Functional Analysis of Autoantibody Signatures in Rheumatoid Arthritis
For the identification of antigenic protein biomarkers for rheumatoid arthritis (RA), we conducted IgG profiling on high density protein microarrays. Plasma IgG of 96 human samples (healthy controls, osteoarthritis, seropositive and seronegative RA, <i>n</i> = 24 each) and time-series pl...
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MDPI AG
2022-02-01
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| Online Access: | https://www.mdpi.com/1420-3049/27/4/1452 |
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| author | Lisa Milchram Anita Fischer Jasmin Huber Regina Soldo Daniela Sieghart Klemens Vierlinger Stephan Blüml Günter Steiner Andreas Weinhäusel |
| author_facet | Lisa Milchram Anita Fischer Jasmin Huber Regina Soldo Daniela Sieghart Klemens Vierlinger Stephan Blüml Günter Steiner Andreas Weinhäusel |
| author_sort | Lisa Milchram |
| collection | DOAJ |
| description | For the identification of antigenic protein biomarkers for rheumatoid arthritis (RA), we conducted IgG profiling on high density protein microarrays. Plasma IgG of 96 human samples (healthy controls, osteoarthritis, seropositive and seronegative RA, <i>n</i> = 24 each) and time-series plasma of a pristane-induced arthritis (PIA) rat model (<i>n</i> = 24 total) were probed on AIT’s 16k protein microarray. To investigate the analogy of underlying disease pathways, differential reactivity analysis was conducted. A total of <i>n</i> = 602 differentially reactive antigens (DIRAGs) at a significance cutoff of <i>p</i> < 0.05 were identified between seropositive and seronegative RA for the human samples. Correlation with the clinical disease activity index revealed an inverse correlation of antibodies against self-proteins found in pathways relevant for antigen presentation and immune regulation. The PIA model showed <i>n</i> = 1291 significant DIRAGs within acute disease. Significant DIRAGs for (I) seropositive, (II) seronegative and (III) PIA were subjected to the Reactome pathway browser which also revealed pathways relevant for antigen presentation and immune regulation; of these, seven overlapping pathways had high significance. We therefore conclude that the PIA model reflects the biological similarities of the disease pathogenesis. Our data show that protein array analysis can elucidate biological differences and pathways relevant in disease as well be a useful additional layer of omics information. |
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| language | English |
| last_indexed | 2024-03-09T21:19:59Z |
| publishDate | 2022-02-01 |
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| series | Molecules |
| spelling | doaj.art-96a1c2f22b5f4d2c967e088a56e90bb82023-11-23T21:24:11ZengMDPI AGMolecules1420-30492022-02-01274145210.3390/molecules27041452Functional Analysis of Autoantibody Signatures in Rheumatoid ArthritisLisa Milchram0Anita Fischer1Jasmin Huber2Regina Soldo3Daniela Sieghart4Klemens Vierlinger5Stephan Blüml6Günter Steiner7Andreas Weinhäusel8Center for Health and Bioresources, Molecular Diagnostics, AIT Austrian Institute of Technology GmbH, Giefinggasse 4, 1210 Vienna, AustriaDepartment of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, AustriaCenter for Health and Bioresources, Molecular Diagnostics, AIT Austrian Institute of Technology GmbH, Giefinggasse 4, 1210 Vienna, AustriaCenter for Health and Bioresources, Molecular Diagnostics, AIT Austrian Institute of Technology GmbH, Giefinggasse 4, 1210 Vienna, AustriaDepartment of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, AustriaCenter for Health and Bioresources, Molecular Diagnostics, AIT Austrian Institute of Technology GmbH, Giefinggasse 4, 1210 Vienna, AustriaDepartment of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, AustriaDepartment of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, AustriaCenter for Health and Bioresources, Molecular Diagnostics, AIT Austrian Institute of Technology GmbH, Giefinggasse 4, 1210 Vienna, AustriaFor the identification of antigenic protein biomarkers for rheumatoid arthritis (RA), we conducted IgG profiling on high density protein microarrays. Plasma IgG of 96 human samples (healthy controls, osteoarthritis, seropositive and seronegative RA, <i>n</i> = 24 each) and time-series plasma of a pristane-induced arthritis (PIA) rat model (<i>n</i> = 24 total) were probed on AIT’s 16k protein microarray. To investigate the analogy of underlying disease pathways, differential reactivity analysis was conducted. A total of <i>n</i> = 602 differentially reactive antigens (DIRAGs) at a significance cutoff of <i>p</i> < 0.05 were identified between seropositive and seronegative RA for the human samples. Correlation with the clinical disease activity index revealed an inverse correlation of antibodies against self-proteins found in pathways relevant for antigen presentation and immune regulation. The PIA model showed <i>n</i> = 1291 significant DIRAGs within acute disease. Significant DIRAGs for (I) seropositive, (II) seronegative and (III) PIA were subjected to the Reactome pathway browser which also revealed pathways relevant for antigen presentation and immune regulation; of these, seven overlapping pathways had high significance. We therefore conclude that the PIA model reflects the biological similarities of the disease pathogenesis. Our data show that protein array analysis can elucidate biological differences and pathways relevant in disease as well be a useful additional layer of omics information.https://www.mdpi.com/1420-3049/27/4/1452rheumatoid arthritisautoantibodiesseroreactivitydisease activityrat modelpathway analysis |
| spellingShingle | Lisa Milchram Anita Fischer Jasmin Huber Regina Soldo Daniela Sieghart Klemens Vierlinger Stephan Blüml Günter Steiner Andreas Weinhäusel Functional Analysis of Autoantibody Signatures in Rheumatoid Arthritis Molecules rheumatoid arthritis autoantibodies seroreactivity disease activity rat model pathway analysis |
| title | Functional Analysis of Autoantibody Signatures in Rheumatoid Arthritis |
| title_full | Functional Analysis of Autoantibody Signatures in Rheumatoid Arthritis |
| title_fullStr | Functional Analysis of Autoantibody Signatures in Rheumatoid Arthritis |
| title_full_unstemmed | Functional Analysis of Autoantibody Signatures in Rheumatoid Arthritis |
| title_short | Functional Analysis of Autoantibody Signatures in Rheumatoid Arthritis |
| title_sort | functional analysis of autoantibody signatures in rheumatoid arthritis |
| topic | rheumatoid arthritis autoantibodies seroreactivity disease activity rat model pathway analysis |
| url | https://www.mdpi.com/1420-3049/27/4/1452 |
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