biologically Relevant ◽  
Cell Functions ◽  
Low Concentrations ◽  
Covalent Conjugates

Oxidative stress plays an important role in the pathogenesis offalciparummalaria, a disease still claiming close to 1 million deaths and 200 million new cases per year. Most frequent complications are severe anemia, cerebral malaria, and immunodepression, the latter being constantly present in all forms of malaria. Complications are associated with oxidative stress and lipoperoxidation. Its final product 4-hydroxynonenal (4-HNE), a stable yet very reactive and diffusible molecule, forms covalent conjugates with proteins, DNA, and phospholipids and modulates important cell functions at very low concentrations. Since oxidative stress plays important roles in the pathogenesis of severe malaria, it appears important to explore the role of 4-HNE in two important malaria complications such as malaria anemia and malaria immunodepression where oxidative stress is considered to be involved. In this review we will summarize data about 4-HNE chemistry, its biologically relevant chemical properties, and its role as regulator of physiologic processes and as pathogenic factor. We will review studies documenting the role of 4-HNE in severe malaria with emphasis on malaria anemia and immunodepression. Data from other diseases qualify 4-HNE both as oxidative stress marker and as pathomechanistically important molecule. Further studies are needed to establish 4-HNE as accepted pathogenic factor in severe malaria.

scholarly journals Antinuclear Antibodies: Marker of Diagnosis and Evolution in Autoimmune Diseases

2018 ◽  
Vol 49 (3) ◽  
pp. e62-e73 ◽  
Author(s):  
Lucia M Sur ◽  
Emanuela Floca ◽  
Daniel G Sur ◽  
Marius C Colceriu ◽  
Gabriel Samasca ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Antinuclear Antibodies ◽  
Test Results ◽  
Correct Interpretation ◽  
Healthy Individuals ◽  
A Cell ◽  
Specific Antigens ◽  
Blood Specimens ◽  
Human Laryngeal Carcinoma

Abstract Antinuclear antibodies (ANAs) are autoantibodies that attack self-proteins within cell nucleus structures; their presence in serum may indicate an autoimmune disease. Also, positive ANA test results have been obtained in chronic infectious diseases, cancers, medication-related adverse events, and even healthy individuals. As a result, a correct interpretation of the presence of ANAs is needed. Identification of ANAs subtypes is an important part of clinical immunology. The presence of ANAs in patient blood specimens is detected using a cell-line substrate from human laryngeal carcinoma (HEp-2 cells). On this substrate, ANAs will bind specific antigens, which will lead to a suggestive fluorescent emission. The fluorescence patterns visualized under the fluorescence microscope can be correlated with certain subtypes of ANA and certain autoimmune diseases. Depending on the subtype of ANA present in the serum and the targeted antigen, several staining patterns are reported, namely, nuclear patterns, nucleolar patterns, cell cycle patterns, or cytoplasmatic patterns. Identification of a certain pattern can lead to diagnosis of a certain autoimmune disease.

scholarly journals THE ASSOCIATION OF CELIAC DISEASE WITH OTHER AUTOIMMUNE DISEASES IN CHILDREN

2017 ◽  
pp. 023
Author(s):  
Jelisaveta Maksimović ◽  
Zlatko Djurić
Keyword(s):  
Celiac Disease ◽  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Clinical Signs ◽  
Protective Role ◽  
North American Population ◽  
Gluten Free ◽  
American Population ◽  
Gastrointestinal Manifestations

Celiac disease (CD) is an autoimmune disease with estimated prevalence of 1% in European and North American population. All four components of CD autoimmunity are well known, such as: genetics, autoantigen, autoantibodies and the environmental triggers. Besides gastrointestinal manifestations, celiac disease has a wide array of extraintestinal symptoms and clinical signs. This article briefly summarizes celiac disease pathophysiology and association of celiac disease with other autoimmune diseases in children. It puts emphasis on possible protective role of gluten-free diet for the development of other autoimmune diseases in patients with celiac disease.

scholarly journals Evidence for a potential role of miR-1908-5p and miR-3614-5p in autoimmune disease risk using genome-wide analyses

2018 ◽  
Author(s):  
Inken Wohlers ◽  
Lars Bertram ◽  
Christina M. Lill
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Disease Risk ◽  
Association Studies ◽  
Microrna Expression ◽  
Next Generation Sequencing Data ◽  
Genome Wide Association Studies ◽  
Functional Variants ◽  
Genome Wide

AbstractGenome-wide association studies (GWAS) have identified a large number of genetic risk loci for autoimmune diseases. However, the functional variants underlying these disease associations remain largely unknown. There is evidence that microRNA-mediated regulation may play an important role in this context. Therefore, we assessed whether autoimmune disease loci unfold their effects via altering microRNA expression in relevant immune cells.To this end, we performed microRNA expression quantitative trait loci (eQTL) analyses across 115 GWAS regions associated with 12 autoimmune diseases using next-generation sequencing data of 345 lymphoblastoid cell lines. Statistical analyses included the application and extension of a recently proposed framework (joint likelihood mapping), to microRNA expression data and microRNA target gene enrichment analyses of relevant GWAS data.Overall, only a minority of autoimmune disease risk loci may exert their pathophysiologic effects by altering miRNA expression based on JLIM. However, detailed functional fine-mapping revealed two independent GWAS regions harboring autoimmune disease risk SNPs with significant effects on microRNA expression. These relate to SNPs associated with Crohn’s disease (CD; rs102275) and rheumatoid arthritis (RA; rs968567), which affect the expression of miR-1908-5p (prs102275=1.44e-20, prs968567=2.54e-14). In addition, an independent CD risk SNP, rs3853824, was found to alter the expression of miR-3614-5p (p=5.70e-7). To support these findings, we demonstrate that GWAS signals for RA and CD were enriched in genes predicted to be targeted by both miRNAs (all with p<0.05).In summary, our study points towards a pathophysiological role of miR-1908-5p and miR- 3614-5p in autoimmunity.

scholarly journals Chemokines

2007 ◽  
Vol 7 ◽  
pp. 224-232 ◽  
Author(s):  
Richard Horuk
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Chemokine Receptors ◽  
Short Review ◽  
Host Defence ◽  
Therapeutic Approaches ◽  
A Site ◽  
Hiv 1

Chemokines are a family of polypeptides that direct the migration of leukocytestoward a site of infection. They play a major role in autoimmune disease and chemokine receptors have recently been found to mediate HIV-1 fusion. In this short review we examine the role of chemokines in host defence and in the pathophysiology of autoimmune diseases. We conclude by discussing various therapeutic approaches that target chemokine receptors and that could be beneficial in disease.

scholarly journals Therapeutic Application of Exosomes in Inflammatory Diseases

2021 ◽  
Vol 22 (3) ◽  
pp. 1144
Author(s):  
Ju Hun Suh ◽  
Hyeon Su Joo ◽  
Eun Be Hong ◽  
Hyeon Ji Lee ◽  
Jung Min Lee
Keyword(s):  
Immune System ◽  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Human Body ◽  
Therapeutic Strategy ◽  
State Of The Art ◽  
Inflammatory Diseases ◽  
Defense System ◽  
Therapeutic Application

Immunomodulation is on the cusp of being an important therapy for treating many diseases, due to the significant role of the immune system in defending the human body. Although the immune system is an essential defense system, overactivity can result in diverse sicknesses such as inflammation and autoimmune disease. Exosomes are emerging as a state-of-the-art therapeutic strategy for treating an overactive immune system. Thus, in this review, we will thoroughly review therapeutic applications of exosomes in various inflammatory and autoimmune diseases. Finally, issues for an outlook to the future of exosomal therapy will be introduced.

TREX1 As a Potential Therapeutic Target for Autoimmune and Inflammatory Diseases

2019 ◽  
Vol 25 (30) ◽  
pp. 3239-3247 ◽  
Author(s):  
Sha-Sha Tao ◽  
Guo-Cui Wu ◽  
Qin Zhang ◽  
Tian-Ping Zhang ◽  
Rui-Xue Leng ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Therapeutic Target ◽  
Mammalian Cells ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Autoimmune Response ◽  
Autoimmune And Inflammatory Diseases ◽  
Functional Mechanisms

Background and Objectives: The 3’ repair exonuclease 1 (TREX1) gene is the major DNA-specific 3’–5 ’exonuclease of mammalian cells which reduces single- and double-stranded DNA (ssDNA and dsDNA) to prevent undue immune activation mediated by the nucleic acid. TREX1 is also a crucial suppressor of selfrecognition that protects the host from inappropriate autoimmune activations. It has been revealed that TREX1 function is necessary to prevent host DNA accumulating after cell death which could actuate an autoimmune response. In the manuscript, we will discuss in detail the latest advancement to study the role of TREX1 in autoimmune disease. Methods: As a pivotal cytoprotective, antioxidant, anti-apoptotic, immunosuppressive, as well as an antiinflammatory molecule, the functional mechanisms of TREX1 were multifactorial. In this review, we will briefly summarize the latest advancement in studying the role of TREX1 in autoimmune disease, and discuss its potential as a therapeutic target for these diseases. Results: Deficiency of TREX1 in human patients and murine models is characterized by systemic inflammation and the disorder of TREX1 functions drives inflammatory responses leading to autoimmune disease. Moreover, much more studies revealed that mutations in TREX1 have been associated with a range of autoimmune disorders. But it is also unclear whether the mutations of TREX1 play a causal role in the disease progression, and whether manipulation of TREX1 has a beneficial effect in the treatment of autoimmune diseases. Conclusion: Integration of functional TREX1 biology into autoimmune diseases may further deepen our understanding of the development and pathogenesis of autoimmune diseases and provide new clues and evidence for the treatment of autoimmune diseases.

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.

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