title: Identification of novel biomarkers in chronic immune thrombocytopenia (ITP) by microarray-based serum protein profiling.
abstract: The pathological mechanisms underlying the development of immune thrombocytopenia (ITP) are unclear and its diagnosis remains a process of exclusion. Currently, there are no known specific biomarkers for ITP 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 ITP 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 BCL2, breast cancer type 1 susceptibility protein (BRCA1), Fanconi anaemia complementation group C (FANCC) and vascular endothelial growth factor A (VEGFA), we detected six anti-nuclear autoantibodies in a subset of ITP patients: anti-PCNA, anti-SmD, anti-Ro/SSA60, anti-Ro/SSA52, anti-La/SSB and anti-RNPC antibodies. This finding may provide a rational explanation for the association of ITP with malignancies and other autoimmune diseases. While RUNX1mRNA expression in the peripheral blood mononuclear cells (PBMC) of patients was significantly downregulated, an accumulation of RUNX1 protein was observed in the platelets of ITP patients. This may indicate dysregulation of RUNX1 expression in PBMC and megakaryocytes and may lead to an imbalanced immune response and impaired thrombopoiesis. In conclusion, we provide novel insights into the pathogenic mechanisms of ITP that warrant further exploration.
authors.affiliation: Institute for Transfusion Medicine, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Gürkan
authors.identifier: http://orcid.org/0000-0003-0868-4059
authors.initials: G
authors.lastname: Bal
authors.affiliation: Center for Biomedical Research, Universidade do Algarve, Faro, Portugal.
authors.forename: Matthias E
authors.initials: ME
authors.lastname: Futschik
authors.affiliation: Berlin-Brandenburg Centre for Regenerative Therapies (BCRT), Berlin, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Hartl
authors.affiliation: Institute for Transfusion Medicine, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Ringel
authors.affiliation: Institute for Transfusion Medicine, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Kamhieh-Milz
authors.affiliation: Institute for Transfusion Medicine, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Viktor
authors.initials: V
authors.lastname: Sterzer
authors.affiliation: Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Jörg D
authors.initials: JD
authors.lastname: Hoheisel
authors.affiliation: Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Mohamed S S
authors.initials: MS
authors.lastname: Alhamdani
authors.affiliation: Institute for Transfusion Medicine, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Abdulgabar
authors.initials: A
authors.lastname: Salama
mesh_terms: D001323:Autoantibodies / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D001792:Blood Platelets / Q000737:chemistry; D016022:Case-Control Studies; D002908:Chronic Disease; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000276:immunology; D040081:Protein Array Analysis / Q000379:methods; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000175:diagnosis*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; C493728:RUNX1 protein, human; C493729:Runx3 protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: B cell CLL/lymphoma 2; cancer; chronic autoimmune thrombocytopenic purpura; runt-related transcription factor 3; thrombocytopenia