KIR/HLA gene combinations influence susceptibility to B-cell chronic lymphocytic leukemia and the clinical course of disease.
KIR/HLA gene combinations influence susceptibility to B-cell chronic lymphocytic leukemia and the clinical course of disease.
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DOI：
10.1111/j.1399-0039.2011.01721.x
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发表时间：
2011-08
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通讯作者：
L. Karabon;A. Jedynak;S. Giebel;D. Wołowiec;M. Kiełbiński;D. Woszczyk;K. Kapelko-Słowik;K. Kuliczkowski;I. Frydecka
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作者：
L. Karabon;A. Jedynak;S. Giebel;D. Wołowiec;M. Kiełbiński;D. Woszczyk;K. Kapelko-Słowik;K. Kuliczkowski;I. Frydecka
本研究旨在分析B细胞免疫球蛋白样受体（KIR）及其人类白细胞抗原（HLA）配体基因多态性与慢性B细胞淋巴细胞白血病（B-CLL）易感性及临床病程的关系。197例B-CLL患者和200例对照组中单个KIR基因的分布相似，除了B-CLL患者中KIR 2DS 3和KIR 2DL 5基因的频率较低（26.9% vs 35.5%，P = 0.06，46.2% vs 55.5%，P = 0.06）。KIR 2DS 3与B-CLL之间的关联在女性中达到统计学显著性（P = 0.05）。此外，我们发现，与对照组相比，B-CLL患者中存在5个或6个激活KIR基因的基因型频率较低（20.8% vs 29.0%，P = 0.06），B-CLL患者中具有抑制性KIR基因的个体频率显著高于激活性KIR基因（比值< 0.71）（P = 0.04）。B-CLL患者HLA-Bw 4特异性显著降低（48.7%vs63.0%，P = 0.005），这是由于HLA-Bw 4（Thr 80）频率降低（21.6%vs32.0%，P = 0.02）所致。此外，在HLA-Bw 4阳性个体中，存在KIR 3DS 1的无进展生存期（PFS）倾向于更高（77% ± 9% vs 39% ± 13%，P = 0.07）。然而，在B-CLL患者中，HLA-C2的存在与PFS降低相关（49% ± 9% vs 75% ± 7%，P = 0.02），在HLA-C2阳性患者中，在不存在KIR 2DS 1的情况下，PFS的概率显著降低（34% ± 11% vs 77% ± 7%，P = 0.007）。我们的研究结果表明，抑制/激活KIR基因的模式，连同他们的HLA配体，与B-CLL的易感性，并影响这种疾病的临床过程。
The aim of this study was to analyze the association between gene polymorphisms of killer-cell immunoglobulin-like receptors (KIRs) and their human leukocyte antigen (HLA) ligands and susceptibility to B-cell chronic lymphocytic leukemia (B-CLL) and the clinical course of disease. The distribution of individual KIR genes in 197 B-CLL patients and 200 controls was similar, except for a tendency for lower frequencies of the KIR2DS3 and KIR2DL5 genes among B-CLL patients (26.9% vs 35.5%, P = 0.06, 46.2% vs 55.5%, P = 0.06). The associations between KIR2DS3 and B-CLL reached statistical significance in women (P = 0.05). Moreover, we found a trend toward a lower frequency of genotypes with the presence of five or six activating KIR genes in B-CLL patients compared to controls (20.8% vs 29.0%, P = 0.06), and a significantly higher frequency of individuals possessing genotypes with a prevalence of inhibitory over activating KIR genes (ratio < 0.71) among B-CLL patients (P = 0.04). The HLA-Bw4 specificity was significantly reduced among B-CLL patients (48.7% vs 63.0%, P = 0.005), which resulted from a decreased frequency of HLA-Bw4(Thr80) (21.6% vs 32.0%, P = 0.02). Moreover, among HLA-Bw4-positive individuals, progression-free survival (PFS) tended to be higher in the presence of KIR3DS1 (77% ± 9% vs 39% ± 13%, P = 0.07). However, in B-CLL patients, the presence of HLA-C2 was associated with decreased PFS (49% ± 9% vs 75% ± 7%, P = 0.02), and among HLA-C2-positive patients, the probability of PFS was significantly reduced in the absence of KIR2DS1 (34% ± 11% vs 77% ± 7%, P = 0.007). Our results indicate that the pattern of inhibitory/activating KIR genes, together with their HLA ligands, is associated with susceptibility to B-CLL and affects the clinical course of this disease.