Shared Inflammatory Gene Programs between Immune Thrombocytopenia and CKD-Related Autoimmune Nephropathies: An Exploratory Transcriptomic and Bioinformatic Study

Xin He; Meiling Jin; Qianmei Sun

doi:10.2478/bjmg-2025-00027

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Shared Inflammatory Gene Programs between Immune Thrombocytopenia and CKD-Related Autoimmune Nephropathies: An Exploratory Transcriptomic and Bioinformatic Study

Balkan Journal of Medical Genetics

Volume 28 (2025): Issue 2 (December 2025)

By: Xin He, Meiling Jin and Qianmei Sun

Open Access

|May 2026

Abstract

Objective

To define peripheral transcriptomic alterations in newly diagnosed immune thrombocytopenia (ITP) and explore shared disease-associated gene programs with chronic kidney disease (CKD) related autoimmune nephropathies (membranous nephropathy, MN; IgA nephropathy, IgAN).

Methods

CD19+ B cells from newly diagnosed ITP patients and healthy controls (n = 4/group) underwent high-throughput sequencing. To complement the limited cohort, six publicly available ITP-related GEO datasets were additionally collected as supplementary transcriptomic resources. Differential expression analyses were performed separately in the dataset and the public datasets using dataset-appropriate workflows, and the intersecting differentially expressed genes were retained as common DEGs for downstream analyses. Functional enrichment was assessed using GSEA, and candidate genes were prioritized using machine-learning approaches, including LASSO, SVM-RFE, and Random Forest, followed by protein-protein interaction (PPI) network analysis. TNF, NLRP3, and IL1B were further validated by qPCR in newly diagnosed ITP patients, remission ITP patients, and healthy controls. CKD, MN and IgAN associated gene sets were curated from GeneCards and OMIM for overlap and PPI analyses.

Results

Intersecting the differential expression results from the and public datasets yielded 498 common DEGs, including 243 upregulated and 255 downregulated genes. These genes were enriched in inflammatory and immunometabolic pathways. Machine learning analyses converged on SRGN as a prioritized candidate gene. PPI analysis highlighted inflammatory and immune-related nodes, including TNF and IL1B, while qPCR confirmed increased expression of TNF, NLRP3, and IL1B in newly diagnosed ITP patients, with reduced NLRP3 and IL1B expression in remission. Overlap analyses identified 39 genes shared with CKD, 24 with MN, and 37 with IgAN, with TNF emerging as a recurrent high-connectivity inflammatory node across the overlap derived PPI networks.

Conclusions

Newly diagnosed ITP is associated with a distinct inflammatory and immunometabolic B-cell transcriptional program. The recurrent identification of TNF centered and inflammasome-linked signals suggests shared disease associated inflammatory components between ITP and CKD related autoimmune nephropathies. These molecular signatures may contribute to future biomarker development, renal risk stratification, or translational targeting across hematologic and renal autoimmunity.

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Articles in this issue

DOI: https://doi.org/10.2478/bjmg-2025-00027 | Journal eISSN: 2199-5761

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Language: English

Page range: 73 - 84

Published on: May 14, 2026

Published by: Macedonian Academy of Sciences and Arts

In partnership with: Paradigm Publishing Services

Publication frequency: 2 issues per year

Keywords:

immune thrombocytopenia,

differentially expressed genes,

chronic kidney disease,

membranous nephropathy,

IgA nephropathy,

protein-protein interaction

Related subjects:

Medicine,

Basic medical science,

Basic medical science, other

© 2026 Xin He, Meiling Jin, Qianmei Sun, published by Macedonian Academy of Sciences and Arts
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Volume 28 (2025): Issue 2 (December 2025)