The Platelet-Specific Gene Signature in the Immunoglobulin G4-Related Disease Transcriptome
<i>Background and Objectives:</i> Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated, fibroinflammatory, multiorgan disease with an obscure pathogenesis. Findings indicating excessive platelet activation have been reported in systemic sclerosis, which is another autoimmune...
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2025-01-01
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| author | Ali Kemal Oguz Cagdas Sahap Oygur Bala Gur Dedeoglu Irem Dogan Turacli Sibel Serin Kilicoglu Ihsan Ergun |
| author_facet | Ali Kemal Oguz Cagdas Sahap Oygur Bala Gur Dedeoglu Irem Dogan Turacli Sibel Serin Kilicoglu Ihsan Ergun |
| author_sort | Ali Kemal Oguz |
| collection | DOAJ |
| description | <i>Background and Objectives:</i> Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated, fibroinflammatory, multiorgan disease with an obscure pathogenesis. Findings indicating excessive platelet activation have been reported in systemic sclerosis, which is another autoimmune, multisystemic fibrotic disorder. The immune-mediated, inflammatory, and fibrosing intersections of IgG4-RD and systemic sclerosis raised a question about platelets’ role in IgG4-RD. <i>Materials and Methods</i>: By borrowing transcriptomic data from Nakajima et al. (GEO repository, GSE66465) we sought a platelet contribution to the pathogenesis of IgG4-RD. GEO2R and BRB-ArrayTools were used for class comparisons, and WebGestalt for functional enrichment analysis. During the selection of differentially expressed genes (DEGs), the translationally active but significantly low amount of platelet mRNA was specifically considered. The platelet-specific gene signature derived was used for cluster analysis of patient and control groups. <i>Results</i>: When IgG4-RD patients were compared with controls, 268 DEGs (204 with increased and 64 with decreased expression) were detected. Among these, a molecular signature of 22 platelet-specific genes harbored genes important for leukocyte–platelet aggregate formation (i.e., <i>CLEC1B</i>, <i>GP1BA</i>, <i>ITGA2B</i>, <i>ITGB3</i>, <i>SELP</i>, and <i>TREML1</i>) and extracellular matrix synthesis (i.e., <i>CLU</i>, <i>PF4</i>, <i>PPBP</i>, <i>SPARC</i>, and <i>THBS1</i>). Functional enrichment analysis documented significantly enriched terms related to platelets, including but not limited to “platelet reactivity”, “platelet degranulation”, “platelet aggregation”, and “platelet activation”. During clustering, the 22 gene signatures successfully discriminated IgG4-RD and the control and the IgG4-RD before and after treatment groups. <i>Conclusions</i>: Patients with IgG4-RD apparently display an activated platelet phenotype with a potential contribution to disease immunopathogenesis. If the platelets’ role is validated through further carefully designed research, the therapeutic potentials of selected conventional and/or novel antiplatelet agents remain to be evaluated in patients with IgG4-RD. Transcriptomics and/or proteomics research with platelets should take into account the relatively low amounts of platelet mRNA, miRNA, and protein. Secondary analysis of omics data sets has great potential to reveal new and valuable information. |
| format | Article |
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| institution | Kabale University |
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| publishDate | 2025-01-01 |
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| spelling | doaj-art-eb885a8497d34c6e828acc703af3092c2025-01-24T13:40:56ZengMDPI AGMedicina1010-660X1648-91442025-01-0161116210.3390/medicina61010162The Platelet-Specific Gene Signature in the Immunoglobulin G4-Related Disease TranscriptomeAli Kemal Oguz0Cagdas Sahap Oygur1Bala Gur Dedeoglu2Irem Dogan Turacli3Sibel Serin Kilicoglu4Ihsan Ergun5Department of Internal Medicine, Faculty of Medicine, Ufuk University, 06510 Ankara, TurkeyDepartment of Internal Medicine (Rheumatology), Faculty of Medicine, Baskent University, 06490 Ankara, TurkeyDepartment of Biotechnology, Biotechnology Institute, Ankara University, 06135 Ankara, TurkeyDepartment of Medical Biology, Faculty of Medicine, Ufuk University, 06510 Ankara, TurkeyDepartment of Histology & Embryology, Faculty of Medicine, Baskent University, 06790 Ankara, TurkeyDepartment of Internal Medicine (Nephrology), Faculty of Medicine, Ufuk University, 06510 Ankara, Turkey<i>Background and Objectives:</i> Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated, fibroinflammatory, multiorgan disease with an obscure pathogenesis. Findings indicating excessive platelet activation have been reported in systemic sclerosis, which is another autoimmune, multisystemic fibrotic disorder. The immune-mediated, inflammatory, and fibrosing intersections of IgG4-RD and systemic sclerosis raised a question about platelets’ role in IgG4-RD. <i>Materials and Methods</i>: By borrowing transcriptomic data from Nakajima et al. (GEO repository, GSE66465) we sought a platelet contribution to the pathogenesis of IgG4-RD. GEO2R and BRB-ArrayTools were used for class comparisons, and WebGestalt for functional enrichment analysis. During the selection of differentially expressed genes (DEGs), the translationally active but significantly low amount of platelet mRNA was specifically considered. The platelet-specific gene signature derived was used for cluster analysis of patient and control groups. <i>Results</i>: When IgG4-RD patients were compared with controls, 268 DEGs (204 with increased and 64 with decreased expression) were detected. Among these, a molecular signature of 22 platelet-specific genes harbored genes important for leukocyte–platelet aggregate formation (i.e., <i>CLEC1B</i>, <i>GP1BA</i>, <i>ITGA2B</i>, <i>ITGB3</i>, <i>SELP</i>, and <i>TREML1</i>) and extracellular matrix synthesis (i.e., <i>CLU</i>, <i>PF4</i>, <i>PPBP</i>, <i>SPARC</i>, and <i>THBS1</i>). Functional enrichment analysis documented significantly enriched terms related to platelets, including but not limited to “platelet reactivity”, “platelet degranulation”, “platelet aggregation”, and “platelet activation”. During clustering, the 22 gene signatures successfully discriminated IgG4-RD and the control and the IgG4-RD before and after treatment groups. <i>Conclusions</i>: Patients with IgG4-RD apparently display an activated platelet phenotype with a potential contribution to disease immunopathogenesis. If the platelets’ role is validated through further carefully designed research, the therapeutic potentials of selected conventional and/or novel antiplatelet agents remain to be evaluated in patients with IgG4-RD. Transcriptomics and/or proteomics research with platelets should take into account the relatively low amounts of platelet mRNA, miRNA, and protein. Secondary analysis of omics data sets has great potential to reveal new and valuable information.https://www.mdpi.com/1648-9144/61/1/162blood plateletsimmunoglobulin G4-related diseasegene expression profilingtranscriptomeplatelet activationfibrosis |
| spellingShingle | Ali Kemal Oguz Cagdas Sahap Oygur Bala Gur Dedeoglu Irem Dogan Turacli Sibel Serin Kilicoglu Ihsan Ergun The Platelet-Specific Gene Signature in the Immunoglobulin G4-Related Disease Transcriptome Medicina blood platelets immunoglobulin G4-related disease gene expression profiling transcriptome platelet activation fibrosis |
| title | The Platelet-Specific Gene Signature in the Immunoglobulin G4-Related Disease Transcriptome |
| title_full | The Platelet-Specific Gene Signature in the Immunoglobulin G4-Related Disease Transcriptome |
| title_fullStr | The Platelet-Specific Gene Signature in the Immunoglobulin G4-Related Disease Transcriptome |
| title_full_unstemmed | The Platelet-Specific Gene Signature in the Immunoglobulin G4-Related Disease Transcriptome |
| title_short | The Platelet-Specific Gene Signature in the Immunoglobulin G4-Related Disease Transcriptome |
| title_sort | platelet specific gene signature in the immunoglobulin g4 related disease transcriptome |
| topic | blood platelets immunoglobulin G4-related disease gene expression profiling transcriptome platelet activation fibrosis |
| url | https://www.mdpi.com/1648-9144/61/1/162 |
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