Identification of novel biomarkers in chronic immune thrombocytopenia (<scp>ITP</scp>) by microarray‐based serum protein profiling

<jats:title>Summary</jats:title><jats:p>The pathological mechanisms underlying the development of immune thrombocytopenia (<jats:styled-content style="fixed-case">ITP</jats:styled-content>) are unclear and its diagnosis remains a process of exclusion. Currently, there are no known specific biomarkers for <jats:styled-content style="fixed-case">ITP</jats:styled-content> to support differential diagnosis and treatment decisions. Profiling of serum proteins may be valuable for identifying such biomarkers. Sera from 46 patients with primary chronic <jats:styled-content style="fixed-case">ITP</jats:styled-content> and 34 healthy blood donors were analysed using a microarray of 755 antibodies. We identified 161 differentially expressed proteins. In addition to oncoproteins and tumour‐suppressor proteins, including apoptosis regulator <jats:styled-content style="fixed-case">BCL</jats:styled-content>2, breast cancer type 1 susceptibility protein (<jats:styled-content style="fixed-case">BRCA</jats:styled-content>1), Fanconi anaemia complementation group C (<jats:styled-content style="fixed-case">FANCC</jats:styled-content>) and vascular endothelial growth factor A (<jats:styled-content style="fixed-case">VEGFA</jats:styled-content>), we detected six anti‐nuclear autoantibodies in a subset of <jats:styled-content style="fixed-case">ITP</jats:styled-content> patients: anti‐<jats:styled-content style="fixed-case">PCNA</jats:styled-content>, anti‐SmD, anti‐Ro/<jats:styled-content style="fixed-case">SSA</jats:styled-content>60, anti‐Ro/<jats:styled-content style="fixed-case">SSA</jats:styled-content>52, anti‐La/<jats:styled-content style="fixed-case">SSB</jats:styled-content> and anti‐<jats:styled-content style="fixed-case">RNPC</jats:styled-content> antibodies. This finding may provide a rational explanation for the association of <jats:styled-content style="fixed-case">ITP</jats:styled-content> with malignancies and other autoimmune diseases. While <jats:italic><jats:styled-content style="fixed-case">RUNX</jats:styled-content>1</jats:italic><jats:styled-content style="fixed-case">mRNA</jats:styled-content> expression in the peripheral blood mononuclear cells (<jats:styled-content style="fixed-case">PBMC</jats:styled-content>) of patients was significantly downregulated, an accumulation of <jats:styled-content style="fixed-case">RUNX</jats:styled-content>1 protein was observed in the platelets of <jats:styled-content style="fixed-case">ITP</jats:styled-content> patients. This may indicate dysregulation of <jats:styled-content style="fixed-case">RUNX</jats:styled-content>1 expression in <jats:styled-content style="fixed-case">PBMC</jats:styled-content> and megakaryocytes and may lead to an imbalanced immune response and impaired thrombopoiesis. In conclusion, we provide novel insights into the pathogenic mechanisms of <jats:styled-content style="fixed-case">ITP</jats:styled-content> that warrant further exploration.</jats:p>