RESUMEN
BACKGROUND: Seroepidemiological studies provide estimates of population-level immunity, prevalence/incidence of infections, and evaluation of vaccination programs. We assessed the seroprevalence of protective antibodies against influenza and evaluated the correlation of seroprevalence with the cumulative annual influenza incidence rate. METHODS: We conducted an annual repeated cross-sectional seroepidemiological survey, during June-August, from 2014 to 2019, in Portugal. A total of 4326 sera from all age groups, sex, and regions was tested by hemagglutination inhibition assay. Seroprevalence and geometric mean titers (GMT) of protective antibodies against influenza were assessed by age group, sex, and vaccine status (65+ years old). The association between summer annual seroprevalence and the difference of influenza incidence rates between one season and the previous one was measured by Pearson correlation coefficient (r). RESULTS: Significant differences in seroprevalence of protective antibodies against influenza were observed in the population. Higher seroprevalence and GMT for A(H1N1)pdm09 and A(H3N2) were observed in children (5-14); influenza B seroprevalence in adults 65+ was 1.6-4.4 times than in children (0-4). Vaccinated participants (65+) showed significant higher seroprevalence/GMT for influenza. A strong negative and significant correlation was found between seroprevalence and ILI incidence rate for A(H1N1)pdm09 in children between 5 and 14 (r = -0.84; 95% CI, -0.98 to -0.07); a weak negative correlation was observed for A(H3N2) and B/Yamagata (r ≤ -0.1). CONCLUSIONS: The study provides new insight into the anti-influenza antibodies seroprevalence measured in summer on the ILI incidence rate in the next season and the need for adjusted preventive health care measures to prevent influenza infection and transmission.
Asunto(s)
Anticuerpos Antivirales , Gripe Humana , Humanos , Estudios Seroepidemiológicos , Estudios Transversales , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Gripe Humana/inmunología , Femenino , Masculino , Adulto , Incidencia , Anticuerpos Antivirales/sangre , Preescolar , Niño , Persona de Mediana Edad , Adolescente , Adulto Joven , Anciano , Portugal/epidemiología , Lactante , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/inmunología , Pruebas de Inhibición de Hemaglutinación , Virus de la Influenza B/inmunología , Estaciones del Año , Recién Nacido , Anciano de 80 o más AñosRESUMEN
Familial articular chondrocalcinosis (CC) was first reported in 1963. It is characterised by multiple calcifications of hyaline and fibrous cartilage in the joints and intervertebral discs. Mutations in ANKH have been identified in several pedigrees as a monogenic cause for this disorder. ANKH is a key protein in pyrophosphate metabolism and is involved in pyrophosphate transport across the cell membrane. The objective of this work was to screen ANKH and ENPP1, two key genes in pyrophosphate metabolism, in Slovakian kindreds with familial CC. DNA samples from 25 individuals (10 affected, 15 unaffected) from 8 families were obtained. The promoter, coding regions and intron-exon boundaries of ANKH and ENPP1 were sequenced. Twelve DNA sequence variants, six in each gene, were identified. All the variants had been previously identified. None segregated with the disease. Our results suggest that neither ANKH nor ENPP1 mutations are the cause of CC in these families, indicating that possibly other major genes are involved in the aethiopathogenesis of this condition in these families.
Asunto(s)
Condrocalcinosis/etnología , Condrocalcinosis/genética , Mutación/genética , Proteínas de Transporte de Fosfato/genética , Hidrolasas Diéster Fosfóricas/genética , Pirofosfatasas/genética , Condrocalcinosis/epidemiología , Difosfatos/metabolismo , Exones/genética , Femenino , Frecuencia de los Genes/genética , Humanos , Intrones , Masculino , Linaje , Fenotipo , Eslovaquia/epidemiologíaRESUMEN
This report describes a 32-year-old woman presenting since childhood with progressive calcium pyrophosphate disease (CPPD), characterized by severe arthropathy and chondrocalcinosis involving multiple peripheral joints and intervertebral disks. Because ANKH mutations have been previously described in familial CPPD, the proband's DNA was assessed at this locus by direct sequencing of promoter and coding regions and revealed 3 sequence variants in ANKH. Sequences of exon 1 revealed a novel isolated nonsynonymous mutation (c.13 C>T), altering amino acid in codon 5 from proline to serine (CCG>TCG). Sequencing of parental DNA revealed an identical mutation in the proband's father but not the mother. Subsequent clinical evaluation demonstrated extensive chondrocalcinosis and degenerative arthropathy in the proband's father. In summary, we report a novel mutation, not previously described, in ANKH exon 1, wherein serine replaces proline, in a case of early-onset severe CPPD associated with metabolic abnormalities, with similar findings in the proband's father.
Asunto(s)
Condrocalcinosis/genética , Hipofosfatemia Familiar/genética , Mutación/genética , Proteínas de Transporte de Fosfato/genética , Adulto , Antirreumáticos/uso terapéutico , Pirofosfato de Calcio/orina , Condrocalcinosis/diagnóstico por imagen , Condrocalcinosis/tratamiento farmacológico , Condrocalcinosis/orina , Quimioterapia Combinada , Femenino , Glucocorticoides/uso terapéutico , Supresores de la Gota/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico , Linaje , Prednisolona/uso terapéutico , RadiografíaRESUMEN
Diffuse Idiopathic Skeletal Hyperostosis (DISH) and Ossification of the Posterior Longitudinal Ligament (OPLL) are common disorders characterized by the ossification of spinal ligaments. The cause for this ossification is currently unknown but a genetic contribution has been hypothesized. Over the last decade, many studies on the genetics of ectopic calcification disorders have been performed, mainly on OPLL. Most of these studies were based on linkage analysis and case control association studies. Animal models have provided some clues but so far, the involvement of the identified genes has not been confirmed in human cases. In the last few years, many common variants in several genes have been associated with OPLL. However, these associations have not been at definitive levels of significance and evidence of functional significance is generally modest. The current evidence suggests a multifactorial aetiopathogenesis for DISH and OPLL with a subset of cases showing a stronger genetic component.
RESUMEN
HLA class I diversity (loci A, B and C) was analysed in four populations, two from North Cameroon (Podokwo and Uldeme) and two from South Cameroon (Ewondo and Bamileke). Northern and southern Cameroon populations show a substantial genetic diversity in terms of haplotype sharing and genetic distances, even despite the low percentage of variance due to differences among populations evidenced by analysis of molecular variance. The signals of differentiation among populations are consistent with their linguistic affiliation, and support previous evidence, based on autosomal microsatellites and protein loci, which has shown that the complex pattern of genetic variation of Cameroon can in part be described by contrasting the northern and southern part of the country. Looking at our results in the more general framework of HLA diversity in sub-Saharan Africa, it turns out that the Podokwo and Uldeme show some genetic links to populations of the southern western branch of the Sahel corridor, while their high frequency of A*02 and C*04 alleles is congruent with previously hypothesised introgression of non-sub-Saharan alleles. On the other hand, signals of shared ancestry between the Bamileke and Ewondo and the Bantu speakers from central and southern Africa were detected.
Asunto(s)
Población Negra/genética , Genes MHC Clase I , Variación Genética , África del Sur del Sahara/etnología , África Austral/etnología , Camerún , Frecuencia de los Genes , Haplotipos , HumanosRESUMEN
OBJECTIVES: DISH/CC is a poorly understood phenotype characterised by peripheral and axial enthesopathic calcifications, frequently fulfilling the radiological criteria for Diffuse Idiopathic Skeletal Hyperostosis (DISH, MIM 106400), and in some cases associated with Calcium Pyrophosphate Dihydrate (CPPD) Chondrocalcinosis (CC). The concurrence of DISH and CC suggests a shared pathogenic mechanism. In order to identify genetic variants for susceptibility we performed whole exome sequencing in four patients showing this phenotype. MATERIALS AND METHODS: Exome data were filtered in order to find a variant or a group of variants that could be associated with the DISH/CC phenotype. Variants of interest were subsequently confirmed by Sanger sequencing. Selected variants were screened in a cohort of 65 DISH/CC patients vs 118 controls from Azores. The statistical analysis was performed using PLINK V1.07. RESULTS: We identified 21 genetic variants in 17 genes that were directly or indirectly related to mineralization, several are predicted to have a strong effect at a protein level. Phylogenetic analysis of altered amino acids indicates that these are either highly conserved in vertebrates or conserved in mammals. In case-control analyses, variant rs34473884 in PPP2R2D was significantly associated with the DISH/CC phenotype (p=0.028; OR=1.789, 95% CI= 1.060 - 3.021)). CONCLUSION: The results of the present and preceding studies with the DISH/CC families suggests that the phenotype has a polygenic basis. The PPP2R2D gene could be involved in this phenotype in an as yet unknown way.
Asunto(s)
Condrocalcinosis/genética , Secuenciación del Exoma , Hiperostosis Esquelética Difusa Idiopática/genética , Adulto , Condrocalcinosis/complicaciones , Femenino , Humanos , Hiperostosis Esquelética Difusa Idiopática/complicaciones , MasculinoRESUMEN
The authors describe the main clinical and radiological findings of common enthesopathic disorders-spondylarthritis (SpA), chondrocalcinosis/calcium pyrophosphate dehydrate crystal deposition disease (CPPD CDD) and diffuse idiopathic skeletal hyperostosis (DISH), stressing similarities and differences which may help in the differential diagnosis. They emphasize the clinical presentation of the "pseudoankylosing spondylitis" forms of CPPD CDD. They also review the most relevant genes and molecular mechanisms associated with these conditions and with another enthesopathic disorder with high prevalence in the Japanese population-ossification of the posterior longitudinal ligament (OPLL).
Asunto(s)
Condrocalcinosis/diagnóstico por imagen , Condrocalcinosis/patología , Hiperostosis Esquelética Difusa Idiopática/diagnóstico por imagen , Hiperostosis Esquelética Difusa Idiopática/patología , Espondiloartritis/diagnóstico por imagen , Espondiloartritis/patología , Animales , Calcinosis , Condrocalcinosis/genética , Condrocalcinosis/fisiopatología , Diagnóstico Diferencial , Predisposición Genética a la Enfermedad , Humanos , Hiperostosis Esquelética Difusa Idiopática/genética , Hiperostosis Esquelética Difusa Idiopática/fisiopatología , Osificación del Ligamento Longitudinal Posterior/diagnóstico por imagen , Osificación del Ligamento Longitudinal Posterior/genética , Osificación del Ligamento Longitudinal Posterior/patología , Osificación del Ligamento Longitudinal Posterior/fisiopatología , Radiografía , Espondiloartritis/genética , Espondiloartritis/fisiopatologíaRESUMEN
INTRODUCTION: Respiratory syncytial virus (RSV) is associated with substantial morbidity and mortality since it is a predominant viral agent causing respiratory tract infections in infants, young children and the elderly. Considering the availability of the RSV vaccines in the coming years, molecular understanding in RSV is necessary. OBJECTIVE: The objective of the present study was to describe RSV epidemiology and genotype variability in Portugal during the 2014/15-2017/18 period. MATERIAL AND METHODS: Epidemiological data and RSV-positive samples from patients with a respiratory infection were collected through the non-sentinel and sentinel influenza surveillance system (ISS). RSV detection, subtyping in A and B, and sequencing of the second hypervariable region (HVR2) of G gene were performed by molecular methods. Phylogenetic trees were generated using the Neighbor-Joining method and p-distance model on MEGA 7.0. RESULTS: RSV prevalence varied between the sentinel (2.5%, 97/3891) and the non-sentinel ISS (20.7%, 3138/16779), being higher (Pâ¯<â¯0.0001) among children aged <5 years. Bronchiolitis (62.9%, 183/291) and influenza-like illness (24.6%, 14/57) were associated (Pâ¯<â¯0.0001) with RSV laboratory confirmation among children aged <6 months and adults ≥65 years, respectively. The HVR2 was sequenced for 562 samples. RSV-A (46.4%, 261/562) and RSV-B (53.6%, 301/562) strains clustered mainly to ON1 (89.2%, 233/261) and BA9 (92%, 277/301) genotypes, respectively, although NA1 and BA10 were also present until 2015/2016. CONCLUSION: The sequence and phylogenetic analysis reflected the relatively high diversity of Portuguese RSV strains. BA9 and ON1 genotypes, which have been circulating in Portugal since 2010/2011 and 2011/2012 respectively, predominated during the whole study period.
Asunto(s)
Variación Genética , Infecciones por Virus Sincitial Respiratorio/epidemiología , Virus Sincitial Respiratorio Humano/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , ADN Viral/genética , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Filogenia , Portugal/epidemiología , Prevalencia , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/clasificación , Infecciones del Sistema Respiratorio/virología , Estaciones del Año , Vigilancia de Guardia , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
The ATP-binding cassette transporter 6 (ABCC6) gene encodes a cellular transmembrane protein transporter (MRP6) that is involved in the regulation of tissue calcification in mammals. Mutations in ABCC6 are associated with human ectopic calcification disorders. To gain insight into its evolution and involvement in tissue calcification we conducted a comparative analysis of the ABCC6 gene and the related gene ABCC1 from invertebrates to vertebrates where a bony endoskeleton first evolved. Taking into consideration the role of ABCC6 in ectopic calcification of human skin we analysed the involvement of both genes in the regeneration of scales, mineralized structures that develop in fish skin. The ABCC6 gene was only found in bony vertebrate genomes and was absent from Elasmobranchs, Agnatha and from invertebrates. In teleost fish the abcc6 gene duplicated but the two genes persisted only in some teleost genomes. Six disease causing amino acid mutations in human MRP6 are a normal feature of abcc6 in fish, suggesting they do not have a deleterious effect on the protein. After scale removal the abcc6 (5 and 10 days) and abcc1 (10 days) gene expression was up-regulated relative to the intact control skin and this coincided with a time of intense scale mineralization.
Asunto(s)
Calcificación Fisiológica , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Seudoxantoma Elástico/genética , Secuencia de Aminoácidos , Animales , Secuencia Conservada , Evolución Molecular , Humanos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/química , Mutación , Filogenia , Seudoxantoma Elástico/veterinaria , Sintenía , TranscriptomaRESUMEN
OBJECTIVES: Ankylosing spondylitis (AS) is the most prevalent form of spondyloarthritis, with a known genetic association with the HLA-B27 molecule. The aim of this study was to assess the contribution of the HLA-G, HLA-E and HLA-F to AS susceptibility/protection in Portuguese patients with HLA-B27 AS and HLA-B27 unaffected controls. METHODS: High-resolution typing of HLA-G, HLA-E and HLA-F was performed in 228 patients with HLA-B27 AS and 244 HLA-B27 unaffected controls. Allelic, genotypic and haplotypic frequencies were compared between cohorts. To replicate the results, single nucleotide polymorphisms (SNPs) in HLA-E and HLA-F genes were typed in Australian cohorts. For further confirmation, a group of European-descent patients with AS and unaffected controls were genotyped for Major Histocompatibility Complex SNPs using the Illumina microarray. RESULTS: In the Portuguese population, no significant differences were found in HLA-G. For HLA-E, a significant difference was detected for the genotype HLA-E*01:01:01/01:03:01 (p=0.009; pc=0.009; OR=0.51), with a protection effect. For HLA-F, significant differences were detected in the allele HLA-F*01:01:02 (p=0.0049; pc=0.0098; OR=0.60) and corresponding SNP rs2075682 (p=0.0004; pc=0.0008; OR=0.53), suggesting protection and in the genotype HLA-F*01:01:01/01:03:01 (p=0.011; pc=0.043; OR=2.00), suggesting a susceptibility effect. Three G-E-F haplotypes with significant differences were detected but occur in a very small number of individuals. The only significant differences detected in the replication studies were for HLA-E rs1059510 in the Australians and for HLA-F rs1736924 in the European-descent cohorts. CONCLUSION: Our results reveal suggestive AS protective and susceptibility effects from both HLA-E and HLA-F loci, however with population differences. To our knowledge, this is the first study showing association of HLA-F with AS.
RESUMEN
BACKGROUND: The association between susceptibility to multiple sclerosis (MS) and HLA-DRB1*15 has been reported in various European populations. OBJECTIVE: To investigate the relationship between MS, HLA-DRB1*15 and other DRB1 alleles in a Portuguese population and their association with clinical course of MS. METHODS: The HLA-DRB1 alleles were analyzed by PCR-SSP in 248 MS patients and 282 healthy controls. In order to relate HLA-DRB1 alleles to disease aggressiveness, patients with relapsing remitting MS and secondary progressive MS were subdivided into 3 groups: 'benign' MS patients who maintain an Extended Disability Status Scale (EDSS) score of
Asunto(s)
Alelos , Susceptibilidad a Enfermedades , Antígenos HLA-DR/genética , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/genética , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Análisis Mutacional de ADN , Evaluación de la Discapacidad , Femenino , Frecuencia de los Genes , Genotipo , Cadenas HLA-DRB1 , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Portugal/epidemiología , Probabilidad , Análisis de SupervivenciaRESUMEN
Twelve families with exuberant and early-onset calcium pyrophosphate dehydrate chondrocalcinosis (CC) and diffuse idiopathic skeletal hyperostosis (DISH), hereafter designated DISH/CC, were identified in Terceira Island, the Azores, Portugal. Ninety-two (92) individuals from these families were selected for whole-genome-wide linkage analysis. An identity-by-descent (IBD) analysis was performed in 10 individuals from 5 of the investigated pedigrees. The chromosome area with the maximal logarithm of the odds score (1.32; P=0.007) was not identified using the IBD/identity-by-state (IBS) analysis; therefore, it was not investigated further. From the IBD/IBS analysis, two candidate genes, LEMD3 and RSPO4, were identified and sequenced. Nine genetic variants were identified in the RSPO4 gene; one regulatory variant (rs146447064) was significantly more frequent in control individuals than in DISH/CC patients (P=0.03). Four variants were identified in LEMD3, and the rs201930700 variant was further investigated using segregation analysis. None of the genetic variants in RSPO4 or LEMD3 segregated within the studied families. Therefore, although a major genetic effect was shown to determine DISH/CC occurrence within these families, the specific genetic variants involved were not identified.
RESUMEN
INTRODUCTION: Immune profile for influenza viruses is highly changeable over time. Serological studies can assess the prevalence of influenza, estimate the risk of infection, highlight asymptomatic infection rate and can also provide data on vaccine coverage. The aims of the study were to evaluate pre-existing cross-protection against influenza A(H3) drift viruses and to assess influenza immunity in the Portuguese population. MATERIALS AND METHODS: We developed a cross-sectional study based on a convenience sample of 626 sera collected during June 2014, covering all age groups, both gender and all administrative health regions of Portugal. Sera antibody titers for seasonal and new A(H3) drift influenza virus were evaluated by hemagglutination inhibition assay (HI). Seroprevalence to each seasonal influenza vaccine strain virus and to the new A(H3) drift circulating strain was estimated by age group, gender and region and compared with seasonal influenza-like illness (ILI) incidence rates before and after the study period. RESULTS: Our findings suggest that seroprevalences of influenza A(H3) (39.9%; 95% CI: 36.2-43.8) and A(H1)pdm09 (29.7%; 95% CI: 26.3-33.4) antibodies were higher than for influenza B, in line with high ILI incidence rates for A(H3) followed by A(H1)pdm09, during 2013/2014 season. Low pre-existing cross-protection against new A(H3) drift viruses were observed in A(H3) seropositive individuals (46%). Both against influenza A(H1)pdm09 and A(H3) seroprotection was highest in younger than 14-years old. Protective antibodies against influenza B were highest in those older than 65years old, especially for B/Yamagata lineage, 33.3% (95% CI: 25.7-41.9). Women showed a high seroprevalence to influenza, although without statistical significance, when compared to men. A significant decreasing trend in seroprotection from north to south regions of Portugal mainland was observed. CONCLUSIONS: Our results emphasize that low seroprotection increases the risk of influenza infection in the following winter season. Seroepidemiological studies can inform policy makers on the need for vaccination and additional preventive measures.
Asunto(s)
Anticuerpos Antivirales/sangre , Protección Cruzada , Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Gripe Humana/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estudios Transversales , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Incidencia , Lactante , Recién Nacido , Gripe Humana/epidemiología , Masculino , Persona de Mediana Edad , Portugal/epidemiología , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
One hundred and thirty unrelated Azorean individuals were randomly selected to study the frequencies of high-resolution HLA alleles and haplotypes in the Azorean (Terceira) population. HLA-A, -B, -Cw, -DRB1, -DQA1 and -DQB1 high-resolution genotyping was performed by polymerase chain reaction using commercial kits. HLA-E, -F and -G alleles, were genotyped by sequence-based typing. All loci were in HWE, showing no locus-level deviations. The genotype data is available in the Allele Frequencies Net Database under the population name "Azores Terceira Island" and the identifier (AFND112579).
Asunto(s)
Frecuencia de los Genes , Antígenos HLA/genética , Alelos , Azores , Genotipo , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Antígenos HLA-DQ/genética , Cadenas alfa de HLA-DQ/genética , Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Antígenos HLA-G/genética , Antígenos de Histocompatibilidad Clase I/genética , Humanos , Portugal , Antígenos HLA-ERESUMEN
Our objective was to investigate the frequency of HFE gene mutations and to study linkage disequilibrium (LD) between HLA-Class I alleles and these mutations in the population of Terceira Island, Azores, Portugal. A total of 218 unrelated individuals were investigated. Three HFE mutations--C282Y, H63D, and S65C--were identified by restriction endonuclease digestion of polymerase chain reaction (PCR)-amplified genomic DNA. HLA-Class I alleles were typed by PCR-single-strand polymorphism. Gene frequencies and LD were estimated using Arlequin V 1.1. Six genotypes were found in the population: WT/WT (58.3%), H63D/WT (31.2%), H63D/H63D (2.3%), H63D/C282Y (0.9%), S65C/WT (4.1%), and C282Y/WT (3.2%). No cases of C282Y or S65C homozygosity were identified. HLA haplotype A3-B7 was in LD with C282Y; HLA alleles A29, B44, and HLA haplotype A29-B44 were in LD with S65C mutation. HFE gene frequencies in this population are similar to those in other European populations; HFE S65C mutation was found in LD with the alleles A29, B44, and with A29-B44 HLA haplotype.
Asunto(s)
Antígenos HLA-A/genética , Antígenos de Histocompatibilidad Clase I/genética , Desequilibrio de Ligamiento , Proteínas de la Membrana/genética , Azores , Haplotipos , Proteína de la Hemocromatosis , Humanos , Persona de Mediana Edad , Mutación PuntualRESUMEN
Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.
Asunto(s)
Aminopeptidasas/genética , Aminopeptidasas/metabolismo , Antígeno HLA-B27/genética , Fragmentos de Péptidos/metabolismo , Polimorfismo Genético/genética , Espondilitis Anquilosante/genética , Proteínas Adaptadoras de Señalización CARD/genética , Linfocitos T CD8-positivos/metabolismo , Estudios de Casos y Controles , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Susceptibilidad a Enfermedades , Estudio de Asociación del Genoma Completo , Humanos , Subunidad p40 de la Interleucina-12/genética , Proteínas de Unión a TGF-beta Latente/genética , Proteínas de la Membrana/genética , Metaanálisis como Asunto , Antígenos de Histocompatibilidad Menor , Receptores de Péptidos , Subtipo EP4 de Receptores de Prostaglandina E/genética , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Espondilitis Anquilosante/metabolismo , Población BlancaRESUMEN
A 72-year-old male was diagnosed as having ankylosing spondylitis, mainly according to radiological findings, confirmed as HLA-B27-negative. Postmortem examination of the skeleton raised doubts on the initial diagnosis, since spinal findings pointed out also to diffuse idiopathic skeletal hyperostosis. The authors discuss the differential diagnosis and enhance the postmortem findings which allowed the diagnosis of the two clinical entities in the same patient.
Asunto(s)
Hiperostosis Esquelética Difusa Idiopática/complicaciones , Espondilitis Anquilosante/complicaciones , Anciano , Condrocalcinosis/diagnóstico , Diagnóstico Diferencial , Resultado Fatal , Antígeno HLA-B27/inmunología , Humanos , Hiperostosis Esquelética Difusa Idiopática/diagnóstico , Hiperostosis Esquelética Difusa Idiopática/diagnóstico por imagen , Masculino , Radiografía , Espondilitis Anquilosante/diagnóstico por imagen , Espondilitis Anquilosante/inmunologíaRESUMEN
Leptospirosis is an emerging zoonotic disease caused by pathogenic species of the genus Leptospira. It has a broad range of clinical presentations in humans. Although progress has been made in the characterization of the host immune system factors that may affect disease progression and outcome, to date few reports have addressed the role of genetic polymorphisms in the susceptibility to leptospirosis. In this work a group of patients with a history of leptospiral infection and a control group were compared for polymorphisms in the human leukocyte antigen (HLA), in killer-cell immunoglobulin-like receptors (KIR), and in cytokine genes. Alleles in the HLA-A and -B loci were associated with susceptibility, as were the class I haplotype A*01-B*08-Cw*07 and the 8.1 ancestral haplotype (A*01-B*08-Cw*07-DRB1*03-DQB1*02). Single nucleotide polymorphisms in the interleukin (IL)-4 and IL-4Ralpha genes also had significantly higher frequencies in the patient group. No association was reported between KIR gene profile and leptospirosis. This work highlights the importance of using genetic polymorphisms to better understand the mechanisms involved in the immune response to leptospirosis.
Asunto(s)
Citocinas/genética , Antígenos HLA/genética , Leptospirosis/genética , Leptospirosis/inmunología , Polimorfismo Genético , Receptores KIR/genética , Alelos , Citocinas/inmunología , Genotipo , Antígenos HLA/inmunología , Humanos , Persona de Mediana Edad , Receptores KIR/inmunologíaRESUMEN
Crystal deposition is a very complex process ruled by numerous factors. A small but important proportion of cases of chondrocalcinosis are monogenic, and many of the genes involved have been identified. These genetic findings strongly point to control of the level of extracellular inorganic pyrophosphate as the primary mechanism for their association with either calcium pyrophosphate dihydrate or hydroxyapatite deposition. However, effects on extracellular inorganic pyrophosphate levels do not explain the mechanism of association in all of these monogenic diseases. Further, there are likely to be several as yet unidentified genes that are important in this common condition. This review highlights what genetic studies have demonstrated about the processes involved in these diverse but related disorders.
Asunto(s)
Condrocalcinosis/genética , Hiperostosis Esquelética Difusa Idiopática , Polimorfismo Genético/genética , Animales , Condrocalcinosis/fisiopatología , Modelos Animales de Enfermedad , Humanos , Hipofosfatasia/genética , Ratones , Proteínas de Transporte de Fosfato/genética , Hidrolasas Diéster Fosfóricas/genética , Pirofosfatasas/genéticaRESUMEN
OBJECTIVE: Twelve families that were multiply affected with diffuse idiopathic skeletal hyperostosis (DISH) and/or chondrocalcinosis, were identified on the island of Terceira, The Azores, potentially supporting the hypothesis that the 2 disorders share common etiopathogenic factors. The present study was undertaken to investigate this hypothesis. METHODS: One hundred three individuals from 12 unrelated families were assessed. Probands were identified from patients attending the Rheumatic Diseases Clinic, Hospital de Santo Espírito, in The Azores. Family members were assessed by rheumatologists and radiologists. Radiographs of all family members were obtained, including radiographs of the dorsolumbar spine, pelvis, knees, elbows, and wrists, and all cases were screened for known features of chondrocalcinosis. RESULTS: Ectopic calcifications were identified in 70 patients. The most frequent symptoms or findings were as follows: axial pain, elbow, knee and metacarpophalangeal (MCP) joint pain, swelling, and/or deformity, and radiographic enthesopathic changes. Elbow and MCP joint periarticular calcifications were observed in 35 and 5 patients, respectively, and chondrocalcinosis was identified in 12 patients. Fifteen patients had sacroiliac disease (ankylosis or sclerosis) on computed tomography scans. Fifty-two patients could be classified as having definite (17%), probable (26%), or possible (31%) DISH. Concomitant DISH and chondrocalcinosis was diagnosed in 12 patients. Pyrophosphate crystals were identified from knee effusions in 13 patients. The pattern of disease transmission was compatible with an autosomal-dominant monogenic disease. The mean age at which symptoms developed was 38 years. CONCLUSION: These families may represent a familial type of pyrophosphate arthropathy with a phenotype that includes peripheral and axial enthesopathic calcifications. The concurrence of DISH and chondrocalcinosis suggests a shared pathogenic mechanism in the 2 conditions.