Abstract 4402

Introduction

Dysfunction in cellular and humoral immunity entails an increased risk of B-cell chronic lymphocytic leukemia (B-CLL). It has been suggested that innate immunity, especially natural killers cells play key role in antitumor cytotoxicity regulated by interaction between killer immunoglobulin-like receptors (KIRs) on NK cells and some T-cell subpopulations and their HLA-class I ligands on target cells. KIRs receptors have been divided into two functional groups: with long cytoplasmic tails (DL) - inhibitory and with short cytoplasmic tails (DS) - activating. Two broad haplotypes of KIR genes have been defined: the A haplotype characterized by presence of single activating KIR gene (2DS4) and the B haloptype characterized by two or more activating KIR genes (2DS1, 2DS2, 2DS3, 2DS5 and 3DS1).The 2DL2, 2DL3 and 2DS2 KIRs bind to HLA-C1 allotype (Asp80), while 2DL1 and 2DS1 KIRs bind to HLA-C2 allotype (Lys80). Due to lack of representative data in literature the study was undertaken to determine the association between polymorphism of KIR genes and HLA-C allotypes and susceptibility to B-CLL.

Patients and methods

The following KIR genes were typed: 2DL1, 2DL2, 2DL3, 3DL1, 2DS1, 2DS2, 2DS3, 2DS4fl, 2DS4del, 2DS5, 3DS1, in 200 B-CLL patients and 199 healthy individuals using PCR-SSP method. The HLA-C1 and HLA-C2 were determined using Olerup SSP typing kit in 187 B-CLL patients and 104 controls.

Results

Individual KIR gene content was similar in B-CLL cases and healthy controls although patients with KIR2DS3 gene were more common among cases compared to controls (36% vs. 27%, p=0.06) (Table1). The frequency of AA haplotype did not differ between studied groups (29% vs. 28%). Moreover no differences were found between incidence of HLA-C allotypes (HLA-C1: 74.3% vs. 76.0%, HLA-C2: 67.4% vs.70.2%), genotypes (C1/C1: 32.6% vs 29.8%, C1/C2: 41.7% vs 46,2% and C2/C2: 25.7% vs 24.1) and KIR genes in combination with genes for their HLA-C ligands in B-CLL patients and controls (Table 2).

Table 1.

Frequency of KIR genes in B-CLL patients and controls.

2DL12DL22DL32DS12DS22DS32DS4del2DS4fl2DS53DL13DS1
B-CLL (n=200) 195 106 176 75 108 54 166 56 53 186 70 
[%] 97.5 53.0 88.0 37.5 54.0 27.0 83.0 28.0 26.5 93.0 35.0 
Controls (n=199) 197 106 180 81 111 71 162 58 61 181 78 
[%] 99.0 53.3 90.5 40.7 55.8 35.7 81.4 29.1 30.7 91.0 39.2 
2DL12DL22DL32DS12DS22DS32DS4del2DS4fl2DS53DL13DS1
B-CLL (n=200) 195 106 176 75 108 54 166 56 53 186 70 
[%] 97.5 53.0 88.0 37.5 54.0 27.0 83.0 28.0 26.5 93.0 35.0 
Controls (n=199) 197 106 180 81 111 71 162 58 61 181 78 
[%] 99.0 53.3 90.5 40.7 55.8 35.7 81.4 29.1 30.7 91.0 39.2 
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Table.2.

Frequency of the KIR-HLA gene combinations in B-CLL patients and controls.

B-CLL (n = 187)
Controls (n = 104)
N%N%
2DL1+/C2+ 122 65.24 73 70.19 
2DL2/3+/C1+ 139 74.33 79 75.96 
2DS1+/C2+ 49 26.20 24 23.08 
2DS2+/C1+ 71 37.97 40 38.46 
2DL1+/C2- 60 32.08 30 28.80 
2DL2/3+/C1- 48 25.69 25 24.04 
2DS1+/C2- 22 11.76 18 17.31 
2DS2+/C1- 19 10.37 11 10.58 
B-CLL (n = 187)
Controls (n = 104)
N%N%
2DL1+/C2+ 122 65.24 73 70.19 
2DL2/3+/C1+ 139 74.33 79 75.96 
2DS1+/C2+ 49 26.20 24 23.08 
2DS2+/C1+ 71 37.97 40 38.46 
2DL1+/C2- 60 32.08 30 28.80 
2DL2/3+/C1- 48 25.69 25 24.04 
2DS1+/C2- 22 11.76 18 17.31 
2DS2+/C1- 19 10.37 11 10.58 
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Conclusions

The data obtain in this study imply that there may be not direct association between KIR and HLA-C gene content in the genome and the presence of B-CLL.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
chronic b-cell leukemias, chronic lymphocytic leukemia, genes, hla-c antigens, ligands, polish, human leukocyte antigens, cytotoxicity, functional group, polymerase chain reaction

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2009 by The American Society of Hematology
2009
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