Granulocyte antigens play an important role in cell function including adhesion, cell activation, and binding of immunoglobulins. The purpose of these studies is to better define the molecular basis of variations in neutrophil antigens and their role in neutrophil function. Neutrophil-specific antigen HNA-2a (NB1) has been localized to NB1 glycoprotein (gp) which is expressed on subpopulations of neutrophils. The gene encoding the NB1 gp was recently sequenced and called NB1. Another group described a gene called PRV-1 that is highly homologous to NB1. We found that NB1 and PRV-1 are alleles of the same gene, CD177, and showed that this gene is located on chromosome 19q13.31. In addition, we found that a pseudo gene homologous to exons 4 through 9 of CD177 was located on adjacent to CD177 on chromosome 19q13.31. The most common polymorphisms of CD177 was found to be a G to C change at bp42. Recently, CD177 has been found to be over expressed in neutrophils from patients with polycythemia vera. On going studies are using the leukemia cell line HL60 to characterize the molecular mechanisms responsible for CD177 expression. We are also investing the investigate the molecular basis for the variable expression of CD177 and the expression of CD177 in patients with myeloproliferative diseases.? ? Durning pregnancy or following transfusion people often make antibodies directed to antigens expressed by neutrophils. When blood donors produce these antibodies to neutrophil specific antigens the inadvertant transfusion of these antibodies has been associated with transfusion reactions. However, not all patients given blood products with neutrophil antibodies experience a transfusion and the type of transfusion reactions varies among individuals. Studies are underway to investigate the role of antibodies directed to luekocytes in transfusion reactions.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL002095-11
Application #
7593043
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2007
Total Cost
$41,216
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Slezak, Stefanie; Jin, Ping; Caruccio, Lorraine et al. (2009) Gene and microRNA analysis of neutrophils from patients with polycythemia vera and essential thrombocytosis: down-regulation of micro RNA-1 and -133a. J Transl Med 7:39
Shin, Jeong Won; Jin, Ping; Fan, Yong et al. (2008) Evaluation of gene expression profiles of immature dendritic cells prepared from peripheral blood mononuclear cells. Transfusion 48:647-57
Slezak, S L; Adams, S; Lee-Stroka, H et al. (2008) Rapid, single-subject genotyping to predict red blood cell antigen expression. Immunohematology 24:154-9
Shin, Jeung Won; Jin, Ping; Stroncek, David (2008) [Effect of leukapheresis on gene expression profiles of donor's peripheral blood mononuclear cells] Korean J Lab Med 28:130-5
Lee-Stroka, Hallie; Slezak, Stefanie L; Adams, Sharon et al. (2008) Another example of a KEL1 variant red cell phenotype due to a threonine to serine change at position 193 of Kell glycoprotein. Transfusion 48:925-9
Stroncek, David F; Fadeyi, Emmanuel; Adams, Sharon (2007) Leukocyte antigen and antibody detection assays: tools for assessing and preventing pulmonary transfusion reactions. Transfus Med Rev 21:273-86
Fadeyi, Emmanuel A; De Los Angeles Muniz, Maria; Wayne, Alan S et al. (2007) The transfusion of neutrophil-specific antibodies causes leukopenia and a broad spectrum of pulmonary reactions. Transfusion 47:545-50
Stroncek, David F (2007) Pulmonary transfusion reactions. Semin Hematol 44:2-14
Stroncek, David F; Klein, Harvey G (2007) Heavy breathing in the blood bank: is it transfusion-related acute lung injury, our anxiety, or both? Transfusion 47:559-62
Bennett, Michael; Stroncek, David F (2006) Recent advances in the bcr-abl negative chronic myeloproliferative diseases. J Transl Med 4:41

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