Research

Serum proteomic profiling and haptoglobin polymorphisms in patients with GVHD after allogeneic hematopoietic cell transplantation

Joseph McGuirk^1,5 , Gang Hao³ , Weijian Hou¹ , Sunil Abhyankar¹ , Casey Williams¹ , Weisi Yan³ , Jianda Yuan⁴ , Xiuqin Guan² , Robert Belt¹ , Shaun Dejarnette¹ , Jeffery Wieman¹ and Ying Yan^1,2

¹  Blood and Marrow Transplantation Program, Saint Luke's Cancer Institute, Kansas City, Missouri, USA

²  Department of Medicine, School of Medicine, University Missouri-Kansas City, Kansas City, Missouri, USA

³  Department of Pharmacology, Weill Medical College of Cornell University, New York, New York, USA

⁴  Laboratory of Cellular Immunobiology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

⁵  Blood and Marrow Transplant Program, The University of Kansas Hospital Cancer Center, 2330 Shawnee Mission Parkway, Westwood, Kansas 66205, USA

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Journal of Hematology & Oncology 2009, 2:17doi:10.1186/1756-8722-2-17

Published:	20 April 2009

Abstract

We studied serum proteomic profiling in patients with graft versus host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) by two-dimensional gel electrophoresis (2-DE) and mass spectrometry analysis. The expression of a group of proteins, haptoglobin (Hp), alpha-1-antitrypsin, apolipoprotein A-IV, serum paraoxonase and Zn-alpha-glycoprotein were increased and the proteins, clusterin precursor, alpha-2-macroglobulin, serum amyloid protein precursor, sex hormone-binding globulin, serotransferrin and complement C4 were decreased in patients with extensive chronic GVHD (cGVHD). Serum haptoglobin (Hp) levels in patients with cGVHD were demonstrated to be statistically higher than in patients without cGVHD and normal controls (p < 0.01). We used immunoblotting and PCR in combination with 2-DE gel image analysis to determine Hp polymorphisms in 25 allo-HCT patients and 16 normal donors. The results demonstrate that patients with cGVHD had a higher incidence of HP 2-2 phenotype (43.8%), in comparison to the patients without cGVHD (0%) and normal donors (18.7%), suggesting the possibility that specific Hp polymorphism may play a role in the development of cGVHD after allo-HCT. In this study, quantitative serum Hp levels were shown to be related to cGVHD development. Further, the data suggest the possibility that specific Hp polymorphisms may be associated with cGVHD development and warrant further investigation.