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The Journal of Dermatology Jul 2024Idiopathic inflammatory myopathies (IIMs) are divided into polymyositis and dermatomyositis (DM) with specific cutaneous manifestation. Several myositis-specific... (Review)
Review
Idiopathic inflammatory myopathies (IIMs) are divided into polymyositis and dermatomyositis (DM) with specific cutaneous manifestation. Several myositis-specific autoantibodies (MSAs) have been identified in IIMs and were found to be associated with distinct clinical features, including anti-synthetase syndrome (ASyS) and immune-mediated necrotizing myopathy (IMNM). Moreover, MSA-related clinical features have been identified even within DM. Although MSAs are valuable for the diagnosis of IIMs, the pathogenic roles of these antibodies remain unknown. To investigate the pathogenesis of IIMs, classical murine models of autoimmune myositis, experimental autoimmune myositis, and C protein-induced myositis have been established by immunization with muscle-specific antigens, myosin, and myosin-binding skeletal C protein, respectively. To according to MSA-related autoimmunity, a murine model of ASyS was generated by immunization with a murine recombinant histidyl-transfer RNA (tRNA) synthetase, Jo-1, in which muscle and lung inflammation are induced depending on acquired immunity. Furthermore, it was found that the transfer of human Immunoglobulin G (IgGs) from patients with IMNM, comprising anti-signal recognition particles and anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibodies, induced complement-mediated myositis in recipient mice. We found that CD8 T cell-mediated myositis can be established depending on autoimmunity against transcriptional intermediary factor 1γ (TIF1γ), an autoantigen for MSAs induced by recombinant human TIF1γ immunization. These new murine models reflecting MSA-associated IIMs will reveal the immunological mechanisms underlying IIMs.
Topics: Animals; Disease Models, Animal; Mice; Myositis; Humans; Autoantibodies; Autoantigens
PubMed: 38321631
DOI: 10.1111/1346-8138.17142 -
Nature Reviews. Rheumatology Oct 2016
Topics: Arthritis, Rheumatoid; Autoantibodies; Humans; Peptides, Cyclic; Rheumatoid Factor
PubMed: 27627867
DOI: 10.1038/nrrheum.2016.151 -
Rheumatology International 1992
Review
Autoantibodies against small cytoplasmic ribonucleoproteins: the anti-Ro/SS-A and anti-La/SS-B autoimmune response. A review of autoantibody detection, autoantigen composition, autoantibody-disease associations and possible etiologic mechanisms.
Topics: Animals; Antibodies, Antinuclear; Antibody Formation; Autoantibodies; Autoimmunity; Cytoplasm; Humans; Ribonucleoproteins
PubMed: 1439479
DOI: 10.1007/BF00274932 -
Clinica Chimica Acta; International... Aug 2016Significant progress has been made in understanding the role and diversity of autoantibodies in the pathogenesis, diagnosis and management of paraneoplastic syndrome...
BACKGROUND
Significant progress has been made in understanding the role and diversity of autoantibodies in the pathogenesis, diagnosis and management of paraneoplastic syndrome (PNS) and related autoimmune neurologic diseases. We evaluated the positivity rates for diverse autoantibody panels to rationalize testing strategies and utilization.
METHODS
The result patterns for different autoantibody panels for PNS offered at 2 reference laboratories in the U.S. were retrospectively reviewed for the same period. The positivity rates were evaluated and compared for specific autoantibodies within panels offered at both laboratories.
RESULTS
For the Hu, Ri, Yo, and amphiphysin antibodies offered by both laboratories, no significant difference in positivity rates was observed. The positivity rates for non-classic PNS markers were 0% [AGNA and PCCA-Tr], and 0.06% [ANNA-3 and PCAC-2] while the prevalence of antibodies associated with neuromuscular autoimmunity varied from 1.40% to 4.44% [Striated muscle, AChR binding, ganglionic AChR, VGCC, P/Q- and N-type VGCC].
CONCLUSIONS
The data suggest that test utilization could be substantially improved based on ordering practice geared towards clinical manifestations and prevalence of autoantibodies. Concerted efforts towards streamlining diagnostic algorithms based on risk, clinical manifestations, characterization of autoantibodies and their associations as well as therapeutic strategies are needed.
Topics: Adolescent; Adult; Aged; Algorithms; Autoantibodies; Biomarkers; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Paraneoplastic Syndromes; Young Adult
PubMed: 27287529
DOI: 10.1016/j.cca.2016.06.006 -
Journal of Autoimmunity Sep 2023ObjectiveMultiple spliceosome components are known autoantigens in systemic sclerosis (SSc). Here we aim to identify new and characterize rare anti-spliceosomal...
ObjectiveMultiple spliceosome components are known autoantigens in systemic sclerosis (SSc). Here we aim to identify new and characterize rare anti-spliceosomal autoantibodies in patients with SSc without known autoantibody specificity. MethodsSera that precipitated spliceosome subcomplexes, as detected by immunoprecipitation-mass spectrometry (IP-MS), were identified from a database of 106 patients with SSc without known autoantibody specificity. New autoantibody specificities were confirmed with immunoprecipitation-western blot. The IP-MS pattern of new anti-spliceosomal autoantibodies was compared with anti-U1 RNP-positive sera of patients with different systemic autoimmune rheumatic diseases and anti-SmD-positive sera of patients with systemic lupus erythematosus (n = 24). ResultsThe NineTeen Complex (NTC) was identified and confirmed as new spliceosomal autoantigen in one patient with SSc. U5 RNP, as well as additional splicing factors, were precipitated by the serum of another patient with SSc. The IP-MS patterns of anti-NTC and anti-U5 RNP autoantibodies were distinct from those of anti-U1 RNP- and anti-SmD-positive sera. Furthermore, there was no difference in IP-MS patterns between a limited number of anti-U1 RNP-positive sera of patients with different systemic autoimmune rheumatic diseases. ConclusionAnti-NTC autoantibodies are a new anti-spliceosomal autoantibody specificity, here first identified in a patient with SSc. Anti-U5 RNP autoantibodies are a distinct but rare anti-spliceosomal autoantibody specificity. All major spliceosomal subcomplexes have now been described as target of autoantibodies in systemic autoimmune diseases.
Topics: Humans; Autoantibodies; Spliceosomes; Scleroderma, Systemic; Lupus Erythematosus, Systemic; Antibodies, Antinuclear; Autoantigens; Rheumatic Diseases
PubMed: 37302272
DOI: 10.1016/j.jaut.2023.103056 -
Presse Medicale (Paris, France : 1983) Jan 2014Activation and differentiation of autoreactive B-lymphocytes lead to the production of autoantibodies, which are thus the direct consequence of the autoimmune process.... (Review)
Review
Activation and differentiation of autoreactive B-lymphocytes lead to the production of autoantibodies, which are thus the direct consequence of the autoimmune process. They often constitute biomarkers of autoimmune diseases and are measured by tests displaying various diagnosis sensitivity and specificity. Autoantibody titers can be correlated to the disease activity and certain autoantibody populations associated with particular clinical manifestations or tissue lesions. The demonstration that autoantibodies appear years before the onset of autoimmune diseases indicates that their presence in healthy individuals may be a predictive marker of the occurrence of disease. Certain autoantibodies could also be predictive markers of a therapeutic response to biologics and of the occurrence of side effects as well. Thus, autoantibodies are useful tools in the diagnosis and the management of patients with organ specific or non-organ specific autoimmune diseases at different steps of the autoimmune process.
Topics: Autoantibodies; Autoimmune Diseases; Biomarkers; Humans; Sensitivity and Specificity
PubMed: 24387998
DOI: 10.1016/j.lpm.2012.11.025 -
Pediatric Diabetes Dec 2022Increased level of glycated hemoglobin (HbA1c) is associated with type 1 diabetes onset that in turn is preceded by one to several autoantibodies against the pancreatic...
OBJECTIVE
Increased level of glycated hemoglobin (HbA1c) is associated with type 1 diabetes onset that in turn is preceded by one to several autoantibodies against the pancreatic islet beta cell autoantigens; insulin (IA), glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8). The risk for type 1 diabetes diagnosis increases by autoantibody number. Biomarkers predicting the development of a second or a subsequent autoantibody and type 1 diabetes are needed to predict disease stages and improve secondary prevention trials. This study aimed to investigate whether HbA1c possibly predicts the progression from first to a subsequent autoantibody or type 1 diabetes in healthy children participating in the Environmental Determinants of Diabetes in the Young (TEDDY) study.
RESEARCH DESIGN AND METHODS
A joint model was designed to assess the association of longitudinal HbA1c levels with the development of first (insulin or GAD autoantibodies) to a second, second to third, third to fourth autoantibody or type 1 diabetes in healthy children prospectively followed from birth until 15 years of age.
RESULTS
It was found that increased levels of HbA1c were associated with a higher risk of type 1 diabetes (HR 1.82, 95% CI [1.57-2.10], p < 0.001) regardless of first appearing autoantibody, autoantibody number or type. A decrease in HbA1c levels was associated with the development of IA-2A as a second autoantibody following GADA (HR 0.85, 95% CI [0.75, 0.97], p = 0.017) and a fourth autoantibody following GADA, IAA and ZnT8A (HR 0.90, 95% CI [0.82, 0.99], p = 0.036). HbA1c trajectory analyses showed a significant increase of HbA1c over time (p < 0.001) and that the increase is more rapid as the number of autoantibodies increased from one to three (p < 0.001).
CONCLUSION
In conclusion, increased HbA1c is a reliable time predictive marker for type 1 diabetes onset. The increased rate of increase of HbA1c from first to third autoantibody and the decrease in HbA1c predicting the development of IA-2A are novel findings proving the link between HbA1c and the appearance of autoantibodies.
Topics: Child; Humans; Autoantibodies; Biomarkers; Diabetes Mellitus, Type 1; Glutamate Decarboxylase; Glycated Hemoglobin; Insulin
PubMed: 36082496
DOI: 10.1111/pedi.13413 -
Scandinavian Journal of Rheumatology 1997Autoantibody determinations are frequently used by rheumatologists to establish the diagnosis or assess follow up clinical status in patients with connective tissue... (Review)
Review
Autoantibody determinations are frequently used by rheumatologists to establish the diagnosis or assess follow up clinical status in patients with connective tissue diseases. Such autoantibodies are often presumed to have harmful effects, particularly since some such as anti-native DNA or anti-Ro have frequently been related to tissue damage or to functional impairments. However, there are many other autoantibodies which react with antigenic components of normal autologous tissues which have not been demonstrated to have self-damaging or harmful effects. Some of these autoantibodies may actually represent natural built-in mechanisms of feed-back inhibition, serving to modulate normal physiologic function. Autoantibodies may be compared to chameleons since their function or quality is often judged by the company they keep or by their anatomical localization. Since many autoantibodies to intra-cellular products seem to react with active sites of important biologic molecules, they may provide us with a much sharper image of a number of natural cellular functions.
Topics: Autoantibodies; Autoimmune Diseases; Humans
PubMed: 9137319
DOI: 10.3109/03009749709115822 -
Critical Reviews in Immunology 1986The manuscript will deal with various aspects of the origin of autoantibody formation in relationship with idiotypy. The proposed analysis will cover three major... (Review)
Review
The manuscript will deal with various aspects of the origin of autoantibody formation in relationship with idiotypy. The proposed analysis will cover three major aspects: (1) overview of the published data on idiotypic characterization of autoantibodies in various systems by conventional serologic investigation; (2) presentation of the structural and genetic data available for autoantibodies; and (3) description of the most significant experiment of in vivo manipulation of autoantibody production using idiotypy as the central element for immune regulation. The manuscript will also discuss some theoretical aspects of regulation by idiotype and its possible relevance to improve our understanding of autoreactivity as well as the pathogenesis of certain autoimmune diseases.
Topics: Animals; Autoantibodies; Cross Reactions; DNA; Genes; Genes, MHC Class II; Humans; Immune Tolerance; Immunoglobulin Idiotypes; Models, Biological; Thyroglobulin
PubMed: 3089685
DOI: No ID Found -
Methods in Molecular Biology (Clifton,... 2016The use of peptide microarrays for epitope mapping of autoantibodies greatly facilitates the early diagnosis of allergic, cytotoxin-associated diseases and especially...
The use of peptide microarrays for epitope mapping of autoantibodies greatly facilitates the early diagnosis of allergic, cytotoxin-associated diseases and especially inflammatory diseases. A common approach to create the microarrays utilizes nitrocellulose-coated glass slides for peptide probe binding, which is based on surface adsorption. Advantages of this method include excellent peptide binding capacity and long-term stability. To ensure equal accessibility to all antibodies on the peptide microarray during epitope mapping, all probes are immobilized in a random manner, thus avoiding concentration-dependent effects on signal intensity.In this chapter, we provide a step-by-step protocol on how to construct the peptide microarrays and perform epitope mapping of autoantibodies using them. Finally we present a comparative approach for the evaluation of the data.
Topics: Autoantibodies; Blood Specimen Collection; Epitope Mapping; Humans; Peptides; Protein Array Analysis
PubMed: 26614078
DOI: 10.1007/978-1-4939-3136-1_15