Base teórica: A sepse é uma síndrome heterogênea, definida como disfunção orgânica que ameaça à vida, causada por uma resposta desregulada do hospedeiro à infecção. É um problema de saúde mundial, graças à sua alta prevalência, morbimortalidade associada, além de custos para seu tratamento. As células Natural Killer (NK) fazem parte do sistema imune inato reconhecendo moléculas de HLA de classe I em células alvo, através de seus receptores de membrana killer cell immunoglobulin-like receptors (KIR). A intensidade da resposta à infecção pode variar entre indivíduos, logo pode-se considerar que esta seja determinada por bases genéticas, e estas influenciem na ocorrência de sepse e variabilidade nos desfechos. Objetivos: Avaliar a associação entre os genes KIR e os ligantes HLA em pacientes críticos, comparando pacientes com sepse e controles não sépticos internados na mesma UTI. Métodos: Foi examinado o polimorfismo de 16 genes KIR e seus ligantes HLA em 271 pacientes críticos, caucasóides, sendo 211 pacientes com sepse e 60 controles, pela técnica de PCR-SSO e PCR-SSP, respectivamente. Resultados: Os genes ativadores KIR2DS1 e KIR3DS1 foram mais frequentes nos controles que nos pacientes com sepse (41,23% versus 55,00%, e 36,49% versus 51,67%; p = 0.041 e 0,025, respectivamente). Estes resultados fornecem informação inicial sobre o papel de polimorfismos de KIR na sepse, sugerindo que este possa ser um potencial marcador diagnóstico ou prognóstico da doença. / Background: Sepsis is a heterogeneous syndrome, defined a life-threatening organic dysfunction caused by a dysregulated host response to infection. Sepsis is a global health problem, due to its high prevalence, associated morbidity and mortality, and costs for its treatment. Cells Natural Killer (NK) cells are part of the innate immune system that recognize HLA class I molecules on target cells via membrane receptors called killer cell immunoglobulin-like receptors (KIR). The intensity of the response to an infection may vary among individuals and might be influenced genetic features affecting sepsis occurrence and variability in outcomes. Objectives: To evaluate the association between KIR genes and HLA ligands in critically ill patients, comparing patients with sepsis and without sepsis admitted to the same ICU. Methods: We examined the polymorphism of 16 KIR genes and their HLA ligands in 271 critically ill patients, Caucasians, and 211 patients with sepsis and 60 controls by PCR-SSO and PCR-SSP, respectively. Results: Activating KIR2DS1 and KIR3DS1 genes were more common in controls than in patients with sepsis (41.23% versus 55.00% and 36.49% versus 51.67%, p = 0.041 and 0.025, respectively). These results provide initial information on the role of polymorphism of KIR in sepsis, suggesting that this may be a potential diagnostic or prognostic marker of the disease.

Base teórica: A sepse é uma síndrome heterogênea, definida como disfunção orgânica que ameaça à vida, causada por uma resposta desregulada do hospedeiro à infecção. É um problema de saúde mundial, graças à sua alta prevalência, morbimortalidade associada, além de custos para seu tratamento. As células Natural Killer (NK) fazem parte do sistema imune inato reconhecendo moléculas de HLA de classe I em células alvo, através de seus receptores de membrana killer cell immunoglobulin-like receptors (KIR). A intensidade da resposta à infecção pode variar entre indivíduos, logo pode-se considerar que esta seja determinada por bases genéticas, e estas influenciem na ocorrência de sepse e variabilidade nos desfechos. Objetivos: Avaliar a associação entre os genes KIR e os ligantes HLA em pacientes críticos, comparando pacientes com sepse e controles não sépticos internados na mesma UTI. Métodos: Foi examinado o polimorfismo de 16 genes KIR e seus ligantes HLA em 271 pacientes críticos, caucasóides, sendo 211 pacientes com sepse e 60 controles, pela técnica de PCR-SSO e PCR-SSP, respectivamente. Resultados: Os genes ativadores KIR2DS1 e KIR3DS1 foram mais frequentes nos controles que nos pacientes com sepse (41,23% versus 55,00%, e 36,49% versus 51,67%; p = 0.041 e 0,025, respectivamente). Estes resultados fornecem informação inicial sobre o papel de polimorfismos de KIR na sepse, sugerindo que este possa ser um potencial marcador diagnóstico ou prognóstico da doença. / Background: Sepsis is a heterogeneous syndrome, defined a life-threatening organic dysfunction caused by a dysregulated host response to infection. Sepsis is a global health problem, due to its high prevalence, associated morbidity and mortality, and costs for its treatment. Cells Natural Killer (NK) cells are part of the innate immune system that recognize HLA class I molecules on target cells via membrane receptors called killer cell immunoglobulin-like receptors (KIR). The intensity of the response to an infection may vary among individuals and might be influenced genetic features affecting sepsis occurrence and variability in outcomes. Objectives: To evaluate the association between KIR genes and HLA ligands in critically ill patients, comparing patients with sepsis and without sepsis admitted to the same ICU. Methods: We examined the polymorphism of 16 KIR genes and their HLA ligands in 271 critically ill patients, Caucasians, and 211 patients with sepsis and 60 controls by PCR-SSO and PCR-SSP, respectively. Results: Activating KIR2DS1 and KIR3DS1 genes were more common in controls than in patients with sepsis (41.23% versus 55.00% and 36.49% versus 51.67%, p = 0.041 and 0.025, respectively). These results provide initial information on the role of polymorphism of KIR in sepsis, suggesting that this may be a potential diagnostic or prognostic marker of the disease.

Base teórica: A sepse é uma síndrome heterogênea, definida como disfunção orgânica que ameaça à vida, causada por uma resposta desregulada do hospedeiro à infecção. É um problema de saúde mundial, graças à sua alta prevalência, morbimortalidade associada, além de custos para seu tratamento. As células Natural Killer (NK) fazem parte do sistema imune inato reconhecendo moléculas de HLA de classe I em células alvo, através de seus receptores de membrana killer cell immunoglobulin-like receptors (KIR). A intensidade da resposta à infecção pode variar entre indivíduos, logo pode-se considerar que esta seja determinada por bases genéticas, e estas influenciem na ocorrência de sepse e variabilidade nos desfechos. Objetivos: Avaliar a associação entre os genes KIR e os ligantes HLA em pacientes críticos, comparando pacientes com sepse e controles não sépticos internados na mesma UTI. Métodos: Foi examinado o polimorfismo de 16 genes KIR e seus ligantes HLA em 271 pacientes críticos, caucasóides, sendo 211 pacientes com sepse e 60 controles, pela técnica de PCR-SSO e PCR-SSP, respectivamente. Resultados: Os genes ativadores KIR2DS1 e KIR3DS1 foram mais frequentes nos controles que nos pacientes com sepse (41,23% versus 55,00%, e 36,49% versus 51,67%; p = 0.041 e 0,025, respectivamente). Estes resultados fornecem informação inicial sobre o papel de polimorfismos de KIR na sepse, sugerindo que este possa ser um potencial marcador diagnóstico ou prognóstico da doença. / Background: Sepsis is a heterogeneous syndrome, defined a life-threatening organic dysfunction caused by a dysregulated host response to infection. Sepsis is a global health problem, due to its high prevalence, associated morbidity and mortality, and costs for its treatment. Cells Natural Killer (NK) cells are part of the innate immune system that recognize HLA class I molecules on target cells via membrane receptors called killer cell immunoglobulin-like receptors (KIR). The intensity of the response to an infection may vary among individuals and might be influenced genetic features affecting sepsis occurrence and variability in outcomes. Objectives: To evaluate the association between KIR genes and HLA ligands in critically ill patients, comparing patients with sepsis and without sepsis admitted to the same ICU. Methods: We examined the polymorphism of 16 KIR genes and their HLA ligands in 271 critically ill patients, Caucasians, and 211 patients with sepsis and 60 controls by PCR-SSO and PCR-SSP, respectively. Results: Activating KIR2DS1 and KIR3DS1 genes were more common in controls than in patients with sepsis (41.23% versus 55.00% and 36.49% versus 51.67%, p = 0.041 and 0.025, respectively). These results provide initial information on the role of polymorphism of KIR in sepsis, suggesting that this may be a potential diagnostic or prognostic marker of the disease.

In Canada, and more specifically in Canadian-born Aboriginals and foreign born populations, high incidence of tuberculosis (TB) causes significant morbidity and mortality. The presence or absence of specific killer immunoglobulin-like receptor (KIR) genes, individually or in conjunction, may be associated with tuberculosis (active, latent, or uninfected disease status) as well as ethnicity of an individual. It is hypothesized that the differences in KIR profiles, gene frequencies, and/or haplotypes in Canadian-born Aboriginal, Canadian-born non-Aboriginal, and foreign born individuals elicits a differential activation or inhibition profile, resulting in differential cytokine expression and eventually contributes to the outcome of TB infection. In this study we examined the enrichment or depletion of KIR genes in different ethnic populations in Manitoba with special focus on active, latent, and uninfected TB status. In addition, we sought to explore the statistical correlation between TB status and inhibitory/stimulatory KIR haplotypes.

In Canada, and more specifically in Canadian-born Aboriginals and foreign born populations, high incidence of tuberculosis (TB) causes significant morbidity and mortality. The presence or absence of specific killer immunoglobulin-like receptor (KIR) genes, individually or in conjunction, may be associated with tuberculosis (active, latent, or uninfected disease status) as well as ethnicity of an individual. It is hypothesized that the differences in KIR profiles, gene frequencies, and/or haplotypes in Canadian-born Aboriginal, Canadian-born non-Aboriginal, and foreign born individuals elicits a differential activation or inhibition profile, resulting in differential cytokine expression and eventually contributes to the outcome of TB infection. In this study we examined the enrichment or depletion of KIR genes in different ethnic populations in Manitoba with special focus on active, latent, and uninfected TB status. In addition, we sought to explore the statistical correlation between TB status and inhibitory/stimulatory KIR haplotypes.

Inwardly rectifying potassium (IRK/Kir) channels regulate intracellular K+ concentrations and membrane potential. Disruption of Kir2.1 causes dominantly inherited Andersen Tawil Syndrome (ATS). ATS patients suffer from cardiac arrhythmias, periodic paralysis, and cognitive impairment. These symptoms are consistent with current understanding of the role of ion channels in muscle cells and neurons. However, ATS symptoms also include craniofacial and digital deformities such as cleft palate, dental defects, wide set eyes, low set ears, and crooked or fused digits. These developmental defects were not consistent with current understanding of developmental signaling or previously described roles for ion channels. We found that phenotypes exhibited by the Kir2.1 knockout mouse recapitulate ATS symptoms. The Kir2.1 knockout mouse phenotypes are strikingly similar to those that occur when Transforming Growth Factor β/Bone Morphogenetic Protein (TGFβ/BMP) signaling is disrupted. Based on this observation, we hypothesized that Kir2.1 may play a role in TGFβ/BMP signaling. We tested this hypothesis using Drosophila melanogaster. We reduced a Kir2.1 homologue Irk2 by siRNA, eliminated the Irk2 channel with a deficiency, and abolished heteromeric Irk channel function with a dominant negative Irk2. Reduction of Irk2 function caused wing patterning defects and size reduction that are similar to BMP/Decapentaplegic (DPP) mutant phenotypes. Ubiquitous expression of Irk2DN is lethal. Wing specific Irk2DN expression caused severe defects compared to irk2Df demonstrating that Irk channels are heteromeric. We found that two downstream targets of Dpp were reduced in irk2Df and siRNA expressing wing discs showing that Dpp requires Irk2 activity. We found that wing specific expression of Irk2DN completely prevents Mad phosphorylation and induces apoptosis. Suppression of apoptosis does not rescue MAD phosphorylation showing that apoptosis is caused by lack of an external signal. We systemically tested the components of the Dpp signaling cascade to find at what point in Dpp signaling Irk2 is required. We found that Irk2 is not directly required for the intracellular propagation of the Dpp signal. Irk2DN could not eliminate the phosphorylation of Mad by a constitutively activated Tkv. We showed that Irk2 affects Dpp spread across the disc. We speculate that Irk2 affects the endocytic pathway that transports Dpp from medial cells to lateral cells. We tested the impact of irk2DN on the development of the Drosophila eye where Irk2 is expressed and Dpp is required for normal patterning. We found that abolition of Irk channels causes eye defects that are similar to those that occur with the loss of Dpp signaling. Trachea development also depends on Dpp. Blocking Irk2 in the developing trachea results in severe defects. We conclude that Irk2 plays a global role in Dpp signaling. Kir/Irk channels could be therapeutic targets to treat diseases that are impacted by TGFβ/BMP signaling, such as cancer. Furthermore, the demonstration that Irk2 is a node for BMP-like signaling could be used to control cell fate decisions for regenerative medicine or stem cell therapeutics.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2015-07-23T16:56:03Z No. of bitstreams: 1 Igor Ives Santos Fraga Associação... 2014.pdf: 1141300 bytes, checksum: 79bef8840226ef6a639a9c8c9e118161 (MD5) / Approved for entry into archive by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2015-07-23T16:56:29Z (GMT) No. of bitstreams: 1 Igor Ives Santos Fraga Associação... 2014.pdf: 1141300 bytes, checksum: 79bef8840226ef6a639a9c8c9e118161 (MD5) / Made available in DSpace on 2015-07-23T16:56:29Z (GMT). No. of bitstreams: 1 Igor Ives Santos Fraga Associação... 2014.pdf: 1141300 bytes, checksum: 79bef8840226ef6a639a9c8c9e118161 (MD5) Previous issue date: 2014 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / O controle da carga proviral do HTLV-1 depende em parte da lise de células infectadas por células citotóxicas mediada pelos linfócitos T CD8⁺ e pelas células NK (Natural killer). A família de receptores KIR (killer-cell immunoglobulin-like receptor) interage com as moléculas de HLA de classe I, principalmente os alelos do HLA C do grupo 1 (C*01, C*03, C*07, C*08, C*12, C*13, C*14 e C*16), ativando ou inibindo a função destas células.O objetivo do presente estudo foi avaliar se os genes KIR2DL2/KIR2DL3 e os alelos de HLA-C do grupo 1 estão associados ao controle da carga proviral do HTLV-1 e ao diagnóstico de HAM/TSP. O estudo foi realizado no Centro de HTLV da Escola Bahiana de Medicina e Saúde Púbica, em Salvador-Bahia. A presença dos genes KIR2DL2 e KIR2DL3 foi determinada por PCR em tempo real (Syber Green). Foram incluídos 248 indivíduos infectados pelo HTLV-1 (161 assintomáticos e 87 com HAM/TSP) cujos alelos de HLA de classe I haviam sido previamente determinados. A carga proviral (quantificada por PCR em tempo real) e as frequências de indivíduos assintomáticos e com diagnóstico de HAM/TSP (Possível, Provável e Definido) foram comparadas de acordo com a presença ou ausência dos genes KIR avaliados. As frequências dos genes KIR2DL2 e KIR2DL3 foi 84,3% e 96,8%, respectivamente. Não foram observadas diferenças estatisticamente significantes na frequência de indivíduos que possuíam os genes (KIR2DL2 ou KIR2DL3) nos grupos clínicos, assim como na frequência de indivíduos que tinham simultaneamente os genes KIR e os alelos de HLA-C do grupo 1. Os indivíduos do grupo HAM/TSP possível que apresentavam o gene KIR2DL2 tinham menor carga proviral (2,9% de células infectadas) que os indivíduos sem este gene (19,2% de células infectadas) (p<0,001). Quando avaliamos a combinação da presença do gene KIR2DL2 com os alelos de HLA-C do grupo 1, menor carga proviral (2,1%) foi observada nos indivíduos que apresentavam algum dos alelos de HLA-C do grupo 1,comparados aqueles que portavam apenas KIR2DL2 (5,0%) (p=0,013). Menor carga proviral também foi observada nos indivíduos assintomáticos que portavam simultaneamente o gene KIR2DL2 e o alelo HLA-C*07, comparados aos indivíduos com apenas o gene KIR2DL2 (p=0,03), enquanto que os indivíduos com HAM/TSP-PB que tinham essa combinação (KIR2DL2/HLA-C*07) apresentaram tendência de menor carga proviral (p=0,051). Em conclusão, a presença da combinação do gene KIR2DL2 e de algum alelo de HLA-C do grupo 1 está associada ao controle da carga proviral. Este estudo quantificou pela primeira vez as frequências de genes KIR em uma coorte de indivíduos infectados pelo HTLV-1 do estado da Bahia. Estudos futuros são necessários para confirmar estes achados em outras populações e avaliar o valor prognóstico da associação de KIR2DL2 e HLA-C do grupo 1. / The control of proviral load of HTLV-1 depends in part of the lysis of infected cells mediated by cytotoxic CD8⁺T lymphocytes and NK (Natural killer) cells. The family of KIR (killer-cell immunoglobulin-like receptor) interacts with HLA class I molecules, especially those HLA-C alleles in-group 1 (C*01, C*03, C*07, C*08, C*12, C*13, C*14 and C*16) by activating or inhibiting the function of these cells. The aim of this study was to evaluate if the KIR2DL2, KIR2DL3 genes and group 1 HLA-C alleles are associated with the control of proviral load of HTLV-1 and the diagnosis of HAM/TSP. The study was performed at Bahiana School HTLV Center of Medicine and Health Public, in Salvador, Bahia. The presence of KIR2DL2 and KIR2DL3 genes was determined by real-time PCR (Syber Green). The study included 248 subjects infected with HTLV-1(161 and 87 asymptomatic with HAM/TSP) whose HLA class I alleles were previously determined. The proviral load (quantified by real-time PCR) and the frequency asymptomatic individuals diagnosed with HAM/TSP (possibly, probably and definitive) were compared according to the presence or absence of KIR genes evaluated. The frequencies of KIR2DL2 and KIR2DL3 genes were 84.3% and 96.8%, respectively. No statistically significant differences were observed in the frequency of individuals who possessed the genes (KIR2DL2 or KIR2DL3) in clinical groups, as well as the frequency of individuals who had both the KIR genes and HLA-C alleles group 1. Individuals in the group HAM/TSP possible to KIR2DL2 showed that the gene had lower proviral load (2.9%of cells infected) individuals without this gene (19.2% infected cells) (p<0.001). When we evaluated the combination of the presence of KIR2DL2 and 2DL3 genes with HLA-C genes in group 1, lower proviral load (2.1%) was observed in individuals with any of the alleles of HLA-C group 1, compared who those which harbored only KIR2DL2 (5.0%) (p=0.013) .Minor proviral load was also observed in asymptomatic individuals which carried both the KIR2DL2 gene and HLA-C*07 allele when compared to individuals with only KIR2DL2 gene (p=0.03), whereas patients with HAM/TSP-PB that had this combination (KIR2DL2/HLA-C*07) tended to lower proviral load(p=0.051). In conclusion, the presence of the combination of KIR2DL2 gene and a HLA-C group1allele is associated with proviral load control. This study quantified for the first time the frequencies of KIR genes in a cohort of individuals infected with HTLV-1 in Bahia. Future studies are needed to confirm these findings in other populations and to evaluate the prognostic value of KIR2DL2 association and HLA-C group 1.

Background. O nascimento pré-termo permanece sendo grande causa de mortalidade neonatal. A vulnerabilidade dos prematuros se dá principalmente pelas freqüentes intervenções médicas e por sua imaturidade imunológica. As infecções neonatais aumentam a probabilidade de complicações e prolongam o tempo de internação, aumentando o risco de mortalidade. A atividade das células Natural Killer (NK) em recém-nascidos prematuros está reduzida e associada com maior susceptibilidade a agentes infecciosos. As células NK são capazes de mediar a resposta do sistema imune inato contra células infectadas por vírus e células malignas transformadas, podendo provocar um ataque direto às células alvo. Os principais receptores das células NK são os KIR ou killer immunoglobulin-likereceptors que reconhecem moléculas de HLA classe I. Objetivo. Investigar o polimorfismo dos genes KIR e HLA de classe I nos recémnascidos pré-termos de muito baixo peso em comparação com recém-nascidos a termo. Métodos. Foram genotipados 154 recém-nascidos, 60 pré-termo e 94 a termo, para 16 genes KIR e seus ligantes HLA pelos métodos PCR SSO e PCR SSP, respectivamente. Resultados. Há diferença estatísticamente significativa (P<0.0001) entre recémnascidos pré-termo e a termo para o gene KIR2DS4, sendo menos freqüente no grupo de recém-nascidos pré-termos. Conclusões. A menor frequência do KIR2DS4 evidencia uma imunidade natural deficiente nesse grupo de recém-nascidos prematuros. / Background. Preterm birth remains a major a cause of neonatal mortality. Preterm infants are particularly vulnerable because of frequent medical intervention and an immature immune system. Neonatal infections increase the likelihood of complications and prolong hospital stay, increasing the risk of mortality. The activity of natural killer (NK) cells is reduced in preterm neonates and associated with increased susceptibility to infectious agents. NK cells are capable of mediating the innate immune response to virally infected cells and malignantly transformed cells, which might lead to a direct attack on target cells. Killer-cell immunoglobulin-like receptors (KIR) are the main NK cell receptors, and are known to recognize Human Leukocyte Antigen (HLA) class I molecules. Objective. To investigate polymorphisms of KIR and HLA class I genes in very low birth weight preterm neonates compared with full-term neonates. Methods. 154 neonates, 60 preterm and 94 full-term, were genotyped for 16 KIR genes and their HLA ligands by PCR-SSO and PCR-SSP respectively. Results. There was a statistically significant difference (P<0.0001) between preterm and full-term neonates for the KIR2DS4 gene, which was less frequent in preterm neonates. Conclusions. The lower frequency of KIR2DS4 indicates a deficient innate immune response in the group of preterm neonates.

Background. O nascimento pré-termo permanece sendo grande causa de mortalidade neonatal. A vulnerabilidade dos prematuros se dá principalmente pelas freqüentes intervenções médicas e por sua imaturidade imunológica. As infecções neonatais aumentam a probabilidade de complicações e prolongam o tempo de internação, aumentando o risco de mortalidade. A atividade das células Natural Killer (NK) em recém-nascidos prematuros está reduzida e associada com maior susceptibilidade a agentes infecciosos. As células NK são capazes de mediar a resposta do sistema imune inato contra células infectadas por vírus e células malignas transformadas, podendo provocar um ataque direto às células alvo. Os principais receptores das células NK são os KIR ou killer immunoglobulin-likereceptors que reconhecem moléculas de HLA classe I. Objetivo. Investigar o polimorfismo dos genes KIR e HLA de classe I nos recémnascidos pré-termos de muito baixo peso em comparação com recém-nascidos a termo. Métodos. Foram genotipados 154 recém-nascidos, 60 pré-termo e 94 a termo, para 16 genes KIR e seus ligantes HLA pelos métodos PCR SSO e PCR SSP, respectivamente. Resultados. Há diferença estatísticamente significativa (P<0.0001) entre recémnascidos pré-termo e a termo para o gene KIR2DS4, sendo menos freqüente no grupo de recém-nascidos pré-termos. Conclusões. A menor frequência do KIR2DS4 evidencia uma imunidade natural deficiente nesse grupo de recém-nascidos prematuros. / Background. Preterm birth remains a major a cause of neonatal mortality. Preterm infants are particularly vulnerable because of frequent medical intervention and an immature immune system. Neonatal infections increase the likelihood of complications and prolong hospital stay, increasing the risk of mortality. The activity of natural killer (NK) cells is reduced in preterm neonates and associated with increased susceptibility to infectious agents. NK cells are capable of mediating the innate immune response to virally infected cells and malignantly transformed cells, which might lead to a direct attack on target cells. Killer-cell immunoglobulin-like receptors (KIR) are the main NK cell receptors, and are known to recognize Human Leukocyte Antigen (HLA) class I molecules. Objective. To investigate polymorphisms of KIR and HLA class I genes in very low birth weight preterm neonates compared with full-term neonates. Methods. 154 neonates, 60 preterm and 94 full-term, were genotyped for 16 KIR genes and their HLA ligands by PCR-SSO and PCR-SSP respectively. Results. There was a statistically significant difference (P<0.0001) between preterm and full-term neonates for the KIR2DS4 gene, which was less frequent in preterm neonates. Conclusions. The lower frequency of KIR2DS4 indicates a deficient innate immune response in the group of preterm neonates.

Background. O nascimento pré-termo permanece sendo grande causa de mortalidade neonatal. A vulnerabilidade dos prematuros se dá principalmente pelas freqüentes intervenções médicas e por sua imaturidade imunológica. As infecções neonatais aumentam a probabilidade de complicações e prolongam o tempo de internação, aumentando o risco de mortalidade. A atividade das células Natural Killer (NK) em recém-nascidos prematuros está reduzida e associada com maior susceptibilidade a agentes infecciosos. As células NK são capazes de mediar a resposta do sistema imune inato contra células infectadas por vírus e células malignas transformadas, podendo provocar um ataque direto às células alvo. Os principais receptores das células NK são os KIR ou killer immunoglobulin-likereceptors que reconhecem moléculas de HLA classe I. Objetivo. Investigar o polimorfismo dos genes KIR e HLA de classe I nos recémnascidos pré-termos de muito baixo peso em comparação com recém-nascidos a termo. Métodos. Foram genotipados 154 recém-nascidos, 60 pré-termo e 94 a termo, para 16 genes KIR e seus ligantes HLA pelos métodos PCR SSO e PCR SSP, respectivamente. Resultados. Há diferença estatísticamente significativa (P<0.0001) entre recémnascidos pré-termo e a termo para o gene KIR2DS4, sendo menos freqüente no grupo de recém-nascidos pré-termos. Conclusões. A menor frequência do KIR2DS4 evidencia uma imunidade natural deficiente nesse grupo de recém-nascidos prematuros. / Background. Preterm birth remains a major a cause of neonatal mortality. Preterm infants are particularly vulnerable because of frequent medical intervention and an immature immune system. Neonatal infections increase the likelihood of complications and prolong hospital stay, increasing the risk of mortality. The activity of natural killer (NK) cells is reduced in preterm neonates and associated with increased susceptibility to infectious agents. NK cells are capable of mediating the innate immune response to virally infected cells and malignantly transformed cells, which might lead to a direct attack on target cells. Killer-cell immunoglobulin-like receptors (KIR) are the main NK cell receptors, and are known to recognize Human Leukocyte Antigen (HLA) class I molecules. Objective. To investigate polymorphisms of KIR and HLA class I genes in very low birth weight preterm neonates compared with full-term neonates. Methods. 154 neonates, 60 preterm and 94 full-term, were genotyped for 16 KIR genes and their HLA ligands by PCR-SSO and PCR-SSP respectively. Results. There was a statistically significant difference (P<0.0001) between preterm and full-term neonates for the KIR2DS4 gene, which was less frequent in preterm neonates. Conclusions. The lower frequency of KIR2DS4 indicates a deficient innate immune response in the group of preterm neonates.