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Rheumatic Diseases Clinics of North... Nov 1995This article summarizes the most recent findings concerning the clinical relevance of antineutrophil cytoplasmic autoantibody (ANCA) testing for patients with idiopathic... (Review)
Review
This article summarizes the most recent findings concerning the clinical relevance of antineutrophil cytoplasmic autoantibody (ANCA) testing for patients with idiopathic vasculitis and with diseases known to be associated with secondary vasculitis. The clinical value of granular cytoplasmic pattern (c)ANCA (proteinase 3 [PR3]-ANCA) and perinuclear fluorescence pattern (p)ANCA (myeloperoxidase [MPO]-ANCA) testing in Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA), respectively, is now well established; however, the various subspecificities beside myeloperoxidase (MPO), which also include the perinuclear staining pattern, are detectable not only in vasculitis, but equally in a heterogeneous patient population with a spectrum of autoimmune diseases and idiopathic chronic inflammatory diseases of the bowel, liver, and so forth. Future studies must establish the specificity, sensitivity, and role of these pANCA subspecificities usually measured by enzyme-linked immunosorbent assays for distinct disease entities in clinical medicine. In summary, despite the relatively poor understanding of the immunopathogenesis of ANCA-associated disease, cANCA (PR3-ANCA) and pANCA (MPO-ANCA) continue to be important clinical markers of the so-called "ANCA-associated vasculitides" (i.e., WG, MPA, and Churg-Strauss syndrome).
Topics: Antibodies, Antineutrophil Cytoplasmic; Antibody Formation; Autoantibodies; Autoantigens; Autoimmunity; Biomarkers; Fluorescent Antibody Technique, Indirect; Humans; Vasculitis
PubMed: 8592745
DOI: No ID Found -
Expert Review of Proteomics Aug 2009Biomarkers that show high sensitivity and specificity are needed for the early diagnosis and prognosis of cancer. An immune response to cancer is elicited in humans, as... (Review)
Review
Biomarkers that show high sensitivity and specificity are needed for the early diagnosis and prognosis of cancer. An immune response to cancer is elicited in humans, as demonstrated, in part, by the identification of autoantibodies against a number of tumor-associated antigen (TAAs) in sera from patients with different types of cancer. Identification of TAAs and their cognate autoantibodies is a promising strategy for the discovery of relevant biomarkers. During the past few years, three proteomic approaches, including serological identification of antigens by recombinant expression cloning (SEREX), serological proteome analysis (SERPA) and, more recently, protein microarrays, have been the dominant strategies used to identify TAAs and their cognate autoantibodies. In this review, we aim to describe the advantages, drawbacks and recent improvements of these approaches for the study of humoral responses. Finally, we discuss the definition of autoantibody signatures to improve sensitivity for the development of clinically relevant tests.
Topics: Animals; Autoantibodies; Humans; Neoplasms; Proteomics
PubMed: 19681673
DOI: 10.1586/epr.09.56 -
Clinical Reviews in Allergy & Immunology Oct 2022Circulating autoantibodies are a key diagnostic tool in autoimmune hepatitis (AIH), being positive in 95% of the cases if tested according to dedicated guidelines issued... (Review)
Review
Circulating autoantibodies are a key diagnostic tool in autoimmune hepatitis (AIH), being positive in 95% of the cases if tested according to dedicated guidelines issued by the International Autoimmune Hepatitis Group. They also allow the distinction between type 1 AIH, characterized by positive anti-nuclear and/or anti-smooth muscle antibody, and type 2 AIH, characterized by positive anti-liver kidney microsomal type 1 and/or anti-liver cytosol type 1 antibody. Anti-soluble liver antigen is the only AIH-specific autoantibody, and is found in 20-30% of both type 1 and type 2 AIH. Anti-neutrophil cytoplasmic antibody is frequently positive in type 1 AIH, being associated also with inflammatory bowel disease and with primary/autoimmune sclerosing cholangitis. The reference method for autoantibody testing remains indirect immunofluorescence on triple tissue (rodent liver, kidney and stomach), allowing both the detection of the majority of liver-relevant reactivities, including those autoantibodies whose molecular target antigens are unknown. Of note, the current knowledge of the clinical significance of autoantibodies relies on studies based on this technique. However, immunofluorescence requires trained laboratory personnel, is observer-dependent, and lacks standardization, leading to ongoing attempts at replacing this method with automated assays, the sensitivity, and specificity of which, however, require further studies before they can be used as a reliable alternative to immunofluorescence; currently, they may be used as complementary to immunofluorescence.
Topics: Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Fluorescent Antibody Technique, Indirect; Hepatitis, Autoimmune; Humans; Immunologic Tests
PubMed: 34491531
DOI: 10.1007/s12016-021-08888-9 -
Frontiers in Immunology 2019
Topics: Animals; Autoantibodies; Humans
PubMed: 31001243
DOI: 10.3389/fimmu.2019.00484 -
Advances in Experimental Medicine and... 2012Antibody networks have been studied in the past based on the connectivity between idiotypes and anti-idiotypes-antibodies that bind one another. Here we call attention... (Review)
Review
Antibody networks have been studied in the past based on the connectivity between idiotypes and anti-idiotypes-antibodies that bind one another. Here we call attention to a different network of antibodies, antibodies connected by their reactivities to sets of antigens-the antigen-reactivity network. The recent development of antigen microarray chip technology for detecting global patterns of antibody reactivities makes it possible to study the immune system quantitatively using network analysis tools. Here, we review the analyses of IgM and IgG autoantibody reactivities of sera of mothers and their offspring (umbilical cords) to 300 defined self-antigens; the autoantibody reactivities present in cord blood represent the natural autoimmune repertories with which healthy humans begin life and the mothers' reactivities reflect the development of the repertoires in healthy young adults. Comparing the cord and maternal reactivities using several analytic tools led to the following conclusions: (1) The IgG repertoires showed a high correlation between each mother and her newborn; the IgM repertoires of all the cords were very similar and each cord differed from its mother's IgM repertoire. Thus, different humans are born with very similar IgM autoantibodies produced in utero and with unique IgG autoantibodies found in their individual mothers. (2) Autoantibody repertoires appear to be structured into sets of reactivities that are organized into cliques-reactivities to particular antigens are correlated. (3) Autoantibody repertoires are organized as networks of reactivities in which certain key antigen reactivities dominate the network-the dominant antigen reactivities manifest a "causal" relationship to sets of other correlated reactivities. Thus, repertoires of autoantibodies in healthy subjects, the immunological homunculus, are structured in hierarchies of antigen reactivities.
Topics: Adult; Antibody Specificity; Autoantibodies; Autoantigens; Fetal Blood; Gene Expression; Gene Expression Profiling; Genetic Variation; Humans; Immunoglobulin G; Immunoglobulin M; Infant, Newborn; Protein Array Analysis; Protein Interaction Mapping
PubMed: 22903676
DOI: 10.1007/978-1-4614-3461-0_15 -
Methods in Molecular Biology (Clifton,... 2009The advent of the serological identification of antigens by procedures such as cDNA cloning and recombinant protein expression has allowed the direct molecular... (Review)
Review
The advent of the serological identification of antigens by procedures such as cDNA cloning and recombinant protein expression has allowed the direct molecular definition of immunogenic proteins. The phage-display technology provides several advantages over conventional immunoscreening procedures based on plasmid or lambda-phage cDNA libraries. So far, attempts to display open reading frames, such as those encoded by cDNA fragments, on filamentous phages have not been very successful. We managed to develop a strategy based on "folding reporters" which allows filtering out open reading frames from DNA and displaying them on filamentous phages in such a way that they are amenable to subsequent selection or screening. Once the cDNA library of interest is created, phage-display technology is used for selection of novel putative antigens; these are then validated by printing isolated protein on microarray and screening with patients' sera.
Topics: Autoantibodies; Gene Library; High-Throughput Screening Assays; Humans; Models, Biological; Open Reading Frames; Peptide Library; Protein Array Analysis; Recombinant Proteins
PubMed: 19649606
DOI: 10.1007/978-1-60327-394-7_20 -
Biomedicine & Pharmacotherapy =... 1989Recent advances in the understanding of the ontogeny of the normal B cell response and of the molecular mechanisms that are used to generate a diverse B cell repertoire... (Review)
Review
Recent advances in the understanding of the ontogeny of the normal B cell response and of the molecular mechanisms that are used to generate a diverse B cell repertoire have resulted in new approaches to the study of autoimmune diseases. B cell lines with autoantibody specificity can easily be generated from normal individuals. These low affinity and generally polyspecific "natural autoantibodies" have features of a B cell response prior to antigenic stimulation and are encoded by germline or relatively unmutated genes. Pathogenic autoantibodies from autoimmune individuals on the other hand, appear to be higher affinity antibodies that have features of an antigen selected response. The relationship between these two different classes of autoantibodies remains to be determined. Our studies of anti-DNA antibodies in human SLE have revealed that anti-DNA antibodies from unrelated patients share dominant cross-reactive idiotypes. Analysis of monoclonal anti-DNA antibodies bearing two SLE related idiotypes, 3I and F4, have indicated to us that DNA binding activity is acquired by somatic mutation, suggesting that these autoantibodies are not germline encoded but require antigenic stimulation and T cell help. Molecular analysis of genes encoding 3I reactive light chains from a panel of EBV transformed B cell lines have revealed that 3I reactive light chains are nearly all encoded by a member of the VK 1 gene family. Thus for this idiotypic system, there is restricted gene usage to encode anti-DNA antibodies. Further molecular analysis may reveal the structural features that determine idiotype reactivity and autoreactivity and may help determine what features of these genes could account for their preferential expression in SLE patients and their family members.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Antibodies, Antinuclear; Antibody Formation; Autoantibodies; Autoimmune Diseases; Genes, MHC Class II; Humans
PubMed: 2517224
DOI: 10.1016/0753-3322(89)90033-4 -
Clinical Reviews in Allergy & Immunology Oct 2022Autoantibodies represent a hallmark of rheumatoid arthritis (RA), with the rheumatoid factor (RF) and antibodies against citrullinated proteins (ACPA) being the most... (Review)
Review
Autoantibodies represent a hallmark of rheumatoid arthritis (RA), with the rheumatoid factor (RF) and antibodies against citrullinated proteins (ACPA) being the most acknowledged ones. RA patients who are positive for RF and/or ACPA ("seropositive") in general display a different etiology and disease course compared to so-called "seronegative" patients. Still, the seronegative patient population is very heterogeneous and not well characterized. Due to the identification of new autoantibodies and advancements in the diagnosis of rheumatic diseases in the last years, the group of seronegative patients is constantly shrinking. Aside from antibodies towards various post-translational modifications, recent studies describe autoantibodies targeting some native proteins, further broadening the spectrum of recognized antigens. Next to the detection of new autoantibody groups, much research has been done to answer the question if and how autoantibodies contribute to the pathogenesis of RA. Since autoantibodies can be detected years prior to RA onset, it is a matter of debate whether their presence alone is sufficient to trigger the disease. Nevertheless, there is gathering evidence of direct autoantibody effector functions, such as stimulation of osteoclastogenesis and synovial fibroblast migration in in vitro experiments. In addition, autoantibody positive patients display a worse clinical course and stronger radiographic progression. In this review, we discuss current findings regarding different autoantibody types, the underlying disease-driving mechanisms, the role of Fab and Fc glycosylation and clinical implications.
Topics: Arthritis, Rheumatoid; Autoantibodies; Humans; Rheumatoid Factor
PubMed: 34495490
DOI: 10.1007/s12016-021-08890-1 -
Lupus Jul 2016Testing for autoantibodies (AABs) is becoming more and more relevant, not only for diagnosing autoimmune diseases (AIDs) but also for the differentiation of defined AID... (Review)
Review
Testing for autoantibodies (AABs) is becoming more and more relevant, not only for diagnosing autoimmune diseases (AIDs) but also for the differentiation of defined AID subtypes with different clinical manifestations, course and prognosis as well as the very early diagnosis for adequate management in the context of personalized medicine. A major challenge to improve diagnostic accuracy is to harmonize or even standardize AAB analyses. This review presents the results of the 12th Dresden Symposium on Autoantibodies that focused on several aspects of improving autoimmune diagnostics. Topics that are addressed include the International Consensus on ANA Patterns (ICAP) and the International Autoantibody Standardization (IAS) initiatives, the optimization of diagnostic algorithms, the description and evaluation of novel disease-specific AABs as well as the development and introduction of novel assays into routine diagnostics. This review also highlights important developments of recent years, most notably the improvement in diagnosing and predicting the course of rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, and of autoimmune neurological, gastrointestinal and liver diseases; the potential diagnostic role of anti-DFS70 antibodies and tumor-associated AABs. Furthermore, some hot topics in autoimmunity regarding disease pathogenesis and management are described.
Topics: Autoantibodies; Autoimmune Diseases; Autoimmunity; Congresses as Topic; Early Diagnosis; Germany; Humans
PubMed: 27252254
DOI: 10.1177/0961203316644337 -
Autoimmunity Reviews Jul 2006Many autoimmune diseases are characterized by autoantibody subsets that are associated with specific clinical manifestations. The primary genetic associations of these... (Review)
Review
Many autoimmune diseases are characterized by autoantibody subsets that are associated with specific clinical manifestations. The primary genetic associations of these autoantibodies are with MHC genes, most specifically HLA class II, which in many instances better explain the HLA association of the disease per se. It is noteworthy that certain genes and haplotypes, notably HLA-DRB1*0301, DQA1*0501, DQB1*0201 in Caucasians and DRB1*0405, DQA1*03, DQB1*0401 in Asians, as well as PTPN22, seem to be associated with a variety of autoimmune diseases. On the other hand, others are more disease specific (HLA-DRB1*11 for systemic sclerosis and HLA-DRB1 alleles encoding the "shared epitope" in RA) as well as non MHC genes, such as FcyRIIa and IIIa in SLE, the beta2 glycoprotein I gene in the aPL syndrome, and the TSHR gene in Graves' disease). Autoantibody responses also are influenced by the presence of specific MHC and non-MHC genes which may not be associated with the disease per se. These novel associations offer new clues not only to pathogenesis but also to potential therapeutic targets.
Topics: Animals; Autoantibodies; Autoimmune Diseases; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Humans; Major Histocompatibility Complex; Mice
PubMed: 16890892
DOI: 10.1016/j.autrev.2005.10.012