Resistance of KIR Ligand–Missing Leukocytes to NK Cells In Vivo in Patients with Acquired Aplastic Anemia

Abstract

The loss of killer cell Ig-like receptor ligands (KIR-Ls) due to the copy number-neutral loss of heterozygosity of chromosome 6p (6pLOH) in leukocytes of patients with acquired aplastic anemia (AA) may alter the susceptibility of the affected leukocytes to NK cell killing in vivo. We studied 408 AA patients, including 261 who were heterozygous for KIR-Ls, namely C1/C2 or Bw6/Bw4, for the presence of KIR-L-missing [KIR-L(2)] leukocytes. KIR-L(2) leukocytes were found in 14 (5.4%, C1 [n = 4], C2 [n = 3], and Bw4 [n = 7]) of the 261 patients, in whom corresponding KIR(+) licensed NK cells were detected. The incidence of 6pLOH in the 261 patients (18.0%) was comparable to that in 147 patients (13.6%) who were homozygous for KIR-L genes. The percentages of HLA-lacking granulocytes (0.8-50.3%, median 15.2%) in the total granulocytes of the patients with KIR-L(2) cells were significantly lower than those (1.2-99.4%, median 55.4%) in patients without KIR-L(2) cells. KIR2DS1 and KIR3DS1 were only possessed by three of the 14 patients, two of whom had C2/C2 leukocytes after losing C1 alleles. The expression of the KIR3DS1 ligand HLA-F was selectively lost on KIR-L(2) primitive hematopoietic stem cells derived from 6pLOH(+) induced pluripotent stem cells in one of the KIR3DS1(+) patients. These findings suggest that human NK cells are able to suppress the expansion of KIR-L(2) leukocytes but are unable to

Exploration of KIR genes and hematological-related diseases in Chinese Han population

“…Moreover, it has been shown that KIR genotypes and cytokines, as well as cytokine receptor gene SNPs, may play a role in the important susceptibility to excessive and/or reduced immune response 28 , 29 . For instance, expression of the KIR3DS1 ligand HLA-F is selectively lost on KIR-L (-) primitive hematopoietic stem cells derived from 6pLOH (+) induced pluripotent stem cells in KIR3DS1 (+) patients 30 . And Zeng et al found an association between toll-like receptor genes in bone marrow CD4+ cells and overexpression of KIR genes in bone marrow CD8+ cells in AA patients 31 .…”

Exploration of KIR Genes and Hematological-related Diseases in Chinese Han Population: a Multi-center Retrospective Analysis

“…Moreover, it has been shown that KIR genotypes and cytokines, as well as cytokine receptor gene SNPs, may play a role in the important susceptibility to excessive and/or reduced immune response [28][29] . For instance, expression of the KIR3DS1 ligand HLA-F is selectively lost on KIR-L (-) primitive hematopoietic stem cells derived from 6pLOH (+) induced pluripotent stem cells in KIR3DS1(+) patients 30 . And Zeng et al found an association between toll-like receptor genes in bone marrow CD4 + cells and overexpression of KIR genes in bone marrow CD8 + cells in AA patients 31 .…”