The Experts below are selected from a list of 231 Experts worldwide ranked by ideXlab platform
Henry A Homburger - One of the best experts on this subject based on the ideXlab platform.
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clinical features of 39 patients with antibodies to extractable Nuclear Antigens despite negative antiNuclear antibodies evidence for autoimmunity including neurologic and connective tissue diseases
Medicine, 2005Co-Authors: John M Davis, Henry A Homburger, Kevin G Moder, Steven R YtterbergAbstract:Systemic lupus erythematosus (SLE) rarely presents with a negative antiNuclear antibody (ANA). Although antibodies to extractable Nuclear Antigens (ENA) are sometimes ordered despite a negative ANA, it is unclear if this contributes to the diagnosis of SLE or other forms of connective tissue disease (CTD). We reviewed 39 patients with anti-ENA antibodies despite a negative ANA during a 1-year period to determine the presence of SLE or other CTD. Several patients had clinical features suggestive of CTD, including 1 with possible SLE. A number of patients had neurologic disorders, especially peripheral neuropathy. In this study, the finding of anti-ENA despite negative ANA was associated with neurologic disorders and CTD. This may represent test bias or false-positive anti-ENA assays or false-negative ANA assays, or may imply immune-related mechanisms not previously described.
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guidelines for clinical use of the antiNuclear antibody test and tests for specific autoantibodies to Nuclear Antigens
Archives of Pathology & Laboratory Medicine, 2000Co-Authors: A Kavanaugh, Russell H Tomar, John D Reveille, Daniel H Solomon, Henry A HomburgerAbstract:c The following guideline presents a series of recommendations based on published medical literature for use of the antiNuclear antibody (ANA) test and tests for specific autoantibodies to Nuclear Antigens in the diagnostic evaluation, prognostic assessment, and monitoring of patients with systemic rheumatic diseases. The guideline emphasizes the need for clinical evaluation to improve the usefulness of test results in patient management. Consideration is given to appropriate use of the generic ANA test in the initial evaluation of patients with signs and symptoms of a systemic rheumatic disease, the evaluation of patients suspected of having lupus erythematosus, use in clinical situations in which the ANA test is required to establish a disease diagnosis, and identification of clinical situations in which the ANA test has little value. Sections are also devoted to recommendations aimed at improving the analytic methods used to detect and measure ANA and specific autoantibodies to Nuclear Antigens and to the appropriate use of tests for specific autoantibodies in several disease situations that commonly occur in patients with suspected or documented systemic rheumatic diseases. Emphasis is placed on the use of these tests only in situations in which the test results can be expected to provide information necessary for clinical decision making. Those tests of limited medical usefulness and situations in which test results are likely to be misleading are also identified. (Arch Pathol Lab Med. 2000;124:71‐81)
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guidelines for clinical use of the antiNuclear antibody test and tests for specific autoantibodies to Nuclear Antigens american college of pathologists
Archives of Pathology & Laboratory Medicine, 2000Co-Authors: A Kavanaugh, Russell H Tomar, John D Reveille, Daniel H Solomon, Henry A HomburgerAbstract:The following guideline presents a series of recommendations based on published medical literature for use of the antiNuclear antibody (ANA) test and tests for specific autoantibodies to Nuclear Antigens in the diagnostic evaluation, prognostic assessment, and monitoring of patients with systemic rheumatic diseases. The guideline emphasizes the need for clinical evaluation to improve the usefulness of test results in patient management. Consideration is given to appropriate use of the generic ANA test in the initial evaluation of patients with signs and symptoms of a systemic rheumatic disease, the evaluation of patients suspected of having lupus erythematosus, use in clinical situations in which the ANA test is required to establish a disease diagnosis, and identification of clinical situations in which the ANA test has little value. Sections are also devoted to recommendations aimed at improving the analytic methods used to detect and measure ANA and specific autoantibodies to Nuclear Antigens and to the appropriate use of tests for specific autoantibodies in several disease situations that commonly occur in patients with suspected or documented systemic rheumatic diseases. Emphasis is placed on the use of these tests only in situations in which the test results can be expected to provide information necessary for clinical decision making. Those tests of limited medical usefulness and situations in which test results are likely to be misleading are also identified.
W.c. Miller - One of the best experts on this subject based on the ideXlab platform.
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Practical Evaluation of Methods for Detection and Specificity of Autoantibodies to Extractable Nuclear Antigens
Clinical and Vaccine Immunology, 2004Co-Authors: James D Folds, K. Freeman, A. Peace-brewer, J. L. Schmitz, Sarah-michelle Orton, W.c. MillerAbstract:Detection and specificity of autoantibodies against extractable Nuclear Antigens (ENA) play a critical role in the diagnosis and management of autoimmune disease. Historically, the detection of these antibodies has employed double immunodiffusion (DID). Autoantibody specificity was correlated with diagnoses by this technique. Enzyme immunoassays have been developed by multiple manufacturers to detect and identify the specificity ENA autoantibodies. To address the relationship of ENA detection by DID and enzyme immunoassay, the performances of five immunoassays were compared. These included two DID and three enzyme-linked immunoassays (ELISA) (both screening and individual antigen profile kits). The sample set included 83 ENA-positive, antiNuclear-antibody (ANA)-positive specimens, 77 ENA-negative, ANA-positive specimens, and 20 ENA- and ANA-negative specimens. Sensitivity and specificity were calculated by two methods: first, by using the in-house DID result as the reference standard, and second, by using latent class analysis, which evaluates each kit result independently. Overall, the results showed that the ELISA methods were more sensitive for detection of ENA autoantibodies than DID techniques, but presence and/or specific type of ENA autoantibody did not always correlate with the patient's clinical presentation. Regardless of the testing strategy an individual laboratory uses, clear communication with the clinical staff regarding the significance of a positive result is imperative. The laboratory and the clinician must both be aware of the sensitivity and specificity of each testing method in use in the clinical laboratory.
A Kavanaugh - One of the best experts on this subject based on the ideXlab platform.
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guidelines for clinical use of the antiNuclear antibody test and tests for specific autoantibodies to Nuclear Antigens
Archives of Pathology & Laboratory Medicine, 2000Co-Authors: A Kavanaugh, Russell H Tomar, John D Reveille, Daniel H Solomon, Henry A HomburgerAbstract:c The following guideline presents a series of recommendations based on published medical literature for use of the antiNuclear antibody (ANA) test and tests for specific autoantibodies to Nuclear Antigens in the diagnostic evaluation, prognostic assessment, and monitoring of patients with systemic rheumatic diseases. The guideline emphasizes the need for clinical evaluation to improve the usefulness of test results in patient management. Consideration is given to appropriate use of the generic ANA test in the initial evaluation of patients with signs and symptoms of a systemic rheumatic disease, the evaluation of patients suspected of having lupus erythematosus, use in clinical situations in which the ANA test is required to establish a disease diagnosis, and identification of clinical situations in which the ANA test has little value. Sections are also devoted to recommendations aimed at improving the analytic methods used to detect and measure ANA and specific autoantibodies to Nuclear Antigens and to the appropriate use of tests for specific autoantibodies in several disease situations that commonly occur in patients with suspected or documented systemic rheumatic diseases. Emphasis is placed on the use of these tests only in situations in which the test results can be expected to provide information necessary for clinical decision making. Those tests of limited medical usefulness and situations in which test results are likely to be misleading are also identified. (Arch Pathol Lab Med. 2000;124:71‐81)
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guidelines for clinical use of the antiNuclear antibody test and tests for specific autoantibodies to Nuclear Antigens american college of pathologists
Archives of Pathology & Laboratory Medicine, 2000Co-Authors: A Kavanaugh, Russell H Tomar, John D Reveille, Daniel H Solomon, Henry A HomburgerAbstract:The following guideline presents a series of recommendations based on published medical literature for use of the antiNuclear antibody (ANA) test and tests for specific autoantibodies to Nuclear Antigens in the diagnostic evaluation, prognostic assessment, and monitoring of patients with systemic rheumatic diseases. The guideline emphasizes the need for clinical evaluation to improve the usefulness of test results in patient management. Consideration is given to appropriate use of the generic ANA test in the initial evaluation of patients with signs and symptoms of a systemic rheumatic disease, the evaluation of patients suspected of having lupus erythematosus, use in clinical situations in which the ANA test is required to establish a disease diagnosis, and identification of clinical situations in which the ANA test has little value. Sections are also devoted to recommendations aimed at improving the analytic methods used to detect and measure ANA and specific autoantibodies to Nuclear Antigens and to the appropriate use of tests for specific autoantibodies in several disease situations that commonly occur in patients with suspected or documented systemic rheumatic diseases. Emphasis is placed on the use of these tests only in situations in which the test results can be expected to provide information necessary for clinical decision making. Those tests of limited medical usefulness and situations in which test results are likely to be misleading are also identified.
Hyon Suk Kim - One of the best experts on this subject based on the ideXlab platform.
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detection of anti extractable Nuclear Antigens in patients with systemic rheumatic disease via fluorescence enzyme immunoassay and its clinical utility
Yonsei Medical Journal, 2020Co-Authors: Younhee Park, Kyung A Lee, Hyon Suk KimAbstract:PURPOSE Testing for autoantibodies to extractable Nuclear Antigens (ENAs) plays an important role in the diagnosis and management of systemic rheumatic disease. Currently, no gold standard tests are available for detecting anti-ENAs. To address this gap, we aimed to identify an assay that exhibits satisfactory diagnostic performance in the detection of five common anti-ENAs by comparing two commonly used assays, an automated fluorescent enzyme immunoassay (FEIA) and a microplate ELISA assay. MATERIALS AND METHODS Sera from 100 patients with systemic rheumatic disease were collected and assayed with FEIA and microplate ELISA to detect anti-ENAs. Statistical analyses were performed to check the agreement rate between the two platforms using kappa coefficients. Analytical sensitivity and specificity for each assay were calculated. RESULTS The concordance rates between ELISA and FEIA ranged from 89% for anti-RNP to 97% for anti-Scl-70, and the kappa coefficients of the two assays were in the range of 0.44 to 0.82. Between the two assays, a significant difference in sensitivity and specificity was seen only for anti-Sm and anti-RNP, respectively. CONCLUSION In this study, FEIA and ELISA showed comparable efficiency for detecting anti-ENAs.
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comparison of automated multiplexed bead based ana screening assay with elisa for detecting five common anti extractable Nuclear Antigens and anti dsdna in systemic rheumatic diseases
Clinica Chimica Acta, 2012Co-Authors: Yoonjung Kim, Yongjung Park, Eun Young Lee, Hyon Suk KimAbstract:Abstract Background A newly developed and totally automated Luminex-based assay, the BioPlex™ 2200 system, is able to detect various autoantibodies simultaneously from a single sample. We compared the BioPlex™ 2200 system with ELISA for the detection of six autoantibodies. Methods A total of 127 serum samples from the patients with systemic rheumatic diseases were collected and assayed with the BioPlex™ 2200 system (Bio-Rad, USA) and conventional ELISA (INOVA Diagnostics, USA) for 5 anti-extractable Nuclear Antigens. Additionally, relative sensitivity of the BioPlex™ 2200 system for detecting anti-dsDNA was evaluated with 79 specimens from SLE patients, which were positive for anti-dsDNA by ELISA. Results The concordance rates between ELISA and the BioPlex ranged from 88.1% for anti-RNP to 95.2% for anti-Scl-70, and the kappa coefficients between the results by the two assays were from 0.48 to 0.67. Among the 79 anti-dsDNA positive specimens by ELISA, seventy-eight (98.7%) showed positive results for anti-dsDNA by the BioPlex. Conclusions The BioPlex™ 2200 system showed comparable results with those by conventional ELISA for detecting autoantibodies, and this automated assay could measure multifarious autoantibodies concurrently in a single sample. It could be effectively used in clinical laboratories for screening autoimmune diseases.
Philip J Titcombe - One of the best experts on this subject based on the ideXlab platform.
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differential acpa binding to Nuclear Antigens reveals a pad independent pathway and a distinct subset of acetylation cross reactive autoantibodies in rheumatoid arthritis
Frontiers in Immunology, 2019Co-Authors: Katy A Lloyd, Peter Sahlstrom, Johanna Steen, Philip J Titcombe, Gustaf Wigerblad, Karine Chemin, Manasa G GarimellaAbstract:Rheumatoid arthritis (RA) associated anti-citrullinated protein autoantibodies (ACPA) target a wide range of modified proteins. Citrullination occurs during physiological processes such as apoptosis, yet little is known about the interaction of ACPA with Nuclear Antigens or apoptotic cells. Since uncleared apoptotic cells and neutrophil extracellular trap (NET) products have been postulated to be central sources of autoantigen and immunostimulation in autoimmune disease, we sought to characterize the anti-Nuclear and anti-neutrophil reactivities of ACPA. Serology showed that a subset of anti-CCP2 seropositive RA patients had high reactivity to full-length citrullinated histones. In contrast, seronegative RA patients displayed elevated IgG reactivity to native histone compared to controls, but no citrulline-specific reactivity. Screening of 10 single B-cell derived monoclonal ACPA from RA patients revealed that four ACPA exhibited strong binding to apoptotic cells and three of these had anti-Nuclear (ANA) autoantibody reactivity. Modified histones were confirmed to be the primary targets of this anti-Nuclear ACPA subset following immunoprecipitation from apoptotic cell lysates. Monoclonal ACPA were also screened for reactivities against stimulated murine and human neutrophils, and all the Nuclear-reactive monoclonal ACPA bound to NETs. Intriguingly, one ACPA mAb displayed a contrasting cytoplasmic periNuclear neutrophil binding and may represent a different NET-reactive ACPA subset. Notably, studies of CRISPR-Cas9 PAD4 KO cells and cells from PAD KO mice showed that the cytoplasmic NET-binding was fully dependent on PAD4, whilst Nuclear- and histone-mediated NET reactivity was largely PAD-independent. Our further analysis revealed that the Nuclear binding could be explained by consensus-motif driven ACPA cross-reactivity to acetylated histones. Specific acetylated histone peptides targeted by the monoclonal antibodies were identified and the anti-modified protein autoantibody (AMPA) profile of the ACPA was found to correlate with the functional activity of the antibodies. In conclusion, when investigating monoclonal ACPA, we could group ACPA into distinct subsets based on their Nuclear binding-patterns and acetylation-mediated binding to apoptotic cells, neutrophils, and NETs. Differential anti-modified protein reactivities of RA-autoantibody subsets could have an important functional impact and provide insights in RA pathogenesis.
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Data_Sheet_1_Differential ACPA Binding to Nuclear Antigens Reveals a PAD-Independent Pathway and a Distinct Subset of Acetylation Cross-Reactive Autoantibodies in Rheumatoid Arthritis.PDF
2019Co-Authors: Katy A Lloyd, Peter Sahlstrom, Johanna Steen, Philip J Titcombe, Diana Zhou, Gustaf Wigerblad, Karine Chemin, Bianka Marklein, Manasa G Garimella, Ragnhild StalesenAbstract:Rheumatoid arthritis (RA) associated anti-citrullinated protein autoantibodies (ACPA) target a wide range of modified proteins. Citrullination occurs during physiological processes such as apoptosis, yet little is known about the interaction of ACPA with Nuclear Antigens or apoptotic cells. Since uncleared apoptotic cells and neutrophil extracellular trap (NET) products have been postulated to be central sources of autoantigen and immunostimulation in autoimmune disease, we sought to characterize the anti-Nuclear and anti-neutrophil reactivities of ACPA. Serology showed that a subset of anti-CCP2 seropositive RA patients had high reactivity to full-length citrullinated histones. In contrast, seronegative RA patients displayed elevated IgG reactivity to native histone compared to controls, but no citrulline-specific reactivity. Screening of 10 single B-cell derived monoclonal ACPA from RA patients revealed that four ACPA exhibited strong binding to apoptotic cells and three of these had anti-Nuclear (ANA) autoantibody reactivity. Modified histones were confirmed to be the primary targets of this anti-Nuclear ACPA subset following immunoprecipitation from apoptotic cell lysates. Monoclonal ACPA were also screened for reactivities against stimulated murine and human neutrophils, and all the Nuclear-reactive monoclonal ACPA bound to NETs. Intriguingly, one ACPA mAb displayed a contrasting cytoplasmic periNuclear neutrophil binding and may represent a different NET-reactive ACPA subset. Notably, studies of CRISPR-Cas9 PAD4 KO cells and cells from PAD KO mice showed that the cytoplasmic NET-binding was fully dependent on PAD4, whilst Nuclear- and histone-mediated NET reactivity was largely PAD-independent. Our further analysis revealed that the Nuclear binding could be explained by consensus-motif driven ACPA cross-reactivity to acetylated histones. Specific acetylated histone peptides targeted by the monoclonal antibodies were identified and the anti-modified protein autoantibody (AMPA) profile of the ACPA was found to correlate with the functional activity of the antibodies. In conclusion, when investigating monoclonal ACPA, we could group ACPA into distinct subsets based on their Nuclear binding-patterns and acetylation-mediated binding to apoptotic cells, neutrophils, and NETs. Differential anti-modified protein reactivities of RA-autoantibody subsets could have an important functional impact and provide insights in RA pathogenesis.
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pad4 independent interaction of acpa with Nuclear Antigens in apoptotic cells and neutrophil extracellular traps nets defines a subset of autoantibodies
Arthritis & Rheumatism, 2018Co-Authors: Gustaf Wigerblad, Katy A Lloyd, Peter Sahlstrom, Johanna Steen, Philip J Titcombe, Diana Zhou, Karine Chemin, Ragnhild Stalesen, Bianka Marklein, Elena OssipovaAbstract:PAD4-Independent Interaction of ACPA with Nuclear Antigens in Apoptotic Cells and Neutrophil Extracellular Traps (NETs) Defines a Subset of Autoantibodies
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novel interaction between anti citrulline monoclonal antibodies and apoptotic cells is mediated through citrullinated Nuclear Antigens
Arthritis & Rheumatism, 2017Co-Authors: Katy A Lloyd, Peter Sahlstrom, Johanna Steen, Philip J Titcombe, Diana Zhou, Christina Lundqvist, Olov Ekwall, Jimmy Ytterberg, Johan Ronnelid, Daniel L MuellerAbstract:Novel Interaction between Anti-Citrulline Monoclonal Antibodies and Apoptotic Cells Is Mediated through Citrullinated Nuclear Antigens
