Novel biomarkers for the differential diagnosis of paediatric MYH9-related diseases and immune thrombocytopenia revealed by plasma proteomics

Abstract

Differentiating myosin heavy chain 9 (MYH9)-related disease (MYH9-RD) from immune thrombocytopenia (ITP) remains clinically challenging. This study utilized data-independent acquisition (DIA) plasma proteomics to identify distinguishing biomarker signatures. Profiling cohorts of MYH9-RD (n = 10), ITP (n = 10) and healthy controls (n = 14) quantified 2533 proteins, revealing distinct immune and metabolic remodelling. We identified 91 MYH9-RD-specific and 124 ITP-specific proteins, highlighting divergent organ involvement pathways. By integrating protein–protein interaction networks with Boruta and Random Forest machine-learning algorithms, we identified preliminary candidate biomarker panels (MYH9-RD panel: von Willebrand factor [VWF], cholesteryl ester transfer protein [CETP], apolipoprotein A-1 [APOA1], periostin [POSTN]; ITP panel: neutrophil gelatinase-associated lipocalin [NGAL], plasminogen activator inhibitor-1 [PAI-1], carboxypeptidase B2 [CPB2]) that demonstrated excellent apparent discrimination. This exploratory study provides a hypothesis-generating framework, revealing fundamentally distinct molecular landscapes between congenital and acquired macrothrombocytopenia. Pending rigorous future external validation, these preliminary candidate biomarkers offer novel biological insights into the divergent pathophysiologies of MYH9-RD and ITP.