Abstract
BackgroundSplenectomy is the most effective treatment for patients with primary immune thrombocytopenia (ITP) who fail to respond to steroid therapy. Thus far, there is no effective means to predict the long-term haematological response of the procedure. The purpose of this study was to identify serum biomarkers as predictors of long-term response based on a proteomics approach.MethodsThe serum samples of ITP patients were collected before splenectomy and seven days after surgery. After depletion of the abundant serum proteins, pooled preoperative serum samples from four responders to splenectomy, four nonresponders and four healthy controls were subjected to two-dimensional gel electrophoresis (2-DE). Nine protein spots with at least a five-fold alteration in expression between responders and nonresponders were all identified as haptoglobin (Hp) by matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometer (MS) analysis. The validation of serum Hp expression was performed using enzyme-linked immunosorbent assays (ELISA) in thirty-seven responders, thirteen nonresponders and twenty-one healthy controls.ResultsThe preoperative serum levels of Hp in the nonresponders (925.9 ± 293.5 μg/ml) were significantly lower than those in the responders (1417.4 ± 315.0 μg/ml, p <0.001) and the healthy controls (1409.1 ± 354.2 μg/ml, p <0.001), while there was no significant difference between the latter two groups. The postoperative serum levels of Hp in responders and nonresponders were (1414.1 ± 225.0 μg/ml) and (952.9 ± 202.4 μg/ml), respectively. There were no significant differences between the serum Hp levels before and after surgery in both responders and nonresponders (p>0.05). The preoperative serum levels of Hp did not significantly correlate with preoperative platelet count of the same blood samples (r = 0.244, p = 0.087), while it positively correlated with postoperative peak platelet count (r = 0.622, p < 0.001). The optimal cutoff value of preoperative serum Hp levels (1173.80 μg/ml) derived from the receiver operating characteristic (ROC) curve led to 78.4% sensitivity and 84.6% specificity.ConclusionsThese results suggest that serum Hp levels may serve as a favourable predictor for the long-term response to splenectomy in ITP and may help to understand the pathophysiological differences between responders and nonresponders.
Highlights
Splenectomy is the most effective treatment for patients with primary immune thrombocytopenia (ITP) who fail to respond to steroid therapy
Identification of Hp by Two-dimensional gel electrophoresis (2-DE) separation and MALDI-TOF/ TOF-mass spectrometer (MS) analyses Pooled preoperative serum proteins from four patients in the responder group, four in the nonresponder group, and four healthy controls were subjected to 2-DE separation
Our previous study found that the postoperative peak platelet count was closely correlated with the long-term response of splenectomy in ITP patients [35]
Summary
Splenectomy is the most effective treatment for patients with primary immune thrombocytopenia (ITP) who fail to respond to steroid therapy. There is no effective means to predict the long-term haematological response of the procedure. The purpose of this study was to identify serum biomarkers as predictors of long-term response based on a proteomics approach. The main mechanisms of ITP are anti-platelet autoantibody-mediated platelet destruction and inhibition of thrombopoiesis [2]. Other mechanisms such as abnormal T-helper cells type 1 (Th1) and type 2 (Th2) responses, complement activation, and direct T-cell cytotoxicity were found in ITP patients [2]. Splenectomy for ITP is often associated with the risk of major morbidity and mortality, and the long-term haematological outcomes of the procedure cannot be predicted through routinely available measures [4].
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