Association of killer cell immunoglobulin-like receptors and their cognate HLA class I ligands with susceptibility to acute myeloid leukemia in Iranian patients.

Acute myeloid leukemia (AML) is one of the most prevalent leukemia in adults. Among the various NK receptors, killer immunoglobulin-like receptors (KIRs) carry out indispensable roles in NK cell development and function through engaging with class I human leukocyte antigens (HLA-I) as their ligands. Besides divergent KIR and HLA loci, KIR/HLA-I combinations have a significant effect on NK cell response. In this case-control study, we aimed to verify the association of KIR/HLA-I combinations with susceptibility to AML in the Southwestern Iranian population. KIR and HLA genotyping was performed with PCR-SSP by some novel primers for 181 patients with AML and 181 healthy controls. According to our results, the frequencies of KIR3DS1 (p = 0.0001, OR = 2.32, 95% CI 1.51-3.58), KIR2DS4fl (p = 0.02, OR = 1.53, 95% CI 1.05-2.21), CxT4 genotypes (p = 0.03, OR = 2.0, 95% CI 1.05-3.82), and T4 gene cluster (p = 0.01, OR = 1.99, 95% CI 1.17-3.41) were significantly higher in patients than controls, while C1/C2 genotype (p = 0.00002, OR = 0.39, 95% CI 0.25-0.61), HLA-A Bw4 (p = 0.02, OR = 0.6, 95% CI 0.38-0.94), and HLA-A*11 (p = 0.03, OR = 0.57, 95% CI 0.34-0.95) alleles were more frequent in controls. In addition, inhibitory (i)KIR/HLA-I combinations analysis revealed higher frequencies of KIR2DL1( +)/HLA-C2( +), KIR2DL2/3( +)/HLA-C1( +), KIR3DL1( +)/HLA-A Bw4( +), and KIR3DL2( +)/HLA-A*03/11( +) in the control group (p = 0.002, OR = 0.49, 95% CI 0.3-0.78; p = 0.04, OR = 0.62, 95% CI 0.39-0.99; p = 0.04, OR = 0.63, 95% CI 0.4-0.99; and p = 0.03, OR = 0.62, 95% CI 0.4-0.95, respectively). Overall, the number of iKIR/HLA-I combinations was more in the control group. Moreover, KIR3DS1( +)/HLA-B Bw4Ile80( +) and the sum of HLA-B Bw4/A Bw4 combined with KIR3DS1 as activating KIR/HLA-I combinations were more frequent among patients than controls (p = 0.01, OR = 1.99, 95% CI 1.14-3.49 and p = 0.005, OR = 1.97, 95% CI 1.22-3.19, respectively). In conclusion, our results postulate that inhibitory combinations play a protective role against AML by developing potent NK cells during education. It is noteworthy that KIR/HLA-I combination studies can be applicable in donor selection for allogeneic NK cell therapy in hematological malignancies.

Soluble CD138/Syndecan-1 Increases in the Sera of Patients with Moderately Differentiated Bladder Cancer.

BACKGROUND: CD138/Syndecan-1 (Sdc-1) is expressed on the tumor and stromal cells of invasive bladder carcinoma. CD138/Sdc-1 shedding from the cell surface is associated with the invasive phenotype in lung and breast cancers. PATIENTS AND METHODS: Soluble CD138/Sdc-1 was measured in the sera of 86 bladder cancer patients and 57 healthy individuals by a commercial ELISA assay. RESULTS: Soluble Sdc-1 was increased in the sera of patients with bladder cancer (138.42 ± 81.85 vs. 86.48 ± 82.58 ng/ml, p = 0.0003). Patients aged over 70 years had higher levels of CD138/Sdc-1 in their sera (159.7 ± 15.77 vs. 124.5 ± 9.99 ng/ml, p = 0.025), and soluble Sdc-1 levels were higher in the sera of patients with moderately differentiated tumors compared to poorly differentiated ones (170.47 ± 85.06 vs. 101.79 ± 68.24 ng/ml, p = 0.01). The soluble Sdc-1 level was higher in muscle-invasive (154.45 ± 83.60 vs. 89.9 ± 55.02 ng/ml) but not lymphatic-invasive (106.25 ± 52.10 vs. 123.43 ± 63.76 ng/ml) tumors (p = 0.027 and 0.45, respectively). A non-significant trend of soluble Sdc-1 increase in the sera of male patients compared to female patients was observed (145.38 ± 85.47 vs. 110.20 ± 59.04 ng/ml, p = 0.054). CONCLUSION: The elevated levels of soluble CD138/Sdc-1 in older bladder cancer patients and those with muscular invasion sheds some light on the mechanisms of the disease invasion.