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Arthritis Research & Therapy Jul 2017Testing for the presence of antinuclear antibodies (ANAs) is a key step in the diagnosis of systemic lupus erythematosus (SLE) and other systemic autoimmune rheumatic... (Review)
Review
Testing for the presence of antinuclear antibodies (ANAs) is a key step in the diagnosis of systemic lupus erythematosus (SLE) and other systemic autoimmune rheumatic diseases (SARD). The standard slide-based indirect immunofluorescence (IIF) test is widely used, but is limited by a relative lack of specificity for SLE and not all SARD-ANAs are detected. Alternative immunoassays that might offer enhanced diagnostic and prognostic information have evolved, and some of these have entered clinical practice. This review summarizes the current state of ANA testing and multiplex techniques for detecting other autoantibodies, the possibility of point-of-care testing, and approaches for applications in early disease stages.
Topics: Antibodies, Antinuclear; Autoantibodies; Humans; Immunoassay; Rheumatic Diseases
PubMed: 28738887
DOI: 10.1186/s13075-017-1380-3 -
Journal of Translational Medicine Nov 2017Evidence supports the existence of different subphenotypes in systemic lupus erythematosus (SLE) and the pivotal role of cytokines and autoantibodies, which interact in...
BACKGROUND
Evidence supports the existence of different subphenotypes in systemic lupus erythematosus (SLE) and the pivotal role of cytokines and autoantibodies, which interact in a highly complex network. Thus, understanding how these complex nonlinear processes are connected and observed in real-life settings is a major challenge. Cluster approaches may assist in the identification of these subphenotypes, which represent such a phenomenon, and may contribute to the development of personalized medicine. Therefore, the relationship between autoantibody and cytokine clusters in SLE was analyzed.
METHODS
This was an exploratory study in which 67 consecutive women with established SLE were assessed. Clinical characteristics including disease activity, a 14-autoantibody profile, and a panel of 15 serum cytokines were measured simultaneously. Mixed-cluster methodology and bivariate analyses were used to define autoantibody and cytokine clusters and to identify associations between them and related variables.
RESULTS
First, three clusters of autoantibodies were defined: (1) neutral, (2) antiphospholipid antibodies (APLA)-dominant, and (3) anti-dsDNA/ENA-dominant. Second, eight cytokines showed levels above the threshold thus making possible to find 4 clusters: (1) neutral, (2) chemotactic, (3) G-CSF dominant, and (4) IFNα/Pro-inflammatory. Furthermore, the disease activity was associated with cytokine clusters, which, in turn, were associated with autoantibody clusters. Finally, when all biomarkers were included, three clusters were found: (1) neutral, (2) chemotactic/APLA, and (3) IFN/dsDNA, which were also associated with disease activity.
CONCLUSION
These results support the existence of three SLE cytokine-autoantibody driven subphenotypes. They encourage the practice of personalized medicine, and support proof-of-concept studies.
Topics: Adult; Antibodies, Antinuclear; Autoantibodies; Cluster Analysis; Cross-Sectional Studies; Cytokines; Female; Humans; Lupus Erythematosus, Systemic; Middle Aged; Young Adult
PubMed: 29178890
DOI: 10.1186/s12967-017-1345-y -
BMB Reports Dec 2012In the process of tumorigenesis, normal cells are remodeled to cancer cells and protein expression patterns are changed to those of tumor cells. A newly formed tumor... (Review)
Review
In the process of tumorigenesis, normal cells are remodeled to cancer cells and protein expression patterns are changed to those of tumor cells. A newly formed tumor microenvironment elicits the immune system and, as a result, a humoral immune response takes place. Although the tumor antigens are undetectable in sera at the early stage of tumorigenesis, the nature of an antibody amplification response to antigens makes tumor-associated autoantibodies as promising early biomarkers in cancer diagnosis. Moreover, the recent development of proteomic techniques that make neo-epitopes of tumor-associated autoantigens discovered concomitantly has opened a new area of 'immuno-proteomics', which presents tumor-associated autoantibody signatures and confers information to redefine the process of tumorigenesis. In this article, the strategies recently used to identify and validate serum autoantibodies are outlined and tumor-associated antigens suggested until now as diagnostic/prognostic biomarkers in various tumor types are reviewed. Also, the meaning of autoantibody signatures and their clinical utility in personalized medicine are discussed.
Topics: Autoantibodies; Autoantigens; Biomarkers, Tumor; Humans; Neoplasms; Prognosis; Protein Array Analysis; Proteomics
PubMed: 23261052
DOI: 10.5483/bmbrep.2012.45.12.236 -
Frontiers in Immunology 2022Anti-neural autoantibody-associated psychiatric disease is a novel field in immunopsychiatry that has been attracting attention thanks to its potentially positive... (Review)
Review
BACKGROUND
Anti-neural autoantibody-associated psychiatric disease is a novel field in immunopsychiatry that has been attracting attention thanks to its potentially positive therapeutic outcome and distinct prognosis compared with non-organic psychiatric disease. This review aims to describe recent novel technological developments for improving diagnostics in the field of autoantibody-related psychiatric disease.
METHODS
We screened for relevant articles in PubMed for this narrative article. We focused on research methods such as neuroimaging, immune cells and inflammation markers, and molecular biomarkers in human biofluids like serum and cerebrospinal fluid and plasma proteomics.
RESULTS
We introduce several novel methods for investigating autoinflammation with the aim of optimizing therapies for autoantibody-associated psychiatric disease. We describe measuring the translocator protein 18kDa in activated microglia via positron emission tomography imaging, brain volumetric assessment, flow cell cytometry of cerebrospinal fluid and blood, and blood biological probes as well as psychopathological cues to help us gain insights into diagnosing inflammation and brain damage better in psychiatric patients presenting a suspected autoimmune etiology.
CONCLUSION
Our short methodological review provides an overview of recent developments in the field of autoantibody-related immunopsychiatry. More research is needed to prove their usefulness in diagnosing and treating autoantibody-associated psychiatric disease and its subtypes.
Topics: Autoantibodies; Biomarkers; Humans; Inflammation; Mental Disorders; Technology
PubMed: 35711412
DOI: 10.3389/fimmu.2022.867229 -
Seminars in Immunology Apr 2012Lung transplantation is considered a definitive treatment for many lung diseases. However, rejection and other pathologic entities are major causes of morbidity and... (Review)
Review
Lung transplantation is considered a definitive treatment for many lung diseases. However, rejection and other pathologic entities are major causes of morbidity and mortality for lung transplant recipients. Primary graft dysfunction (PGD) and obliterative bronchiolitis (OB) are the leading causes of early and late mortality, respectively. While the immune basis of PGD has not been clearly defined, evidence is emerging about roles for autoantibodies in this process. Similarly, the pathogenesis of OB has been linked recently to autoimmunity. This review will highlight the current understanding of autoantibodies in PGD and OB post lung transplantation.
Topics: Animals; Autoantibodies; Bronchiolitis Obliterans; Chronic Disease; Disease Models, Animal; Graft Rejection; Humans; Lung Transplantation; Mice; Primary Graft Dysfunction; Rats
PubMed: 21925897
DOI: 10.1016/j.smim.2011.08.020 -
Blood Reviews Sep 2022Immunodeficiency syndromes represent a diverse group of inherited and acquired disorders, characterized by a spectrum of clinical manifestations, including recurrent... (Review)
Review
Immunodeficiency syndromes represent a diverse group of inherited and acquired disorders, characterized by a spectrum of clinical manifestations, including recurrent infections, autoimmunity, lymphoproliferation and malignancy. Autoantibodies against various self-antigens reflect the immune dysregulation underlying these disorders, and could contribute to certain clinical findings, such as susceptibility to opportunistic infections, cytopenia of different hematopoietic lineages, and organ-specific autoimmune diseases. The mechanism of autoantibody production in the context of immunodeficiency remains largely unknown but is likely shaped by both intrinsic genetic aberrations and extrinsic exposures to possible infectious agents. These autoantibodies if harbor neutralizing activities and reach certain levels in the circulation, could disrupt the biological functions of their targets, resulting in specific clinical manifestations. Herein, we reviewed the prevalence of autoantibodies against cytokines, hematopoietic cells and organ-specific antigens in immunodeficiency syndromes and examined their associations with certain clinical findings. Moreover, the potential mechanism of autoantibody production was also discussed. These may shed light on the development of mechanism-based therapies to reset the dysregulated immune system in immunodeficient patients.
Topics: Autoantibodies; Autoimmune Diseases; Autoimmunity; Cytokines; Humans; Syndrome
PubMed: 35428517
DOI: 10.1016/j.blre.2022.100948 -
Cellular & Molecular Immunology Feb 2021Autoimmune neurological disorders, including neuromyelitis optica spectrum disorder, anti-N-methyl-D-aspartate receptor encephalitis, anti-MOG antibody-associated... (Review)
Review
Autoimmune neurological disorders, including neuromyelitis optica spectrum disorder, anti-N-methyl-D-aspartate receptor encephalitis, anti-MOG antibody-associated disorders, and myasthenia gravis, are clearly defined by the presence of autoantibodies against neurological antigens. Although these autoantibodies have been heavily studied for their biological activities, given the heterogeneity of polyclonal patient samples, the characteristics of a single antibody cannot be definitively assigned. This review details the findings of polyclonal serum and CSF studies and then explores the advances made by single-cell technologies to the field of antibody-mediated neurological disorders. High-resolution single-cell methods have revealed abnormalities in the tolerance mechanisms of several disorders and provided further insight into the B cells responsible for autoantibody production. Ultimately, several factors, including epitope specificity and binding affinity, finely regulate the pathogenic potential of an autoantibody, and a deeper appreciation of these factors may progress the development of targeted immunotherapies for patients.
Topics: Animals; Autoantibodies; Autoimmune Diseases of the Nervous System; B-Lymphocytes; Humans; Single-Cell Analysis
PubMed: 32728203
DOI: 10.1038/s41423-020-0510-z -
Journal of Neuroinflammation Aug 2016Our knowledge of autoantibody-associated diseases of the central (CNS) and peripheral (PNS) nervous systems has expanded greatly over the recent years. A number of... (Review)
Review
BACKGROUND
Our knowledge of autoantibody-associated diseases of the central (CNS) and peripheral (PNS) nervous systems has expanded greatly over the recent years. A number of extracellular and intracellular autoantigens have been identified, and there is no doubt that this field will continue to expand as more autoantigens are discovered as a result of improved clinical awareness and methodological practice. In recent years, interest has shifted to uncover the target epitopes of these autoantibodies.
MAIN BODY
The purpose of this review is to discuss the mapping of the epitope targets of autoantibodies in CNS and PNS antibody-mediated disorders, such as N-methyl-D-aspartate receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), leucine-rich glioma-inactivated protein 1 (Lgi1), contactin-associated protein-like 2 (Caspr2), myelin oligodendrocyte glycoprotein (MOG), aquaporin-4 (AQP4), 65 kDa glutamic acid decarboxylase (GAD65), acetylcholine receptor (AChR), muscle-specific kinase (MuSK), voltage-gated calcium channel (VGCC), neurofascin (NF), and contactin. We also address the methods used to analyze these epitopes, the relevance of their determination, and how this knowledge can inform studies on autoantibody pathogenicity. Furthermore, we discuss triggers of autoimmunity, such as molecular mimicry, ectopic antigen expression, epitope spreading, and potential mechanisms for the rising number of double autoantibody-positive patients.
CONCLUSIONS
Molecular insights into specificity and role of autoantibodies will likely improve diagnosis and treatment of CNS and PNS neuroimmune diseases.
Topics: Animals; Autoantibodies; Autoantigens; Autoimmune Diseases of the Nervous System; Epitope Mapping; Epitopes; Humans; Nervous System Autoimmune Disease, Experimental
PubMed: 27577085
DOI: 10.1186/s12974-016-0678-4 -
Neurobiology of Disease Jan 2021Over the past decades, the identification of autoimmune encephalitis in which patients express autoantibodies directed against neurotransmitter receptors has generated... (Review)
Review
Over the past decades, the identification of autoimmune encephalitis in which patients express autoantibodies directed against neurotransmitter receptors has generated great hope to shed new light on the molecular mechanisms underpinning neurological and psychiatric conditions. Among these autoimmune encephalitides, the discovery of autoantibodies directed against the glutamatergic NMDA receptor (NMDAR-Ab), in the anti-NMDAR encephalitis, has provided some key information on how complex neuropsychiatric symptoms can be caused by a deficit in NMDAR signalling. Yet, NMDAR-Abs have also been detected in several neurological and psychiatric conditions, as well as in healthy individuals. In addition, these various NMDAR-Abs appear to have different molecular properties and pathogenicities onto receptors and synaptic functions. Here, we discuss the current view on the variety of NMDAR-Abs and, in particular, how these autoantibodies can lead to receptor dysfunction in neuronal networks. Since our mechanistic understanding on patients' NMDAR-Abs is still in its infancy, several complementary processes can be proposed and further in-depth molecular and cellular investigations will surely reveal key insights. Autoantibodies represent a great opportunity to gain knowledge on the etiology of neuropsychiatric disorders and pave the way for innovative therapeutic strategies. ONE SENTENCE SUMMARY: Current view on patients' autoantibody against NMDAR.
Topics: Animals; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Autoantibodies; Autoantigens; Autoimmunity; Humans
PubMed: 33166697
DOI: 10.1016/j.nbd.2020.105161 -
Clinical Reviews in Allergy & Immunology Oct 2022Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by diverse serological autoantibodies. Anti-dsDNA antibodies are involved in multiple... (Review)
Review
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by diverse serological autoantibodies. Anti-dsDNA antibodies are involved in multiple organ damage, especially the kidney, skin, and central nervous system. Anti-dsDNA antibodies play a pivotal role in SLE, and researchers have developed therapeutic strategies targeting these antibodies. Approaches to reduce anti-dsDNA antibodies via B cell targeted biologics against B cell surface antigens, B cell survival factors, or Bruton's tyrosine kinase have effectively eliminated B cells. However, their non-specific depletion hampers normal immune system functioning and limits the therapeutic benefits. Thus, scientists have attempted anti-dsDNA antibodies or lupus-specific strategies, such as the immature dendritic cell vaccine and immunoadsorption. Recently, synthetic mimic peptides (hCDR1, pCONs, DWEYS, FISLE-412, and ALW) that directly block anti-dsDNA autoantibodies have attracted attention, which could ameliorate lupus, decrease the serological autoantibody titer, reduce the deposition of renal autoantibodies, and improve pathological performance. These potent small peptide molecules are well tolerated, non-toxic, and non-immunogenic, which have demonstrated a benign safety profile and are expected to be hopeful candidates for SLE management. In this review, we clarify the role of anti-dsDNA antibodies in SLE, mainly focus on the current strategies targeting anti-dsDNA antibodies, and discuss their potential clinical value.
Topics: Antibodies, Antinuclear; Autoantibodies; B-Lymphocytes; Humans; Lupus Erythematosus, Systemic; Peptides
PubMed: 34542806
DOI: 10.1007/s12016-021-08898-7