Inhibitory killer cell immunoglobulin-like KIR3DL1 in combination with HLA-B Bw4[iso] protect against ankylosing spondylitis

The HLA class I molecules serve as ligands for both T cell receptors and killer cell immunoglobulin-like receptors [KIRs]. We investigated the HLA-C and HLA-Bw4 alleles as well as KIRs expression on CD56 positive lymphocytes to evaluate whether these genes and molecules could influence Ankylosing spondylitis [AS] susceptibility, alone or in combination. We typed 40 AS patients and 40 normal controls for HLA-C asn[80] [group 1] and HLA-C lys[80] [group 2], HLA-B Bw4[thero], HLA-B Bw4[iso] and HLA-A Bw4 alleles by PCR-SSP method. We also assessed the expression of KIR2DL1/2DS1, KIR2DL2/2DL3, KIR3DLI and KIR2DS4 by flow cytometry. The Pearson chi-square or Fisher exact test was performed for statistical analysis. The frequency of HLA-B Bw4[iso] but not HLA-B Bw4[thero] and HLA-A Bw4, ligand for the inhibitory KIR3DL1, was significant reduced in AS patients as compared with controls [p<0.01]. No significant differences were observed in gene carrier frequencies of HLA-C group 1 and 2 between AS and controls. Although no differences were found in the expression of KIR receptors between AS and normal was reduced in patients with AS compared to healthy controls [p<0.009]. We conclude that HLA-B Bw4[iso], the ligand of inhibitory KIR3DL1, with and without the expression of KIR3DL1 might be involved in protection against AS. Our results suggest that besides the HLA and KIR genotype, expression levels of KIRs may be involved in the pathogenesis of AS disease

KIR2DS3 is associated with protection against acute myeloid leukemia

Interaction between killer cell immunoglobulin-like receptors [KIR] and human leukocyte antigen [HLA] class I molecules is important for regulation of natural killer [NK] cell function. The aim of this study was to investigate the impact of compound KIR-HLA genotype on susceptibility to acute leukemia. Cohorts of Iranian patients with acute myeloid leukemia [AML; n=40] and acute lymphoid leukemia [ALL; n=38] were genotyped for seventeen KIR genes and their three major HLA class I ligand groups [C1, C2, Bw4] by a combined polymerase chain reaction-sequence-specific primers [PCR-SSP] assay. The results were compared with those of 200 healthy control individuals. We found a significantly decreased frequency of KIR2DS3 in AML patients compared to control group [12.5% vs. 38%, odds ratio=0.23, p=0.0018]. Also, the KIR3DS1 was less common in AML group than controls [27.5% vs. 44.5%, p=0.0465, not significant after correction]. Other analyses including KIR genotypes, distribution and balance of inhibitory and activating KIR+HLA combinations, and co-inheritance of activating KIR genes with inhibitory KIR+HLA pairs were not significantly different between leukemia patients and the control group. However, in AML patients a trend toward less activating and more inhibitory KIR-HLA state was observed. Interestingly, this situation was not found in ALL patients and inhibition enhancement through increase of HLA ligands and inhibitory combinations was the main feature in this group. Our findings may suggest a mechanism for escape of leukemic cells from NK cell immunity