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pmid:39859144

The Platelet-Specific Gene Signature in the Immunoglobulin G4-Related Disease Transcriptome.

Ali Kemal Oguz · Cagdas Sahap Oygur · Bala Gur Dedeoglu · Irem Dogan Turacli · Sibel Serin Kilicoglu · Ihsan Ergun

Medicina (Kaunas, Lithuania) · 2025 doi:10.3390/medicina61010162

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

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The Platelet-Specific Gene Signature in the Immunoglobulin G4-Related Disease Transcriptome.
doi
10.3390/medicina61010162
pmid
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[0]
Ali Kemal Oguz
[1]
Cagdas Sahap Oygur
[2]
Bala Gur Dedeoglu
[3]
Irem Dogan Turacli
[4]
Sibel Serin Kilicoglu
[5]
Ihsan Ergun
journal
Medicina (Kaunas, Lithuania)
year
2025
abstract
Background and Objectives: 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. Materials and Methods: 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. Results: 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., CLEC1B, GP1BA, ITGA2B, ITGB3, SELP, and TREML1) and extracellular matrix synthesis (i.e., CLU, PF4, PPBP, SPARC, and THBS1). 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. Conclusions: 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.
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Class comparison analyses between the IgG4-RD patients and control groups were performed using GEO2R [23]. The default settings of GEO2R were preserved (i.e., “Benjamini–Hochberg procedure” to control the false discovery rate, “auto-detect” option to apply log transformation to the data, “no” for the vooma function, “no” for forcing normalization, “NCBI generated” annotations and “0.05” for the cut-off level of significance).
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All the bioinformatics data supporting the findings of this study are either presented within the manuscript or within the Supplementary Materials Files accompanying the manuscript. The microarray expression data of the study by Nakajima et al. can be obtained through the Gene Expression Omnibus data repository with the accession number GSE66465 [19].
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All the bioinformatics data supporting the findings of this study are either presented within the manuscript or within the Supplementary Materials Files accompanying the manuscript. The microarray expression data of the study by Nakajima et al. can be obtained through the Gene Expression Omnibus data repository with the accession number GSE66465 [19].
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When IgG4-RD patients were compared with controls, 268 DEGs (204 with increased and 64 with decreased expression) were detected.
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All the bioinformatics data supporting the findings of this study are either presented within the manuscript or within the Supplementary Materials Files accompanying the manuscript. The microarray expression data of the study by Nakajima et al. can be obtained through the Gene Expression Omnibus data repository with the accession number GSE66465 [19].
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Gene expression patterns in IgG4-RD before and after steroid treatment and healthy control groups
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Class comparison analyses between the IgG4-RD patients and control groups were performed using GEO2R [23]. The default settings of GEO2R were preserved (i.e., “Benjamini–Hochberg procedure” to control the false discovery rate, “auto-detect” option to apply log transformation to the data, “no” for the vooma function, “no” for forcing normalization, “NCBI generated” annotations and “0.05” for the cut-off level of significance).
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