[Show abstract][Hide abstract] ABSTRACT: Certain genotypic combinations of killer-cell immunoglobulin-like receptors (KIR) and human leukocyte antigens (HLA) have been associated with favourable outcomes after exposure to human immunodeficiency virus in Caucasoid and African populations. Human immunodeficiency virus (HIV) infection is characterized by a rapid exhaustion of CD4 cells, which results in impaired cellular immunity. During this early phase of infection, it is thought that the natural killer (NK) cells represent the main effector arm of the host immune response to HIV. This study investigates whether KIR and HLA factors are associated to CD4 T cell numbers after HIV infection in Mexican mestizos as assessed at the time of initial medical evaluation and subsequent clinical follow-up. KIR and HLA-B gene carrier frequency differences were compared between groups of patients stratified by CD4 T cell numbers as assessed during their first medical evaluation (a point in time at which all patients were anti-retroviral therapy naïve). In addition, the influence that these genetic factors have on averaged historical CD4 cell counts in patients subjected to follow-up (mostly therapy-experienced) was also evaluated. Our results suggest a protective role for the HLA-Bw4 and KIR3D + Bw4 combination in both therapy-naïve and therapy-experienced patients. This report furthers our understanding on the way that immune genes modulate HIV disease progression in less-studied human populations such as the Mexican mestizos with a special focus on CD4 T cell number and behaviour.
[Show abstract][Hide abstract] ABSTRACT: Expansion of a natural killer (NK) cell population that expresses NKG2C has been associated with cytomegalovirus and other viral infections. It has been suggested that this cell population may play a role in infection control. Deletion of the NKG2C gene (homozygous or heterozygous) has been reported with high prevalence in European and Asian populations. However, the effect of NKG2C genotype on NK cell responses to infection remains poorly defined. We determined the prevalence of the NKG2C deletion in a Mexican population (n = 300) and in a group of patients (n = 131) to assess whether NKG2C genotype affects the incidence of symptomatic viral infections caused by influenza or respiratory syncytial virus. The frequency of the NKG2C deletion haplotype in Mexican mestizos was significantly lower (10.3%) than that reported in other populations (17.5-21.9%). No difference in the prevalence of NKG2C deletion was observed in subjects with viral infections compared with the reference population. In addition, no differences in clinical characteristics and infection outcome were observed between patients with and without the NKG2C gene deletion. Our results indicate that copy number variation in the NKG2C gene has no impact on the severity of respiratory viral infections.
International Journal of Immunogenetics 12/2013; 41(2). DOI:10.1111/iji.12104 · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: a b s t r a c t Killer-cell immunoglobulin-like receptors (KIR) are membrane proteins expressed by natural killer cells and CD8 lymphocytes. The KIR system consists of 17 genes and 614 alleles, some of which bind human leukocyte antigens (HLA). Both KIR and HLA modulate susceptibility to haematological malignancies, viral infections and autoimmune diseases. Molecular epidemiology studies employ traditional statistical methods to identify links between KIR genes and disease. Here we describe our results at applying artificial intelligence algorithms (support vector machines) to identify associations between KIR genes and disease. We demonstrate that these algorithms are capable of classifying samples into healthy and diseased groups based solely on KIR genotype with potential use in clinical decision support systems.
Computers in Biology and Medicine 09/2013; 43(1):2053-2062. DOI:10.1016/j.compbiomed.2013.09.027 · 1.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
A genetic association between osteoarthritis (OA) and a polymorphism in the aspartic acid (D) repeat of the asporin (ASPN) gene has been reported in Japanese, Han Chinese, Greek and UK Caucasian populations of patients having knee and hip OA. Such an association has not been previously described among the Mexican mestizo population. The aim of this study was to analyze the association of the ASPN gene D-repeat polymorphism in a Mexican mestizo population with primary knee OA as well as in healthy controls.
Materials and methods:
A case-control study was conducted on a Mexican mestizo population of northern Mexico. The repeat polymorphism was genotyped in 440 subjects (218 cases and 222 healthy controls). Primary knee OA was diagnosed according to American College of Rheumatology and Kellgren-Lawrence criteria, and allelic association was examined adjusting for other risk variables.
After adjusting for some covariates, menopause and the D16 allele showed a trend toward being risk factors for knee OA in a Mexican mestizo population. Also, the D12 allele could be considered as a protective factor.
These findings suggest that polymorphisms within the ASPN gene could influence knee OA susceptibility, but these associations must be confirmed by independent studies in larger samples and different ethnic groups to support the role of the D-repeat polymorphism in the ASPN gene as risk or protection factors for knee OA in a Mexican population.
[Show abstract][Hide abstract] ABSTRACT: Introduction of a novel influenza virus into the human population leads to the occurrence of pandemic events, such as the one caused by pandemic influenza A (H1N1) 2009 virus. The severity of infections caused by this virus in young adults was greater than that observed in patients with seasonal influenza. Fatal cases have been associated with an abnormal innate, proinflammatory immune response. A critical role for natural killer cells during the initial responses to influenza infections has been suggested. In this study, we assessed the association of killer-cell immunoglobulin-like receptors (KIRs) with disease severity by comparing KIR gene content in patients with mild and severe pandemic influenza virus infections to a control group. We found that activator (KIR3DS1 and KIR2DS5) and inhibitory (KIR2DL5) genes, encoded in group B haplotypes containing the cB01, cB03 and tB01 motifs, are associated with severe pandemic influenza A (H1N1) 2009 infections. Better understanding of how genetic variability contributes to influenza virus pathogenesis may help to the development of immune intervention strategies aiming at controlling the severity of disease.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To determine the prevalence of congenital cytomegalovirus infection in newborn infants included in the neonatal screening program coordinated by the State Health Services in San Luis Potosí. MATERIAL AND METHODS: We evaluated the presence of cytomegalovirus in blood samples stored in filter paper. RESULTS: Cytomegalovirus was detected in 10 (0.68%) of the 1 457 samples included in the study. There were no differences in the characteristics of infants with congenital infection compared to those without infection. CONCLUSIONS: It is necessary to increase awareness of health professionals regarding the prevalence and impact of congenital cytomegalovirus infection.
Salud publica de Mexico 12/2011; 53(6):513-515. DOI:10.1590/S0036-36342011000600007 · 0.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the prevalence of congenital cytomegalovirus infection in newborn infants included in the neonatal screening program coordinated by the State Health Services in San Luis Potosí.
We evaluated the presence of cytomegalovirus in blood samples stored in filter paper.
Cytomegalovirus was detected in 10 (0.68%) of the 1,457 samples included in the study. There were no differences in the characteristics of infants with congenital infection compared to those without infection.
It is necessary to increase awareness of health professionals regarding the prevalence and impact of congenital cytomegalovirus infection.
Salud publica de Mexico 12/2011; 53(6):513-5. · 0.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Natural killer (NK) cell function is regulated by different types of membrane-bound receptors of which killer-cell immunoglobulin-like receptors (KIRs) are the most complex and diverse. KIRs are encoded by 17 different genes located within the leukocyte receptor complex (19q13.4). The frequency with which KIR gene features are present in different human populations differs. Here, we present our results on the KIR gene diversity observed in a large group of mestizos from the central Mexican city of San Luis Potosí. In total, 53 different KIR genotypes were observed, 47 with previously described gene profiles and six harboring novel KIR gene combinations. Group A homozygous haplotypes were seen in 102 individuals (34%), while group B homozygous haplotypes were present in 45 (15%). Heterozygous combinations of groups A and B haplotypes were seen in 153 individuals (51%). Haplotype frequency estimations based on a true content of 600 chromosomes showed a relatively balanced proportion of group A (59.5%) and group B (40.5%) haplotypes in our study population. A homozygous combination of the cA01|tA01 haplotype was present in 33% of the population with other frequent combinations being cA01|tA01, cB03|tB01 in 14.7% and cA01|tA01, cB02|tA01 in 12%. The dendrogram derived from activating KIR gene phylogenetic analysis revealed five clearly distinct clades corresponding to African, East Asian, Arab/Caucasoid, Mexican mestizo/Amerindian and South Asian populations. Our results illustrate the genetic contribution that Caucasoid and Amerindian populations have made toward present-day Mexicans and suggest an important Southeast Asian genetic contribution to native Amerindian populations.
[Show abstract][Hide abstract] ABSTRACT: Acute respiratory infections are a leading cause of morbidity and mortality worldwide. Starting in 2009, pandemic influenza A(H1N1) 2009 virus has become one of the leading respiratory pathogens worldwide. However, the overall impact of this virus as a cause of mortality has not been clearly defined.
To determine the impact of pandemic influenza A(H1N1) 2009 on mortality in a Mexican population.
We assessed the impact of pandemic influenza virus on mortality during the first and second outbreaks in San Luis Potosí, Mexico, and compared it to mortality associated with seasonal influenza and respiratory syncytial virus (RSV) during the previous winter seasons.
We estimated that, on average, 8·1% of all deaths that occurred during the 2003-2009 seasons were attributable to influenza and RSV. During the first pandemic influenza A(H1N1) 2009 outbreak, there was an increase in mortality in persons 5-59 years of age, but not during the second outbreak (Fall of 2009). Overall, pandemic influenza A (H1N1) 2009 outbreaks had similar effects on mortality to those associated with seasonal influenza virus epidemics.
The impact of influenza A(H1N1) 2009 virus on mortality during the first year of the pandemic was similar to that observed for seasonal influenza. The establishment of real-time surveillance systems capable of integrating virological, morbidity, and mortality data may result in the timely identification of outbreaks so as to allow for the institution of appropriate control measures to reduce the impact of emerging pathogens on the population.
Influenza and Other Respiratory Viruses 03/2011; 5(2):76-82. DOI:10.1111/j.1750-2659.2010.00187.x · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epigenetic mechanisms are crucial to regulate the expression of different genes required for neuronal plasticity. Neurotoxic substances such as arsenic, which induces cognitive deficits in exposed children before any other manifestation of toxicity, could interfere with the epigenetic modulation of neuronal gene expression required for learning and memory. This study assessed in Wistar rats the effects that developmental arsenic exposure had on DNA methylation patterns in hippocampus and frontal cortex. Animals were exposed to arsenic in drinking water (3 and 36ppm) from gestation until 4 months of age, and DNA methylation in brain cells was determined by flow cytometry, immunohistochemistry and methylation-specific polymerase chain reaction (PCR) of the promoter regions of reelin (RELN) and protein phosphatase 1 (PP1) at 1, 2, 3 and 4 months of age. Immunoreactivity to 5 methyl-cytosine was significantly higher in the cortex and hippocampus of exposed animals compared to controls at 1 month, and DNA hypomethylation was observed the following months in the cortex at high arsenic exposure. Furthermore, we observed a significant increase in the non-methylated form of PP1 gene promoter at 2 and 3 months of age, either in cortex or hippocampus. In order to determine whether this exposure level is associated with memory deficits, a behavioral test was performed at the same age points, revealing progressive and dose-dependent deficits of fear memory. Our results demonstrate alterations of the methylation pattern of genes involved in neuronal plasticity in an animal model of memory deficit associated with arsenic exposure.
Neurochemistry International 02/2011; 58(5):574-81. DOI:10.1016/j.neuint.2011.01.020 · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the contribution of influenza and respiratory syncytial virus (RSV) as the cause of lower respiratory tract infection (LRTI) associated hospitalizations during the first year of the influenza A(H1N1) 2009 pandemic and to assess the severity of illness during the second pandemic wave.
Patients admitted with LRTI from April 2009 through March 2010 were assessed for the presence of influenza and RSV. Pandemic influenza virus was detected by means of a nested RT-PCR assay and/or the CDC's real time-PCR protocol. RSV was detected using a one-step RT-PCR assay. The characteristics of patients admitted during the first and second pandemic outbreaks were compared.
657 patients with LRTI were admitted during the study period. Pandemic influenza virus was detected in 180 and RSV in 133. Influenza was the most common cause of infection in adults, while RSV was more common in children. There were no differences in disease severity between the first and second pandemic outbreaks.
Pandemic influenza virus was associated to increased numbers of hospitalizations and deaths; particularly in adults. The severity of the first and second pandemic outbreaks was similar. RSV continues to be the main pathogen responsible for hospitalizations in young children.
The Journal of infection 11/2010; 61(5):382-90. DOI:10.1016/j.jinf.2010.08.008 · 4.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe the clinical characteristics and outcomes of adults hospitalized with pneumonia during the pandemic (H1N1) 2009 outbreak. Patients admitted to a general hospital in San Luis Potosí, Mexico, from April 10 through May 11, 2009, suspected to have influenza virus-associated pneumonia were evaluated. We identified 50 patients with suspected influenza pneumonia; the presence of influenza virus was confirmed in 18: 11 with pandemic (H1N1) 2009 virus, 5 with unsubtypeable influenza A virus, 1 with seasonal influenza A virus (H3N2), and 1 in whom assay results for seasonal and pandemic (H1N1) 2009 viruses were positive. Eighteen patients were treated in the intensive care unit, and 10 died. During the pandemic (H1N1) 2009 outbreak, severe pneumonia developed in young adults who had no identifiable risk factors; early diagnosis and treatment of influenza virus infections may have a determinant role in outcome.
[Show abstract][Hide abstract] ABSTRACT: One of the major factors that have contributed to improving the outcomes of Stem Cell Transplantation is progress made in the field of human leucocyte antigen(s) (HLA). This is evident not only in developing techniques for rapid and accurate tissue typing, but also in the greatly improved understanding of the HLA system and the impact of HLA matching on transplant complications. It is now accepted that high-resolution HLA matching for transplant recipients and unrelated donors is associated with the best clinical outcomes. The most important HLA determinants are the six 'classical' polymorphic HLA loci: HLA-A, -B, -C, -DRB1,-DQB1, -DPB1. For several years, based on the outcome of numerous studies, a 10/10 matched donor (HLA-A, -B, -C, -DRB1, -DQB1) was considered the ideal. The impact of HLA-DPB1 has been less clear, in view of reduced likelihood of patient/donor matching for this locus. More recently, several large studies have questioned the importance of HLA-DQB1 matching on outcome. Based on the findings of recent studies, the current gold standard unrelated donor is believed to be one matched for 8/8 alleles at high resolution i.e. matched for HLA-A, -B, -C, -DRB1, however, in certain circumstances, mismatches may be tolerated and/or permissive.
British Journal of Haematology 08/2010; 150(3):251-8. DOI:10.1111/j.1365-2141.2010.08224.x · 4.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human cytomegalovirus (hCMV) infection is usually asymptomatic but may cause disease in immunocompromised hosts. It has been reported that hCMV infection may shape the NK cell receptor (NKR) repertoire in adult individuals, promoting a variable expansion of the CD94/NKG2C+ NK cell subset. We explored the possible relationship between this viral infection and the expression pattern of different NKR including CD94/NKG2C, CD94/NKG2A, immunoglobulin-like transcript 2 (ILT2, CD85j), KIR2DL1/2DS1, KIR3DL1, and CD161 in peripheral blood lymphocytes from healthy children, seropositive (n=21) and seronegative (n=20) for hCMV. Consistent with previous observations in adults, a positive serology for hCMV was associated with increased numbers of NKG2C+ NK and T cells as well as with ILT2+ T lymphocytes. Moreover, the proportions of CD161+ and NKG2C+CD56-CD3- NK cells also tended to be increased in hCMV+ individuals. Excretion of the virus was associated with higher proportions of NKG2C+ NK cells. Altogether, these data reveal that hCMV may have a profound influence on the NKR repertoire in early childhood.
European Journal of Immunology 05/2010; 40(5):1418-27. DOI:10.1002/eji.200939898 · 4.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We analyzed 2378 respiratory samples of children <5 years of age admitted during a 7-year period in order to determine the contribution of seasonal influenza as a cause of hospitalizations, as well as the impact of the inclusion of influenza vaccine in the childhood immunization program. The presence of influenza virus was demonstrated in 106 (4.4%) samples. The proportion of influenza hospitalizations after the introduction of influenza vaccination was lower (3.4%) than before the establishment of this vaccination program (7.5%; P=0.00002). Our study shows that influenza vaccination programs in children significantly reduce the impact of influenza related hospitalizations.
[Show abstract][Hide abstract] ABSTRACT: Molecular epidemiology and genomic characterisation studies require the screening of large numbers of individuals to achieve statistical significance. Although many of the novel DNA extraction methods offer convenient, high-throughput capabilities, their use for the processing of larger sample volumes becomes very expensive. We are currently compiling the Mexican Genomic DNA Collection in order to address specific health priorities through molecular techniques. Our approach employs a low-cost laundry detergent based DNA extraction technique that maximizes DNA yield and quality. We have optimised four different modalities (maxiprep, midiprep, miniprep and microprep) for two different sources (leukocyte concentrates and whole blood). Our optimised protocol produces 4.5 mg of DNA from 15 ml of blood-bank discarded leukocyte concentrates with spectrophotometric quality, genomic integrity and PCR suitability that rivals that of phenol-chloroform extracted samples. We present evidence of many PCR applications that we have carried out on samples extracted with this technique including Killer-cell Immunoglobulin-like Receptor genotyping, Short Tandem Repeat profiling as well as nucleic acid screening for hepatitis B and human immunodeficiency type-1 viruses. This paper highlights many of the advantages that this DNA extraction technique provides over existing methodologies, whether it is used to establish large genomic DNA collections (as was our main intention) or as a routine DNA extraction method for PCR applications.
[Show abstract][Hide abstract] ABSTRACT: Introducción La influenza es una infección aguda de vías respiratorias causada por los virus de la influenza, la cual causa a nivel mundial entre 250 000 a 500 000 muertes anuales (50). En México se reportaron 7 200 muertes y 66 000 individuos que recibieron atención hospitalaria por complicaciones respiratorias en los años 2001 y 2002, respectivamente, entre individuos mayores a los 65 años de edad (26). Los virus de la influenza que generalmente infectan a los humanos corresponden a los géneros A, B y C; pertenecientes a la familia Orthomyxoviridae. El virus de la influenza A es el responsable de epidemias anuales durante el invierno lo cual ocasiona un incremento importante de ausentismo laboral así como en la demanda de consultas médicas (45). Así mismo, el influenzavirus A tiene la capacidad de ocasionar pandemias globales periódicas con un gran impacto económico, social y sanitario (27). El virus de la influenza A se clasifica en subtipos en base a la antigenicidad de las glicoproteínas de superficie hemaglutinina (HA) y neuraminidasa (NA). Actualmente, 16 subtipos de HA (1-16) y 9 de NA (1-9) son reconocidos (18). Los influenzavirus infectan a una gran variedad de animales incluyendo a humanos, cerdos, caballos, mamíferos marinos y aves. La mayoría de los subtipos virales se replican en las células intestinales de aves acuáticas sin causar enfermedad evidente (62).