Serum proteomic profiling and haptoglobin polymorphisms in patients with GVHD after allogeneic hematopoietic cell transplantation.
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.
McGuirk
Joseph
J
Blood and Marrow Transplantation Program, Saint Luke's Cancer Institute, Kansas City, Missouri, USA. jmcguirk@kumc.edu
Hao
Gang
G
Hou
Weijian
W
Abhyankar
Sunil
S
Williams
Casey
C
Yan
Weisi
W
Yuan
Jianda
J
Guan
Xiuqin
X
Belt
Robert
R
Dejarnette
Shaun
S
Wieman
Jeffery
J
Yan
Ying
Y
D000328:Adult; D000595:Amino Acid Sequence; D001798:Blood Proteins / Q000032:analysis* / Q000378:metabolism; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000097:blood* / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D006242:Haptoglobins / Q000235:genetics* / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic / Q000502:physiology; D040901:Proteomics; D053719:Tandem Mass Spectrometry; D014184:Transplantation, Homologous; D055815:Young Adult
D001798:Blood Proteins; C485359:HP protein, human; D006242:Haptoglobins