Importance of killer immunoglobulin-like receptors in allogeneic hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA) compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients) can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein.

Recipient's Killer Cell Immunoglobulin-like Receptor Genotype and Human Leukocyte Antigen C Ligand Influence the Clinical Outcome following Living Donor Liver Transplantation

PURPOSE: The design of this study was to determine the most influential factor(s) on post-transplant immunological consequences, particularly with regard to the role of killer cell immunoglobulin-like receptors (KIRs) and their ligands (type I human leukocyte antigen (HLA)) in unstable liver function. METHODS: Retrospectively collected data from 319 recipients undergoing adult living donor liver transplantation (LDLT) using a right lobe graft between January 2002 and August 2008 were analyzed. Patients were categorized according to the serum alanine transaminase (ALT) pattern; stable ALT pattern was defined as ALT pattern during 3 months post-transplantation, except for initial 2 weeks post-transplantation, in which 2 times or less additional elevation(s) of serum alanine transaminase (ALT) (> or =80 IU/L) were observed. When a serum ALT pattern showed fluctuating and/or unpredictable nature, it was defined as an unstable pattern. In addition, genetic information of KIRs and HLA-C allotypes received from 68 recipients and 59 donors was analyzed by way of polymerase chain reaction using sequence-specific primers (PCR-SSP) to determine the factor(s) influencing a serum ALT pattern. RESULTS: Among 319 LDLT recipients included in this study, the actual incidences of AR and unstable ALT pattern were 13.4% (43/319) and 42.3% (135/319), respectively. Unstable ALT pattern correlated with poorer survival following LDLT than stable pattern (P<0.000). Genetically, unstable ALT pattern was related to recipients carrying KIR2DL2(+)/KIR2DS2(+) combined with the heterogeneous HLA-C allotype (HLA-C1/C2), (relative risks 45.0, 95% confidence interval 2.160~937.321; P=0.013). CONCLUSION: This study indicates that, when performing LDLT, pretransplant determination of recipient's KIRs and HLA-C allotypes may be beneficial in coping with post-transplant immunological circumstances.

The distribution of killer immunoglobulin-like receptor genes in Qingdao Han population / 中国输血杂志

Objective To investigate the distribution of killer immunoglobulin-like receptor(KIR) genes in Qingdao Han population and its difference from other populations.Methods The KIR genotypes of 81 cascs were examined by PCR-SSP,and the gene frequencies were calculated and compared to those of other populations.Result Fourteen KIR genes and 2 pseudo genes were found and all had different gene frequencies.Conclusion All inhibit-gene frequencies are higher than their active-gene frequencies.KIR gene frequencies are different between the southern and northern Chinese Han people.Many of them increase gradually from the south to the north.The KIR gene distributions of Korean and Japanese populations are close to the Northern Chinese Han population.

Antitumor effect of allogeneic NK cells on human multi-drug resistant nasopharyngeal carcinoma cells subcutaneously transplanted in BALB/c nude mice / 中国肿瘤生物治疗杂志

Objective:To study the inhibitory effect of allogeneic natural killer(NK) cells on subcutaneously transplanted human multi-drug resistant nasopharyngeal carcinoma cells(CNE2/DDP) in BALB/c nude mice.Methods:Human leucocyte antigen(HLA) genotypes of CNE2/DDP cells and the genotypes of inhibitory killer cell immunoglobulin-like receptor(KIR) in NK cells(isolated from 3 healthy persons by immuno-magnetic microbead technique) were analyzed by PCR-SSP.Twelve BALB/c nude mice were evenly divided into 2 groups:the control group and the treatment group.Mice in the treatment group were injected subcutaneously with 1?106 CNE2/DDP cells together with 3?107 NK cells via the tail veins;mice in the control group were injected with 1?106 CNE2/DDP cells subcutaneously.The tumor formation time,tumor formation rate and changes of tumor size were observed.Three weeks after tumor formation,all the mice were killed and human NK cells in peripheral blood were analyzed by flow cytometry;the tumors were weighed and the tumor inhibitory rates were calculated.Results:The HLA genotypes of CNE2/DDPcells were A2,24,B18,35,Cw4,and 7;the KIR genotypes of the 3 healthy persons were KIR2DL1,KIR2DL3,KIR3DL1,and KIR3DL2.There were mismatches between the KIRs expressed in NK cells and HLA class Ⅰ molecules expressed in the CNE2/DDP cells.NK cells obviously inhibited the growth of CNE2/DDP xenograft in nude mice.The tumor formation periods of control group and NK cell group were(17.17?1.17) d and(24.83?1.47) d,respectively(P

The gene frequencies of HLA-Cw in Guangdong Han population and its significance / 中国免疫学杂志

Objective:To explore the gene frequencies of HLA-Cw and to analyze the recognition characteristic between HLA-Cw and KIR in Guangdong Han population.Methods:An auto semi-quantitative PCR-RSSO method was adopted to detect the HLA-Cw genotypes of a sample of 122 bone marrow donors.Results:The gene frequencies of HLA-CW 03,07,01,08,04,14,15,12,06,05,16 were 0.237 1 , 0.215 9 , 0.175 2 , 0.112 9 , 0.050 5 , 0.041 9 , 0.041 9 , 0.037 6 , 0.033 3 , 0.008 2 , 0.004 1 respectively.HLA-Cw 02,04,05,06 belong to “group 1” recognizing KIR-2DL1/2DS1.HLA-Cw 01,03,07,08 belong to “group 2” recognizing KIR-2DL2/2DL3;2DS2/2DS3.There was a significant difference between the two groups in total HLA-Cw gene frequencies in Guangdong Han population( P