Altered IGF-1R, p70S6K, and GSK-3β expression in PBMCs of immune thrombocytopenia patients and clinical associations

Abstract

Objective

To investigate the expression profiles of insulin-like growth factor-1 receptor (IGF-1R), p70S6 kinase (p70S6K), and glycogen synthase kinase-3β (GSK-3β) in peripheral blood mononuclear cells (PBMCs) of adults with newly diagnosed primary immune thrombocytopenia (ITP), and to evaluate their associations with clinical hematologic parameters.

Methods

A case-control study was conducted enrolling 30 adults with newly diagnosed primary ITP and 28 healthy volunteers. PBMCs were isolated from peripheral venous blood. The expression levels of Akt/mTOR pathway-related proteins were quantified using a high-throughput multiplex Luminex xMAP platform. Statistical analyses were performed to compare protein levels between the ITP and control groups and to assess the correlations between these signaling molecules and peripheral blood indices, specifically platelet counts. In addition, a small cohort of patients with chemotherapy-induced thrombocytopenia (CTIT) was included in the RT-qPCR validation analysis to further explore disease specificity.

Results

Compared with healthy controls, patients with ITP showed significantly elevated protein levels of IGF-1R and GSK-3β in PBMCs after FDR correction, whereas p70S6K showed only a nominal increase that did not remain significant after multiple-testing correction. RT-qPCR validation further showed significant upregulation of p70S6K and GSK-3β mRNA levels, with a concordant but non-significant increasing trend in IGF-1R mRNA. No significant differences were observed in other pathway components (e.g., Akt, mTOR, PTEN) or across different age and gender subgroups within the patient cohort. Notably, the expression levels of IGF-1R and p70S6K showed a significant negative correlation with peripheral platelet counts (P < 0.05), whereas no significant associations were found with red blood cell counts, hemoglobin, or white blood cell counts. In the validation analysis, comparison with the chemotherapy-induced thrombocytopenia cohort suggested that these alterations were more pronounced in ITP rather than representing a nonspecific consequence of thrombocytopenia.

Conclusion

The altered expression of IGF-1R and GSK-3β, together with the potential involvement of p70S6K supported by transcriptional validation, may be associated with thrombocytopenia severity in newly diagnosed ITP, suggesting dysregulation of immunometabolic signaling in PBMCs.