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Chester V Oddis - One of the best experts on this subject based on the ideXlab platform.
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osteolytic change of distal interphalangeal Joints and sacroiliac Joints in subluxing arthropathy associated with anti Jo 1 Antibody
Joint Bone Spine, 2013Co-Authors: Yuko Kaneko, Masataka Kuwana, Tsutomu Takeuchi, Chester V OddisAbstract:Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 31 juillet 2013
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characterization and peripheral blood biomarker assessment of anti Jo 1 Antibody positive interstitial lung disease
Arthritis & Rheumatism, 2009Co-Authors: Thomas J Richards, Aaron Eggebeen, Samuel Yousem, Bernadette R. Gochuico, N. Fertig, Naftali Kaminski, Claire Fuhrman, Chester V Oddis, Kevin F Gibson, Ivan O. RosasAbstract:Objective Using a combination of clinical, radiographic, functional, and serum protein biomarker assessments, this study was aimed at defining the prevalence and clinical characteristics of interstitial lung disease (ILD) in a large cohort of patients with anti–Jo-1 antibodies. Methods A review of clinical records, pulmonary function test results, and findings on imaging studies determined the existence of ILD in anti–Jo-1 Antibody–positive individuals whose data were accumulated in the University of Pittsburgh Myositis Database from 1982 to 2007. Multiplex enzyme-linked immunosorbent assays (ELISAs) for serum inflammation markers, cytokines, chemokines, and matrix metalloproteinases in different patient subgroups were performed to assess the serum proteins associated with anti–Jo-1 Antibody–positive ILD. Results Among the 90 anti–Jo-1 Antibody–positive individuals with sufficient clinical, radiographic, and/or pulmonary function data, 77 (86%) met the criteria for ILD. While computed tomography scans revealed a variety of patterns suggestive of underlying usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia, a review of the histopathologic abnormalities in a subset of patients undergoing open lung biopsy or transplantation or whose lung tissue was obtained at autopsy (n = 22) demonstrated a preponderance of UIP and diffuse alveolar damage. Analysis by multiplex ELISA yielded statistically significant associations between anti–Jo-1 Antibody–positive ILD and elevated serum levels of C-reactive protein (CRP), CXCL9, and CXCL10, which distinguished this disease entity from idiopathic pulmonary fibrosis and anti–signal recognition particle Antibody–positive myositis. Recursive partitioning further demonstrated that combinations of these and other serum protein biomarkers can distinguish these disease subgroups at high levels of sensitivity and specificity. Conclusion In this large cohort of anti–Jo-1 Antibody–positive individuals, the incidence of ILD approached 90%. Multiplex ELISA demonstrated disease-specific associations between anti–Jo-1 Antibody–positive ILD and serum levels of CRP as well as the interferon-γ–inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD.
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Characterization and peripheral blood biomarker assessment of anti–Jo-1 Antibody–positive interstitial lung disease
Arthritis & Rheumatism, 2009Co-Authors: Thomas J Richards, Aaron Eggebeen, Samuel Yousem, Bernadette R. Gochuico, N. Fertig, Naftali Kaminski, Claire Fuhrman, Chester V Oddis, Kevin F Gibson, Ivan O. RosasAbstract:Objective Using a combination of clinical, radiographic, functional, and serum protein biomarker assessments, this study was aimed at defining the prevalence and clinical characteristics of interstitial lung disease (ILD) in a large cohort of patients with anti–Jo-1 antibodies. Methods A review of clinical records, pulmonary function test results, and findings on imaging studies determined the existence of ILD in anti–Jo-1 Antibody–positive individuals whose data were accumulated in the University of Pittsburgh Myositis Database from 1982 to 2007. Multiplex enzyme-linked immunosorbent assays (ELISAs) for serum inflammation markers, cytokines, chemokines, and matrix metalloproteinases in different patient subgroups were performed to assess the serum proteins associated with anti–Jo-1 Antibody–positive ILD. Results Among the 90 anti–Jo-1 Antibody–positive individuals with sufficient clinical, radiographic, and/or pulmonary function data, 77 (86%) met the criteria for ILD. While computed tomography scans revealed a variety of patterns suggestive of underlying usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia, a review of the histopathologic abnormalities in a subset of patients undergoing open lung biopsy or transplantation or whose lung tissue was obtained at autopsy (n = 22) demonstrated a preponderance of UIP and diffuse alveolar damage. Analysis by multiplex ELISA yielded statistically significant associations between anti–Jo-1 Antibody–positive ILD and elevated serum levels of C-reactive protein (CRP), CXCL9, and CXCL10, which distinguished this disease entity from idiopathic pulmonary fibrosis and anti–signal recognition particle Antibody–positive myositis. Recursive partitioning further demonstrated that combinations of these and other serum protein biomarkers can distinguish these disease subgroups at high levels of sensitivity and specificity. Conclusion In this large cohort of anti–Jo-1 Antibody–positive individuals, the incidence of ILD approached 90%. Multiplex ELISA demonstrated disease-specific associations between anti–Jo-1 Antibody–positive ILD and serum levels of CRP as well as the interferon-γ–inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD.
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critical requirement for professional apcs in eliciting t cell responses to novel fragments of histidyl trna synthetase Jo 1 in Jo 1 Antibody positive polymyositis
Journal of Immunology, 2002Co-Authors: Dana P Ascherman, Chester V Oddis, Timothy B Oriss, Timothy M WrightAbstract:Polymyositis (PM) is an autoimmune muscle disease characterized by oligoclonal T cell infiltrates mediating myocytotoxicity. Although antigenic triggers for this process remain undefined, clinically homogeneous subsets of PM patients are characterized by autoantibodies directed against nuclear and cytoplasmic Ags that include histidyl-tRNA synthetase (Jo-1). Available evidence suggests that formation of anti-Jo-1 autoantibodies is Ag-driven and therefore dependent on CD4+ T cells that may also direct cytolytic CD8+ T cells involved in myocyte destruction. To assess peripheral blood T cell responses to Jo-1, we first subcloned full-length human Jo-1 as well as novel fragments of Jo-1 into the maltose-binding protein expression vector pMALc2. Expressed proteins were then used in standard proliferation assays with either PBMC or autologous DCs as sources of APCs. Although PBMC-derived APCs and DCs both supported peripheral blood T cell proliferation when primed with full-length human Jo-1, only DCs promoted proliferative responses to a unique amino-terminal fragment of Jo-1. mAb blockade of different HLA Ags revealed that these responses were MHC class II dependent. Therefore, for the first time, these studies demonstrate anti-Jo-1 T cell responses in Jo-1 Ab-positive PM patients as well as in healthy control subjects. More importantly, this work underscores the critical importance of APC type in dictating T cell responses to a novel antigenic fragment of Jo-1.
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adult respiratory distress syndrome in polymyositis patients with the anti Jo 1 Antibody
Arthritis & Rheumatism, 1995Co-Authors: Kevin Clawson, Chester V OddisAbstract:: We report 3 patients with polymyositis and the anti-Jo-1 Antibody who developed fatal adult respiratory distress syndrome (ARDS). Other than the presence of the anti-Jo-1 Antibody, there were no other consistent clinical features at the onset of disease that were predictive of ARDS development.
N. Fertig - One of the best experts on this subject based on the ideXlab platform.
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hla dpb1 associations differ between drb1 03 positive anti Jo 1 and anti pm scl Antibody positive idiopathic inflammatory myopathy
Rheumatology, 2009Co-Authors: Hector Chinoy, N. Fertig, Carmine V. Oddis, Debbie Payne, Kate V Poulton, Zoe Betteridge, Harsha Gunawardena, J Davidson, Neil Mchugh, Lucy R WedderburnAbstract:OBJECTIVE: The HLA 8.1 ancestral haplotype (HLA-B*08/DRB1*03/DQA1*05/DQB1*02) is associated with adult/juvenile idiopathic inflammatory myopathy (IIM), but confers a greater strength of association in patients possessing anti-Jo-1 or anti-PM-Scl antibodies. The HLA-DPB1 gene is centromeric to other HLA class II loci and separated by a recombination hotspot. We investigated whether HLA-DPB1 associations differ between anti-Jo-1 and anti-PM-Scl Antibody-positive IIM cases. METHODS: Two hundred and thirty-three adult IIM patients (73% females, 49.4 +/- 13.6 years) with PM (n = 89), DM (n = 88) and myositis associated with another CTD (n = 55) and 85 juvenile DM patients (75% females, 6.2 +/- 3.6 years) were compared with 678 UK Caucasian controls. Patients/controls were genotyped for HLA-DPB1 and DRB1 alleles. Myositis-specific and associated antibodies were identified in cases using immunoprecipitation. RESULTS: HLA-DPB1*0101 was associated with IIM overall [22 vs 13% controls, corrected probability (P(corr)) = 2 x 10(-03); odds ratio (OR) 2.0; 95% CI 1.4, 2.9], PM (P(corr) = 7 x 10(-03); OR 2.5; 95% CI 1.5, 4.4) and anti-Jo-1 (P(corr) = 3 x 10(-5); OR 4.1; 95% CI 2.1, 7.8). No significant DPB1*0101 difference was present between anti-PM-Scl cases and controls. The HLA-DPB1*0101 association in IIM overall cases was dependent on the presence of DRB1*03. A number of HLA-DRB1*03/DPB1 haplotypes were identified, but only DRB1*03/DPB1*0101 was associated with anti-Jo-1 Antibody-positive cases. CONCLUSIONS: The HLA-DRB1*03/DPB1*0101 haplotype is a risk factor for anti-Jo-1 Antibody-positive IIM. Thus, although DRB1*03 is strongly associated with possession of either anti-Jo-1 or anti-PM-Scl, differing Antibody associations are observed at the HLA-DPB1 locus.
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characterization and peripheral blood biomarker assessment of anti Jo 1 Antibody positive interstitial lung disease
Arthritis & Rheumatism, 2009Co-Authors: Thomas J Richards, Aaron Eggebeen, Samuel Yousem, Bernadette R. Gochuico, N. Fertig, Naftali Kaminski, Claire Fuhrman, Chester V Oddis, Kevin F Gibson, Ivan O. RosasAbstract:Objective Using a combination of clinical, radiographic, functional, and serum protein biomarker assessments, this study was aimed at defining the prevalence and clinical characteristics of interstitial lung disease (ILD) in a large cohort of patients with anti–Jo-1 antibodies. Methods A review of clinical records, pulmonary function test results, and findings on imaging studies determined the existence of ILD in anti–Jo-1 Antibody–positive individuals whose data were accumulated in the University of Pittsburgh Myositis Database from 1982 to 2007. Multiplex enzyme-linked immunosorbent assays (ELISAs) for serum inflammation markers, cytokines, chemokines, and matrix metalloproteinases in different patient subgroups were performed to assess the serum proteins associated with anti–Jo-1 Antibody–positive ILD. Results Among the 90 anti–Jo-1 Antibody–positive individuals with sufficient clinical, radiographic, and/or pulmonary function data, 77 (86%) met the criteria for ILD. While computed tomography scans revealed a variety of patterns suggestive of underlying usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia, a review of the histopathologic abnormalities in a subset of patients undergoing open lung biopsy or transplantation or whose lung tissue was obtained at autopsy (n = 22) demonstrated a preponderance of UIP and diffuse alveolar damage. Analysis by multiplex ELISA yielded statistically significant associations between anti–Jo-1 Antibody–positive ILD and elevated serum levels of C-reactive protein (CRP), CXCL9, and CXCL10, which distinguished this disease entity from idiopathic pulmonary fibrosis and anti–signal recognition particle Antibody–positive myositis. Recursive partitioning further demonstrated that combinations of these and other serum protein biomarkers can distinguish these disease subgroups at high levels of sensitivity and specificity. Conclusion In this large cohort of anti–Jo-1 Antibody–positive individuals, the incidence of ILD approached 90%. Multiplex ELISA demonstrated disease-specific associations between anti–Jo-1 Antibody–positive ILD and serum levels of CRP as well as the interferon-γ–inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD.
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Characterization and peripheral blood biomarker assessment of anti–Jo-1 Antibody–positive interstitial lung disease
Arthritis & Rheumatism, 2009Co-Authors: Thomas J Richards, Aaron Eggebeen, Samuel Yousem, Bernadette R. Gochuico, N. Fertig, Naftali Kaminski, Claire Fuhrman, Chester V Oddis, Kevin F Gibson, Ivan O. RosasAbstract:Objective Using a combination of clinical, radiographic, functional, and serum protein biomarker assessments, this study was aimed at defining the prevalence and clinical characteristics of interstitial lung disease (ILD) in a large cohort of patients with anti–Jo-1 antibodies. Methods A review of clinical records, pulmonary function test results, and findings on imaging studies determined the existence of ILD in anti–Jo-1 Antibody–positive individuals whose data were accumulated in the University of Pittsburgh Myositis Database from 1982 to 2007. Multiplex enzyme-linked immunosorbent assays (ELISAs) for serum inflammation markers, cytokines, chemokines, and matrix metalloproteinases in different patient subgroups were performed to assess the serum proteins associated with anti–Jo-1 Antibody–positive ILD. Results Among the 90 anti–Jo-1 Antibody–positive individuals with sufficient clinical, radiographic, and/or pulmonary function data, 77 (86%) met the criteria for ILD. While computed tomography scans revealed a variety of patterns suggestive of underlying usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia, a review of the histopathologic abnormalities in a subset of patients undergoing open lung biopsy or transplantation or whose lung tissue was obtained at autopsy (n = 22) demonstrated a preponderance of UIP and diffuse alveolar damage. Analysis by multiplex ELISA yielded statistically significant associations between anti–Jo-1 Antibody–positive ILD and elevated serum levels of C-reactive protein (CRP), CXCL9, and CXCL10, which distinguished this disease entity from idiopathic pulmonary fibrosis and anti–signal recognition particle Antibody–positive myositis. Recursive partitioning further demonstrated that combinations of these and other serum protein biomarkers can distinguish these disease subgroups at high levels of sensitivity and specificity. Conclusion In this large cohort of anti–Jo-1 Antibody–positive individuals, the incidence of ILD approached 90%. Multiplex ELISA demonstrated disease-specific associations between anti–Jo-1 Antibody–positive ILD and serum levels of CRP as well as the interferon-γ–inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD.
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Characterization and peripheral blood biomarker assessment of anti-Jo-1 Antibody-positive interstitial lung disease
Arthritis and Rheumatism, 2009Co-Authors: Thomas J Richards, Aaron Eggebeen, Kevin Gibson, Samuel Yousem, Bernadette R. Gochuico, N. Fertig, Naftali Kaminski, Claire Fuhrman, Carmine V. Oddis, Ivan O. RosasAbstract:OBJECTIVE: Using a combination of clinical, radiographic, functional, and serum protein biomarker assessments, this study was aimed at defining the prevalence and clinical characteristics of interstitial lung disease (ILD) in a large cohort of patients with anti-Jo-1 antibodies. METHODS: A review of clinical records, pulmonary function test results, and findings on imaging studies determined the existence of ILD in anti-Jo-1 Antibody-positive individuals whose data were accumulated in the University of Pittsburgh Myositis Database from 1982 to 2007. Multiplex enzyme-linked immunosorbent assays (ELISAs) for serum inflammation markers, cytokines, chemokines, and matrix metalloproteinases in different patient subgroups were performed to assess the serum proteins associated with anti-Jo-1 Antibody-positive ILD. RESULTS: Among the 90 anti-Jo-1 Antibody-positive individuals with sufficient clinical, radiographic, and/or pulmonary function data, 77 (86%) met the criteria for ILD. While computed tomography scans revealed a variety of patterns suggestive of underlying usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia, a review of the histopathologic abnormalities in a subset of patients undergoing open lung biopsy or transplantation or whose lung tissue was obtained at autopsy (n = 22) demonstrated a preponderance of UIP and diffuse alveolar damage. Analysis by multiplex ELISA yielded statistically significant associations between anti-Jo-1 Antibody-positive ILD and elevated serum levels of C-reactive protein (CRP), CXCL9, and CXCL10, which distinguished this disease entity from idiopathic pulmonary fibrosis and anti-signal recognition particle Antibody-positive myositis. Recursive partitioning further demonstrated that combinations of these and other serum protein biomarkers can distinguish these disease subgroups at high levels of sensitivity and specificity. CONCLUSION: In this large cohort of anti-Jo-1 Antibody-positive individuals, the incidence of ILD approached 90%. Multiplex ELISA demonstrated disease-specific associations between anti-Jo-1 Antibody-positive ILD and serum levels of CRP as well as the interferon-gamma-inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD.
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anti Jo 1 Antibody levels correlate with disease activity in idiopathic inflammatory myopathy
Arthritis & Rheumatism, 2007Co-Authors: Kerry B Stone, N. Fertig, Carmine V. Oddis, Yasuhiro Katsumata, Mary Lucas, Molly T Vogt, Robyn T Domsic, Dana P AschermanAbstract:Objective Previous case series have examined the relationship between anti–Jo-1 Antibody levels and myositis disease activity, demonstrating equivocal results. Using enzyme-linked immunosorbent assays (ELISAs) and novel measures of myositis disease activity, the current study was undertaken to systematically reexamine the association between anti–Jo-1 Antibody levels and various disease manifestations of myositis. Methods Serum anti–Jo-1 Antibody levels were quantified using 2 independent ELISA methods, while disease activity was retrospectively graded using the Myositis Disease Activity Assessment Tool, which measures disease activity in 7 different organ systems via the Myositis Disease Activity Assessment Visual Analog Scale (VAS) and the Myositis Intention-to-Treat Index (MITAX) components. Spearman's rank correlation coefficients and mixed linear regression analysis were used to identify associations between anti–Jo-1 Antibody levels and organ-specific disease activity in cross-sectional and longitudinal analyses, respectively. Results Cross-sectional assessment of 81 patients with anti–Jo-1 Antibody revealed a modest correlation between the anti–Jo-1 Antibody level and the serum creatine kinase (CK) level, as well as muscle and Joint disease activity. Correlation coefficients were similar for CK levels (rs = 0.38, P = 0.002), myositis VAS (rs = 0.36, P = 0.002), and arthritis VAS (rs = 0.40, P = 0.001). In multiple regression analyses of 11 patients with serial samples, anti–Jo-1 Antibody levels correlated significantly with CK levels (R2 = 0.65, P = 0.0002), myositis VAS (R2 = 0.53, P = 0.0008), arthritis VAS (R2 = 0.53, P = 0.006), pulmonary VAS (R2 = 0.69, P = 0.005), global VAS (R2 = 0.63, P = 0.002), and global MITAX (R2 = 0.64, P = 0.0003). Conclusion In this large series of patients with idiopathic inflammatory myopathy, anti–Jo-1 Antibody levels correlated modestly with muscle and Joint disease, an association confirmed by a custom ELISA using recombinant human Jo-1. More striking associations emerged in a smaller longitudinal subset of patients that link anti–Jo-1 Antibody levels to muscle, Joint, lung, and global disease activity.
Ivan O. Rosas - One of the best experts on this subject based on the ideXlab platform.
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Characterization and peripheral blood biomarker assessment of anti–Jo-1 Antibody–positive interstitial lung disease
Arthritis & Rheumatism, 2009Co-Authors: Thomas J Richards, Aaron Eggebeen, Samuel Yousem, Bernadette R. Gochuico, N. Fertig, Naftali Kaminski, Claire Fuhrman, Chester V Oddis, Kevin F Gibson, Ivan O. RosasAbstract:Objective Using a combination of clinical, radiographic, functional, and serum protein biomarker assessments, this study was aimed at defining the prevalence and clinical characteristics of interstitial lung disease (ILD) in a large cohort of patients with anti–Jo-1 antibodies. Methods A review of clinical records, pulmonary function test results, and findings on imaging studies determined the existence of ILD in anti–Jo-1 Antibody–positive individuals whose data were accumulated in the University of Pittsburgh Myositis Database from 1982 to 2007. Multiplex enzyme-linked immunosorbent assays (ELISAs) for serum inflammation markers, cytokines, chemokines, and matrix metalloproteinases in different patient subgroups were performed to assess the serum proteins associated with anti–Jo-1 Antibody–positive ILD. Results Among the 90 anti–Jo-1 Antibody–positive individuals with sufficient clinical, radiographic, and/or pulmonary function data, 77 (86%) met the criteria for ILD. While computed tomography scans revealed a variety of patterns suggestive of underlying usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia, a review of the histopathologic abnormalities in a subset of patients undergoing open lung biopsy or transplantation or whose lung tissue was obtained at autopsy (n = 22) demonstrated a preponderance of UIP and diffuse alveolar damage. Analysis by multiplex ELISA yielded statistically significant associations between anti–Jo-1 Antibody–positive ILD and elevated serum levels of C-reactive protein (CRP), CXCL9, and CXCL10, which distinguished this disease entity from idiopathic pulmonary fibrosis and anti–signal recognition particle Antibody–positive myositis. Recursive partitioning further demonstrated that combinations of these and other serum protein biomarkers can distinguish these disease subgroups at high levels of sensitivity and specificity. Conclusion In this large cohort of anti–Jo-1 Antibody–positive individuals, the incidence of ILD approached 90%. Multiplex ELISA demonstrated disease-specific associations between anti–Jo-1 Antibody–positive ILD and serum levels of CRP as well as the interferon-γ–inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD.
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characterization and peripheral blood biomarker assessment of anti Jo 1 Antibody positive interstitial lung disease
Arthritis & Rheumatism, 2009Co-Authors: Thomas J Richards, Aaron Eggebeen, Samuel Yousem, Bernadette R. Gochuico, N. Fertig, Naftali Kaminski, Claire Fuhrman, Chester V Oddis, Kevin F Gibson, Ivan O. RosasAbstract:Objective Using a combination of clinical, radiographic, functional, and serum protein biomarker assessments, this study was aimed at defining the prevalence and clinical characteristics of interstitial lung disease (ILD) in a large cohort of patients with anti–Jo-1 antibodies. Methods A review of clinical records, pulmonary function test results, and findings on imaging studies determined the existence of ILD in anti–Jo-1 Antibody–positive individuals whose data were accumulated in the University of Pittsburgh Myositis Database from 1982 to 2007. Multiplex enzyme-linked immunosorbent assays (ELISAs) for serum inflammation markers, cytokines, chemokines, and matrix metalloproteinases in different patient subgroups were performed to assess the serum proteins associated with anti–Jo-1 Antibody–positive ILD. Results Among the 90 anti–Jo-1 Antibody–positive individuals with sufficient clinical, radiographic, and/or pulmonary function data, 77 (86%) met the criteria for ILD. While computed tomography scans revealed a variety of patterns suggestive of underlying usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia, a review of the histopathologic abnormalities in a subset of patients undergoing open lung biopsy or transplantation or whose lung tissue was obtained at autopsy (n = 22) demonstrated a preponderance of UIP and diffuse alveolar damage. Analysis by multiplex ELISA yielded statistically significant associations between anti–Jo-1 Antibody–positive ILD and elevated serum levels of C-reactive protein (CRP), CXCL9, and CXCL10, which distinguished this disease entity from idiopathic pulmonary fibrosis and anti–signal recognition particle Antibody–positive myositis. Recursive partitioning further demonstrated that combinations of these and other serum protein biomarkers can distinguish these disease subgroups at high levels of sensitivity and specificity. Conclusion In this large cohort of anti–Jo-1 Antibody–positive individuals, the incidence of ILD approached 90%. Multiplex ELISA demonstrated disease-specific associations between anti–Jo-1 Antibody–positive ILD and serum levels of CRP as well as the interferon-γ–inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD.
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Characterization and peripheral blood biomarker assessment of anti-Jo-1 Antibody-positive interstitial lung disease
Arthritis and Rheumatism, 2009Co-Authors: Thomas J Richards, Aaron Eggebeen, Kevin Gibson, Samuel Yousem, Bernadette R. Gochuico, N. Fertig, Naftali Kaminski, Claire Fuhrman, Carmine V. Oddis, Ivan O. RosasAbstract:OBJECTIVE: Using a combination of clinical, radiographic, functional, and serum protein biomarker assessments, this study was aimed at defining the prevalence and clinical characteristics of interstitial lung disease (ILD) in a large cohort of patients with anti-Jo-1 antibodies. METHODS: A review of clinical records, pulmonary function test results, and findings on imaging studies determined the existence of ILD in anti-Jo-1 Antibody-positive individuals whose data were accumulated in the University of Pittsburgh Myositis Database from 1982 to 2007. Multiplex enzyme-linked immunosorbent assays (ELISAs) for serum inflammation markers, cytokines, chemokines, and matrix metalloproteinases in different patient subgroups were performed to assess the serum proteins associated with anti-Jo-1 Antibody-positive ILD. RESULTS: Among the 90 anti-Jo-1 Antibody-positive individuals with sufficient clinical, radiographic, and/or pulmonary function data, 77 (86%) met the criteria for ILD. While computed tomography scans revealed a variety of patterns suggestive of underlying usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia, a review of the histopathologic abnormalities in a subset of patients undergoing open lung biopsy or transplantation or whose lung tissue was obtained at autopsy (n = 22) demonstrated a preponderance of UIP and diffuse alveolar damage. Analysis by multiplex ELISA yielded statistically significant associations between anti-Jo-1 Antibody-positive ILD and elevated serum levels of C-reactive protein (CRP), CXCL9, and CXCL10, which distinguished this disease entity from idiopathic pulmonary fibrosis and anti-signal recognition particle Antibody-positive myositis. Recursive partitioning further demonstrated that combinations of these and other serum protein biomarkers can distinguish these disease subgroups at high levels of sensitivity and specificity. CONCLUSION: In this large cohort of anti-Jo-1 Antibody-positive individuals, the incidence of ILD approached 90%. Multiplex ELISA demonstrated disease-specific associations between anti-Jo-1 Antibody-positive ILD and serum levels of CRP as well as the interferon-gamma-inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD.
Dana P Ascherman - One of the best experts on this subject based on the ideXlab platform.
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anti Jo 1 Antibody levels correlate with disease activity in idiopathic inflammatory myopathy
Arthritis & Rheumatism, 2007Co-Authors: Kerry B Stone, N. Fertig, Carmine V. Oddis, Yasuhiro Katsumata, Mary Lucas, Molly T Vogt, Robyn T Domsic, Dana P AschermanAbstract:Objective Previous case series have examined the relationship between anti–Jo-1 Antibody levels and myositis disease activity, demonstrating equivocal results. Using enzyme-linked immunosorbent assays (ELISAs) and novel measures of myositis disease activity, the current study was undertaken to systematically reexamine the association between anti–Jo-1 Antibody levels and various disease manifestations of myositis. Methods Serum anti–Jo-1 Antibody levels were quantified using 2 independent ELISA methods, while disease activity was retrospectively graded using the Myositis Disease Activity Assessment Tool, which measures disease activity in 7 different organ systems via the Myositis Disease Activity Assessment Visual Analog Scale (VAS) and the Myositis Intention-to-Treat Index (MITAX) components. Spearman's rank correlation coefficients and mixed linear regression analysis were used to identify associations between anti–Jo-1 Antibody levels and organ-specific disease activity in cross-sectional and longitudinal analyses, respectively. Results Cross-sectional assessment of 81 patients with anti–Jo-1 Antibody revealed a modest correlation between the anti–Jo-1 Antibody level and the serum creatine kinase (CK) level, as well as muscle and Joint disease activity. Correlation coefficients were similar for CK levels (rs = 0.38, P = 0.002), myositis VAS (rs = 0.36, P = 0.002), and arthritis VAS (rs = 0.40, P = 0.001). In multiple regression analyses of 11 patients with serial samples, anti–Jo-1 Antibody levels correlated significantly with CK levels (R2 = 0.65, P = 0.0002), myositis VAS (R2 = 0.53, P = 0.0008), arthritis VAS (R2 = 0.53, P = 0.006), pulmonary VAS (R2 = 0.69, P = 0.005), global VAS (R2 = 0.63, P = 0.002), and global MITAX (R2 = 0.64, P = 0.0003). Conclusion In this large series of patients with idiopathic inflammatory myopathy, anti–Jo-1 Antibody levels correlated modestly with muscle and Joint disease, an association confirmed by a custom ELISA using recombinant human Jo-1. More striking associations emerged in a smaller longitudinal subset of patients that link anti–Jo-1 Antibody levels to muscle, Joint, lung, and global disease activity.
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The role of Jo-1 in the immunopathogenesis of polymyositis: Current hypotheses
Current Rheumatology Reports, 2003Co-Authors: Dana P AschermanAbstract:Polymyositis represents an autoimmune disease in which T cells mediate destruction of muscle cells. Although the precise trigger(s) for this process remain unknown, distinct clinical subsets exist that are characterized by antibodies directed against specific nuclear and cytoplasmic antigens including Jo-1 (histidyl-transfer RNA synthetase). Coupled with a range of genetic and histomorphologic data, the stereotypical serologic response suggests that antigen-specific T cells directed against Jo-1 can promote T cell-mediated cytolysis of muscle cells as well as anti-Jo-1 Antibody formation in selected patients with polymyositis. Beyond a previously developed animal model that has demonstrated the capacity of Jo-1 to promote humoral and cell-mediated immune responses leading to myositis, recent studies have revealed the existence of Jo-1-specific T cells in the peripheral blood of patients with Jo-1 Antibody-positive polymyositis. Even more striking, investigators have discovered that Jo-1 can serve as a chemokine for immature dendritic cells and T lymphocytes. Collectively, these findings suggest a mechanism by which Jo-1 can bridge the innate and adaptive immune responses, leading to the breakdown of tolerance and autoimmune destruction of muscle.
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critical requirement for professional apcs in eliciting t cell responses to novel fragments of histidyl trna synthetase Jo 1 in Jo 1 Antibody positive polymyositis
Journal of Immunology, 2002Co-Authors: Dana P Ascherman, Chester V Oddis, Timothy B Oriss, Timothy M WrightAbstract:Polymyositis (PM) is an autoimmune muscle disease characterized by oligoclonal T cell infiltrates mediating myocytotoxicity. Although antigenic triggers for this process remain undefined, clinically homogeneous subsets of PM patients are characterized by autoantibodies directed against nuclear and cytoplasmic Ags that include histidyl-tRNA synthetase (Jo-1). Available evidence suggests that formation of anti-Jo-1 autoantibodies is Ag-driven and therefore dependent on CD4+ T cells that may also direct cytolytic CD8+ T cells involved in myocyte destruction. To assess peripheral blood T cell responses to Jo-1, we first subcloned full-length human Jo-1 as well as novel fragments of Jo-1 into the maltose-binding protein expression vector pMALc2. Expressed proteins were then used in standard proliferation assays with either PBMC or autologous DCs as sources of APCs. Although PBMC-derived APCs and DCs both supported peripheral blood T cell proliferation when primed with full-length human Jo-1, only DCs promoted proliferative responses to a unique amino-terminal fragment of Jo-1. mAb blockade of different HLA Ags revealed that these responses were MHC class II dependent. Therefore, for the first time, these studies demonstrate anti-Jo-1 T cell responses in Jo-1 Ab-positive PM patients as well as in healthy control subjects. More importantly, this work underscores the critical importance of APC type in dictating T cell responses to a novel antigenic fragment of Jo-1.
Carmine V. Oddis - One of the best experts on this subject based on the ideXlab platform.
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hla dpb1 associations differ between drb1 03 positive anti Jo 1 and anti pm scl Antibody positive idiopathic inflammatory myopathy
Rheumatology, 2009Co-Authors: Hector Chinoy, N. Fertig, Carmine V. Oddis, Debbie Payne, Kate V Poulton, Zoe Betteridge, Harsha Gunawardena, J Davidson, Neil Mchugh, Lucy R WedderburnAbstract:OBJECTIVE: The HLA 8.1 ancestral haplotype (HLA-B*08/DRB1*03/DQA1*05/DQB1*02) is associated with adult/juvenile idiopathic inflammatory myopathy (IIM), but confers a greater strength of association in patients possessing anti-Jo-1 or anti-PM-Scl antibodies. The HLA-DPB1 gene is centromeric to other HLA class II loci and separated by a recombination hotspot. We investigated whether HLA-DPB1 associations differ between anti-Jo-1 and anti-PM-Scl Antibody-positive IIM cases. METHODS: Two hundred and thirty-three adult IIM patients (73% females, 49.4 +/- 13.6 years) with PM (n = 89), DM (n = 88) and myositis associated with another CTD (n = 55) and 85 juvenile DM patients (75% females, 6.2 +/- 3.6 years) were compared with 678 UK Caucasian controls. Patients/controls were genotyped for HLA-DPB1 and DRB1 alleles. Myositis-specific and associated antibodies were identified in cases using immunoprecipitation. RESULTS: HLA-DPB1*0101 was associated with IIM overall [22 vs 13% controls, corrected probability (P(corr)) = 2 x 10(-03); odds ratio (OR) 2.0; 95% CI 1.4, 2.9], PM (P(corr) = 7 x 10(-03); OR 2.5; 95% CI 1.5, 4.4) and anti-Jo-1 (P(corr) = 3 x 10(-5); OR 4.1; 95% CI 2.1, 7.8). No significant DPB1*0101 difference was present between anti-PM-Scl cases and controls. The HLA-DPB1*0101 association in IIM overall cases was dependent on the presence of DRB1*03. A number of HLA-DRB1*03/DPB1 haplotypes were identified, but only DRB1*03/DPB1*0101 was associated with anti-Jo-1 Antibody-positive cases. CONCLUSIONS: The HLA-DRB1*03/DPB1*0101 haplotype is a risk factor for anti-Jo-1 Antibody-positive IIM. Thus, although DRB1*03 is strongly associated with possession of either anti-Jo-1 or anti-PM-Scl, differing Antibody associations are observed at the HLA-DPB1 locus.
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Characterization and peripheral blood biomarker assessment of anti-Jo-1 Antibody-positive interstitial lung disease
Arthritis and Rheumatism, 2009Co-Authors: Thomas J Richards, Aaron Eggebeen, Kevin Gibson, Samuel Yousem, Bernadette R. Gochuico, N. Fertig, Naftali Kaminski, Claire Fuhrman, Carmine V. Oddis, Ivan O. RosasAbstract:OBJECTIVE: Using a combination of clinical, radiographic, functional, and serum protein biomarker assessments, this study was aimed at defining the prevalence and clinical characteristics of interstitial lung disease (ILD) in a large cohort of patients with anti-Jo-1 antibodies. METHODS: A review of clinical records, pulmonary function test results, and findings on imaging studies determined the existence of ILD in anti-Jo-1 Antibody-positive individuals whose data were accumulated in the University of Pittsburgh Myositis Database from 1982 to 2007. Multiplex enzyme-linked immunosorbent assays (ELISAs) for serum inflammation markers, cytokines, chemokines, and matrix metalloproteinases in different patient subgroups were performed to assess the serum proteins associated with anti-Jo-1 Antibody-positive ILD. RESULTS: Among the 90 anti-Jo-1 Antibody-positive individuals with sufficient clinical, radiographic, and/or pulmonary function data, 77 (86%) met the criteria for ILD. While computed tomography scans revealed a variety of patterns suggestive of underlying usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia, a review of the histopathologic abnormalities in a subset of patients undergoing open lung biopsy or transplantation or whose lung tissue was obtained at autopsy (n = 22) demonstrated a preponderance of UIP and diffuse alveolar damage. Analysis by multiplex ELISA yielded statistically significant associations between anti-Jo-1 Antibody-positive ILD and elevated serum levels of C-reactive protein (CRP), CXCL9, and CXCL10, which distinguished this disease entity from idiopathic pulmonary fibrosis and anti-signal recognition particle Antibody-positive myositis. Recursive partitioning further demonstrated that combinations of these and other serum protein biomarkers can distinguish these disease subgroups at high levels of sensitivity and specificity. CONCLUSION: In this large cohort of anti-Jo-1 Antibody-positive individuals, the incidence of ILD approached 90%. Multiplex ELISA demonstrated disease-specific associations between anti-Jo-1 Antibody-positive ILD and serum levels of CRP as well as the interferon-gamma-inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD.
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anti Jo 1 Antibody levels correlate with disease activity in idiopathic inflammatory myopathy
Arthritis & Rheumatism, 2007Co-Authors: Kerry B Stone, N. Fertig, Carmine V. Oddis, Yasuhiro Katsumata, Mary Lucas, Molly T Vogt, Robyn T Domsic, Dana P AschermanAbstract:Objective Previous case series have examined the relationship between anti–Jo-1 Antibody levels and myositis disease activity, demonstrating equivocal results. Using enzyme-linked immunosorbent assays (ELISAs) and novel measures of myositis disease activity, the current study was undertaken to systematically reexamine the association between anti–Jo-1 Antibody levels and various disease manifestations of myositis. Methods Serum anti–Jo-1 Antibody levels were quantified using 2 independent ELISA methods, while disease activity was retrospectively graded using the Myositis Disease Activity Assessment Tool, which measures disease activity in 7 different organ systems via the Myositis Disease Activity Assessment Visual Analog Scale (VAS) and the Myositis Intention-to-Treat Index (MITAX) components. Spearman's rank correlation coefficients and mixed linear regression analysis were used to identify associations between anti–Jo-1 Antibody levels and organ-specific disease activity in cross-sectional and longitudinal analyses, respectively. Results Cross-sectional assessment of 81 patients with anti–Jo-1 Antibody revealed a modest correlation between the anti–Jo-1 Antibody level and the serum creatine kinase (CK) level, as well as muscle and Joint disease activity. Correlation coefficients were similar for CK levels (rs = 0.38, P = 0.002), myositis VAS (rs = 0.36, P = 0.002), and arthritis VAS (rs = 0.40, P = 0.001). In multiple regression analyses of 11 patients with serial samples, anti–Jo-1 Antibody levels correlated significantly with CK levels (R2 = 0.65, P = 0.0002), myositis VAS (R2 = 0.53, P = 0.0008), arthritis VAS (R2 = 0.53, P = 0.006), pulmonary VAS (R2 = 0.69, P = 0.005), global VAS (R2 = 0.63, P = 0.002), and global MITAX (R2 = 0.64, P = 0.0003). Conclusion In this large series of patients with idiopathic inflammatory myopathy, anti–Jo-1 Antibody levels correlated modestly with muscle and Joint disease, an association confirmed by a custom ELISA using recombinant human Jo-1. More striking associations emerged in a smaller longitudinal subset of patients that link anti–Jo-1 Antibody levels to muscle, Joint, lung, and global disease activity.