Z Du

Publications (2)8.44 Total impact

• Article: KIR2DL5 alleles mark certain combination of activating KIR genes.

  Z Du, S K Sharma, S Spellman, E F Reed, R Rajalingam
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  ABSTRACT: Killer cell Ig-like receptors (KIR) control the immune response of NK cells and some T cells to infections and tumors. KIR genes evolve rapidly and are variable between individuals in their number, type and sequence. Here, we determined the nature of KIR2DL5 gene polymorphism in four ethnic groups using direct DNA sequencing method. Nine new sequences were discovered. Within the panel of 248 KIR2DL5-positive individuals, 14 KIR2DL5-sequences differing in coding regions were observed. They differed at only seven amino acid positions, and such limited polymorphism is consistent with its conserved nature throughout the hominoid lineage. Ethnic deviation was seen in the distribution of KIR2DL5A, KIR2DL5B and their alleles. African Americans had more KIR2DL5 alleles than other populations indicating that more polymorphisms are yet to be discovered in Africans. Linkage between KIR2DL5-alleles and certain activating-KIR genes were observed, but frequency of these linked clusters differed substantially between populations. Consequently, KIR2DL5 alleles can be used as markers to predict the activating-KIR gene content. Typing system distinguishing A*001 and B*002 alleles can serve as a powerful screening test to assess the content of most variable activating-KIR genes that have been implicated in human disease and in the outcome of hematopoietic stem cell transplantation.
  Genes and immunity 06/2008; 9(5):470-80. · 4.22 Impact Factor
• Article: Combination of KIR and HLA gene variants augments the risk of developing birdshot chorioretinopathy in HLA-A*29-positive individuals.

  R D Levinson, Z Du, L Luo, D Monnet, T Tabary, A P Brezin, L Zhao, D W Gjertson, G N Holland, E F Reed, J H M Cohen, R Rajalingam
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  ABSTRACT: Birdshot chorioretinopathy (BCR), a chronic ocular inflammatory disease with characteristic choroidal lymphocytic infiltrates, has been strongly associated with human leukocyte antigen (HLA)-A29. Although HLA-A29 occurs frequently in all populations, BCR affects only a small percentage of HLA-A29-positive Caucasians, indicating additional susceptibility factors for BCR. Discovery of HLA class I-specific killer cell immunoglobulin-like receptors (KIR) led to a series of epidemiological studies implicating KIR-HLA gene combinations in disease. Here, we characterized KIR-HLA pairs in BCR patients and controls carrying HLA-A*29 as well as controls lacking HLA-A*29. KIR-HLA pairs implicated for weak inhibition (KIR2DL2/3+HLA-C1 and KIR3DL1+HLA-Bw4(T80)) in combination with activating KIR genes associated with autoimmunity (KIR2DS2, 2DS3 and 2DS4) augment the risk of developing BCR in HLA-A*29-positive individuals. The reciprocal association of strong inhibitory pairs (KIR3DL1+HLA-Bw4(I80) and KIR2DL1+HLA-C2) in combination with those implicated in protection from infection (KIR3DS1+HLA-Bw4(I80) and KIR2DS1+HLA-C2) was observed in HLA-A*29-negative controls. These results suggest that a profound effect of KIR2DS2/S3/S4 in the absence of strong inhibition may enhance the activation of natural killer cells and T-cell subsets against intraocular self-antigens, thereby contributing to pathogenesis of BCR.
  Genes and immunity 05/2008; 9(3):249-58. · 4.22 Impact Factor