Distribution of killer immunoglobulin-like receptor genes in HIV infected long-term non-progressors from Mumbai, India

Background: Few reports suggest the association of killer immunoglobulin-like receptors of natural killer cells with human immunodeficiency virus infection. India with world's third largest population of human immunodeficiency virus / acquired immunodeficiency syndrome, offers scope to study such association. Objective: Current study (2010-2015) was designed to evaluate if killer immunoglobulin-like receptors gene polymorphisms are associated with HIV infection outcomes specifically, with long term non progressors. Methods: Killer immunoglobulin-like receptors genotyping was done using polymerase chain reaction - sequence-specific primer method. Viral load was measured by Cobas Taqman HIV-1 test. Estimation of CD4 counts was done using BD FACS CD4 count reagent. Results: The activating gene frequencies identified were 3DS1 (53.8%), 2DS3 (69.2%), 2DS4 (76.9%), 2DS5 (69.2%), 2DS1 (76.9%) and 2DS2 (92.3%). The inhibitory gene frequencies were 2DL2 (92.3%), 2DL5 (76.9%), 2DL3 (69.5%), 3DL1 (84.6%), 3DL2 (92.3%) and 2DL1 (100%). The results highlight high frequency of 3DS1/3DL1 heterozygote and killer immunoglobulin-like receptor 2DS1, among these long term non progressors indicating their possible association with slow progression. Genotype analysis shows total 13 genotypes, of which 8 genotypes were identified for the first time from India. Two genotypes were unique/novel, which were unreported. All genotypes observed in this study were considered to be Bx genotype (100 %). Limitations: A small sample size (n=13, due to a rare cohort) and the absence of control group were the limitations of this study. Conclusions: The present study highlights the distribution of killer immunoglobulin-like receptor genes in a very rare group of human immunodeficiency virus -1 infected individuals - long term non progressors. All the long term non progressors tested show the presence of Bx haplotype and each long term non progressors has a different killer immunoglobulin-like receptor genotype.

Características de atividade das células natural killer em pacientes com esclerose sistêmica / Characteristics of NK cell activity in patients with systemic sclerosis

INTRODUÇÃO: Estudos têm relatado um aumento da expressão das células natural killer (NK) no sangue periférico de pacientes com esclerose sistêmica (ES). Essas células fazem parte da imunidade inata, reconhecendo células infectadas por meio dos receptores killer immunoglobulin-like receptor (KIR), que apresentam acentuado polimorfismo. Um novo modelo foi proposto prevendo a atividade das células NK, avaliando o excesso de ativação (EA), excesso de inibição (EI) ou se a célula está funcionalmente em equilíbrio (balance, B) (neutra). OBJETIVO: Avaliar a atividade das células NK em pacientes com ES e comparar com grupo-controle. MÉTODO: Cento e dez pacientes com ES e 115 controles foram estudados. Foi aplicado um novo modelo que prevê a atividade das células NK. Para esse método, considerou-se cada célula com seu respectivo ligante KIR/HLA-C e Bw4. A nomenclatura utilizada foi EA, EI e B. RESULTADOS: Nossos resultados mostraram que 63,5% dos controles saudáveis apresentavam o fenótipo KIR caracterizado por EI, em comparação com 39,1% dos pacientes com ES (P = 0,001). Considerando-se somente indivíduos com presença de KIR2DL2 (KIR2DL2+), encontramos 34,7% de EI em controles sadios e 10,9% em pacientes com ES (P < 0,001). CONCLUSÃO: Em nosso estudo, o modelo que prevê a ação das células NK mostrou que controles sadios têm maior frequência de EI quando comparados a pacientes com ES, sugerindo um efeito protetor do EI contra o desenvolvimento da ES. Outros estudos, porém, devem ser realizados para confirmar nossos dados.

INTRODUCTION: Previous studies have shown an increased expression of natural killer (NK) cells in the peripheral blood of patients with systemic sclerosis (SSc). NK cells are part of innate immunity, recognizing infected cells through killer immunoglobulin-like receptors (KIR), which show marked polymorphism. A novel model has been proposed predicting the activity of NK cells, evaluating whether there is excessive activation (EA), excessive inhibition (EI) or balance (B) (neutral). OBJECTIVE: To evaluate the activity of NK cells in patients with SSc and compare it with that of a control group. METHOD: This study comprised 110 patients with SSc and 115 healthy controls. A novel model that predicts the activity of NK cells was used. For that, cells with their respective KIR/HLA-C and Bw4 ligands were considered. The activity of NK cells was defined as EA, EI, or B. RESULTS: Our results showed that 63.5% of healthy controls had the KIR phenotype characterized by EI, as compared with 39.1% of the patients with SSc (P = 0.001). Considering only KIR2DL2-positive individuals, 34.7% of EI was found in healthy controls and 10.9% in patients with SSc (P < 0.001). CONCLUSION: In our study, the model that predicts the action of NK cells showed that healthy controls have higher frequency of EI as compared with SSc patients, suggesting a protective effect of the EI profile against the development of SSc. These results suggest a potential role of NK cells in the pathogenesis of SSc, but further studies should be conducted to confirm our data.

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.

Progress on the killer immunoglobulin-like receptor in the acute rejection response with kidney transplantation / 国际外科学杂志

The success of organ transplantation depends on the prevetion of acute rejection. T and B lymphocytes, the major components of the cellular and humoral immunization mediating the rejection response, respectively, have been extensively studied. The importance of matural killer(NK) cells in transplantation has become an increasing area of interest as reagents for their study have become available. Basing on this on the killer immunoglobulin-like receptor in the acute rejection response with kidney transplantation.

Association of killer immunoglobulin-like receptors with leukemia / 第三军医大学学报

Objective To study the correlation between the genes of killer immunoglobulin (Ig)-like receptors (KIR) in natural killer cells and leukemia. MethodsPrimers of 16 KIR genes, including KIR2DL1-5, KIR3DL1-3, KIR2DS1-5, KIR3DS1 and 2 pseudogenes 2DP1 and 3DP1, were designed and synthesized. A polymerase chain reaction with sequence-specific primers (PCR-SSP) was developed to detect the mRNA expressions of the 16 genes. Totally 46 healthy individuals and 46 leukemic patients (15 cases of acute myelocytic leukemia, 13 cases of chronic myelocytic leukemia and 18 cases of acute lymphocytic leukemia) were detected and the frequencies of the KIR genes were analyzed. ResultsThe frequency of 2DL4, 3DL2, 3DL3 and 2DP1 in healthy and leukemic patients were 100%, and were detected in all patients and healthy individuals. The other KIR genes had similar frequencies except those of 2DL2 and 2DS2, which were 47.8% of the healthy individuals and 89.1% in leukemic patients. There was a significant difference between the 2 groups.ConclusionThere may be an association between pathogenesis of leukemia and 2DL2 and 2DS2 genes.