KIR repertory in patients with hematopoietic diseases and healthy family members

Since the discovery of specific histocompatibility, literature has associated genes involved in the immune response, like the Human Leucocyte Antigen (HLA), with a better prognosis in transplantation. However, other non-HLA genes may also influence the immune process, such as the genes encoding the immunoglobulin-like receptors of natural killer cells (KIRs). The discovery that NK cell KIR receptors interact with conservative epitopes (C1, C2, Bw4) presented in HLA class I molecules that are genetically polymorphic, also observed in KIR genes, led to the investigation of the relevance of the KIR system to hematopoietic stem cell transplant. The cure of patients with leukemias and other hematological malignancies after bone marrow transplantation (BMT) has been attributed in part to the ability of the donor immune cells, present in the graft, to recognize and eliminate neoplastic cells of the patient. The cytotoxic activity of NK cells is mediated by the absence of HLA class I-specific ligands on the target cell surface to inhibitory KIR receptors (hypothesis of “missing-self”).

We analyzed, by PCR typing-SSOP technique, the presence or absence of 16 KIR genes and haplotypes of 39 patients with hematopoietic disorders and 136 healthy individuals from Paraná State. The comparisons made between the patient and control group were performed using χ² test or Fisher exact test (bilateral p-value), as appropriated. Significance level was considered when p-value ≤ 0.05.

Framework genes KIR3DL3, KIR3DP1, KIR2DL4 and KIR3DL2 were positive in all samples. The comparison between KIR repertoire of patients and healthy individuals revealed significant differences (p < 0.05) in inhibitors genes KIR2DL2 (p = 0.0005) and KIR2DL5 (p = 0.0067) and activating genes KIR2DS1 (p = 0.0013), KIR2DS2 (p = 0.0038), KIR2DS3 (p = 0.0153) that are more frequent in controls than in patients. The KIR2DS3 was significantly more frequent (p = 0.0031) in patients with acute myeloid leukemia (AML) when compared to patients with acute lymphoblastic leukemia (ALL). We observed a higher frequency of haplotype A (59 %) in the patients.

Our data suggests that susceptibility to leukemia can be influenced, at least, partly byKIR receptors.