Premium
Identification of novel biomarkers in chronic immune thrombocytopenia ( ITP ) by microarray‐based serum protein profiling
Author(s) -
Bal Gürkan,
Futschik Matthias E.,
Hartl Daniela,
Ringel Frauke,
KamhiehMilz Julian,
Sterzer Viktor,
Hoheisel Jörg D.,
Alhamdani Mohamed S. S.,
Salama Abdulgabar
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13861
Subject(s) - autoantibody , immunology , antibody , medicine , immune system , peripheral blood mononuclear cell , antibody microarray , thrombopoiesis , microarray , biology , progenitor cell , stem cell , megakaryocyte , gene expression , gene , biochemistry , genetics , in vitro
Summary 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 BCL 2, breast cancer type 1 susceptibility protein ( BRCA 1), 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/ SSA 60, anti‐Ro/ SSA 52, 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 RUNX 1 mRNA expression in the peripheral blood mononuclear cells ( PBMC ) of patients was significantly downregulated, an accumulation of RUNX 1 protein was observed in the platelets of ITP patients. This may indicate dysregulation of RUNX 1 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.