PMID- 37454198
OWN - NLM
STAT- MEDLINE
DCOM- 20230717
LR  - 20231124
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 13
IP  - 1
DP  - 2023 Jul 15
TI  - Association of killer cell immunoglobulin-like receptors and their cognate HLA 
      class I ligands with susceptibility to acute myeloid leukemia in Iranian 
      patients.
PG  - 11456
LID - 10.1038/s41598-023-38479-x [doi]
LID - 11456
AB  - 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 Bw4(Ile80)( +) 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.
CI  - (c) 2023. The Author(s).
FAU - Mirzazadeh, Sara
AU  - Mirzazadeh S
AD  - Department of Immunology, Shiraz Medical School, Shiraz University of Medical 
      Sciences, Shiraz, Iran.
FAU - Bemani, Peyman
AU  - Bemani P
AD  - Department of Immunology, School of Medicine, Isfahan University of Medical 
      Sciences, Isfahan, Iran.
FAU - Halimi, Hossein
AU  - Halimi H
AD  - Department of Immunology, Shiraz Medical School, Shiraz University of Medical 
      Sciences, Shiraz, Iran.
FAU - Sanaee, Mohammad Nabi
AU  - Sanaee MN
AD  - Department of Hematology and Medical Oncology, Namazi Hospital, Shiraz University 
      of Medical Sciences, Shiraz, Iran.
FAU - Karami, Narges
AU  - Karami N
AD  - Department of Immunology, Shiraz Medical School, Shiraz University of Medical 
      Sciences, Shiraz, Iran.
FAU - Ramzi, Mani
AU  - Ramzi M
AD  - Department of Hematology and Medical Oncology, Namazi Hospital, Shiraz University 
      of Medical Sciences, Shiraz, Iran.
FAU - Farjadian, Shirin
AU  - Farjadian S
AD  - Department of Immunology, Shiraz Medical School, Shiraz University of Medical 
      Sciences, Shiraz, Iran. shirinenator@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230715
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Ligands)
RN  - 0 (Receptors, KIR)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-A Antigens)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Iran
MH  - Case-Control Studies
MH  - Ligands
MH  - *Receptors, KIR/genetics
MH  - HLA-B Antigens/genetics
MH  - HLA Antigens/genetics
MH  - Genotype
MH  - *Leukemia, Myeloid, Acute/genetics
MH  - HLA-A Antigens/genetics
PMC - PMC10349836
COIS- The authors declare no competing interests.
EDAT- 2023/07/16 01:06
MHDA- 2023/07/17 06:42
PMCR- 2023/07/15
CRDT- 2023/07/15 23:27
PHST- 2022/12/27 00:00 [received]
PHST- 2023/07/09 00:00 [accepted]
PHST- 2023/07/17 06:42 [medline]
PHST- 2023/07/16 01:06 [pubmed]
PHST- 2023/07/15 23:27 [entrez]
PHST- 2023/07/15 00:00 [pmc-release]
AID - 10.1038/s41598-023-38479-x [pii]
AID - 38479 [pii]
AID - 10.1038/s41598-023-38479-x [doi]
PST - epublish
SO  - Sci Rep. 2023 Jul 15;13(1):11456. doi: 10.1038/s41598-023-38479-x.