KIR/HLA gene combinations influence susceptibility to B-cell chronic lymphocytic leukemia and the clinical course of disease

July 25, 2011

BlankKIR/HLA gene combinations influence susceptibility to B-cell chronic

lymphocytic leukemia and the clinical course of disease.

L Karabon, A Jedynak, S Giebel, D Wolowiec, M Kielbinski, D Woszczyk, K

Kapelko-Slowik, K Kuliczkowski, and I Frydecka

Tissue Antigens, August 1, 2011; 78(2): 129-138.

Department of Experimental Therapy, Institute of Immunology and Experimental

Therapy, Polish Academy of Sciences, Weigla Str., Wroclaw, Poland Department of

Bone Marrow Transplantation, Comprehensive Cancer Center, Sklodowska-Curie

Memorial Institute, Gliwice Branch, Wybrzeze Armii Krajowej, Gliwice, Poland

Department of Hematology, Neoplastic Diseases & Bone Marrow Transplantation,

Medical University Wroclaw, Pasterua Str., Wroclaw, Poland Department of

Hematology, State Hospital, Kosnego Str., Opole, Poland.

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.

PMID: 21726204

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