RESUMO
Bovine tuberculosis (bTB) is caused by Mycobacterium bovis and disseminated worldwide. In Argentina, the highest prevalence occurs in dairy areas. BoLA DRB3.2 is related to the adaptive immunity in mycobacterial infections. Genetic polymorphisms of this marker have been associated with resistance or susceptibility to bovine diseases. We evaluated the association between BoLA DRB3.2 polymorphisms and bTB pathology scores in dairy and beef cattle breeds of Argentina. Most bovines exhibited visible lesions compatible with tuberculosis and, furthermore, 150 (85.7%) were also positive by bacteriology. A pathology index showed a variable degree of disease, from 3 to 76 (median pathology score = 9 (IQR: 7-15)). Thirty-five BoLA DRB3.2 alleles were identified with an associated frequency from 16% to 0.3%, distributed 73% (n = 128) in heterozygosis and 27% (n = 47) in homozygosis, with 12 BoLA DRB3.2 alleles (*0101, *1101, *1501, *0201, *2707 *1001, *1002, *1201, *14011, *0501 *0902 and *0701) representing the 74.7% of the population variability. A functional analysis grouped them in 4 out of 5 clusters (A-D), suggesting a functional overlapping. Among the 90 identified genotypes, *1101/*1101, *1101/*1501 and *0101/*0101 were the most frequent (10%, 8.9% and 8.9%, respectively). No association was detected between the pathology scores and a specific DRB3.2 allele (p > .05). Animals infected with M. bovis spoligotype SB0153 showed a significantly higher pathology score than those affected by the spoligotype SB0145 (p = .018). Furthermore, the Aberdeen Angus breed exhibited highest pathological scores (p < .0001), which were associated with disseminated lesion, thus suggesting that the host component could be important to the disease progression.
Assuntos
Genótipo , Antígenos de Histocompatibilidade Classe II/genética , Polimorfismo Genético , Tuberculose Bovina/patologia , Alelos , Animais , Argentina , Bovinos , Éxons , Feminino , Antígenos de Histocompatibilidade Classe II/metabolismo , Masculino , Nucleotídeos , Tuberculose Bovina/genéticaRESUMO
BACKGROUND: In Argentina, HIV diagnosis in adults is made using one or two enzyme immunoassay tests and a confirmatory test. These strategies may fail to identify infected individuals during early primary infection, which represents an important public health problem among groups with a high HIV incidence, such as men who have sex with men (MSM) (6.3% persons/year). The general objective of this study was to contribute to reducing HIV transmission among MSM through the identification of antibody-negative, nucleic acid-positive individuals. FINDINGS: A total of 1549 MSM were recruited for an HIV seroprevalence study. A total of 161 (10.4%) MSM were HIV-positive and 14 (0.9%) were indeterminate. Among the 1374 negative individuals, 16 (1.2%) exhibited reactive results in the screening assay. Indeterminate Western blot (WB) samples and negative WB samples (with discordant results in the screening) were analysed to detect HIV nucleic acid by viral load testing. Up to 23.1% of HIV-indeterminate WB samples and 7.1% of HIV-negative WB samples with discordant results in the screening assays had detectable nucleic acid. Overall, 14.8% of the samples with discordant or indeterminate results were identified as HIV-positive using direct diagnosis. With the identification of four new cases using the nucleic acid detection test, the HIV prevalence in MSM increased by 0.3% (from 10.4 to 10.7%). CONCLUSIONS: The results of this study suggest the importance of including nucleic acid detection in the HIV algorithm for MSM with HIV-indeterminate WB results and those with HIV-negative WB results and discordant results in screening assays, in order to decrease HIV transmission among this population with a high HIV prevalence and incidence.
Assuntos
DNA Viral/sangue , Anticorpos Anti-HIV/sangue , Soropositividade para HIV/diagnóstico , HIV-1 , Homossexualidade Masculina , Técnicas de Amplificação de Ácido Nucleico , RNA Viral/sangue , Adulto , Algoritmos , Argentina/epidemiologia , Análise Custo-Benefício , DNA Viral/genética , Diagnóstico Precoce , Soropositividade para HIV/epidemiologia , HIV-1/genética , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Incidência , Masculino , Programas de Rastreamento , Prevalência , RNA Viral/genética , Carga ViralRESUMO
An HIV incidence estimation was performed among men who have sex with men (MSM), drug users (DUs), sex workers (SWs), and pregnant women (PW) from Argentina. Volunteers older than 18 years old without a previous HIV-positive diagnosis were included. HIV-positive samples were analyzed by the Serological Testing Algorithm for Recent HIV Seroconversion (STARHS) to estimate incidence. By partial RT-PCR and sequencing of the HIV pol gene, an HIV subtype and resistance profile were determined. A total of 12,192 volunteers were recruited from October 2006 to September 2008. A higher HIV prevalence was detected among trans SWs (33.9%, 38/112), male SWs (10.8%, 12/111), and MSM 10.4% (161/1549). HIV incidence estimates by STARHS was also higher on trans SWs (11.31 per 100 person-years), male SWs (6.06 per 100 person-years), and MSM (6.36 per 100 person-years). Antiretroviral primary resistant mutations were detected in 8.4% of the study group, with a higher frequency in female DUs (33.3%). Phylogenetic analysis showed that 124 (57.9%) samples were subtype B, 84 (39.3%) intersubtype BF recombinants, 5 (2.3%) subtype C, and 1 (0.5%) subtype F in the pol region. Subtype B was most commonly found in MSM and male SWs whereas the intersubtype BF recombinant was more prevalent in female DUs, female SWs, and PW. Given the high HIV prevalence and incidence found in most of these groups, monitoring the continuing spread of the HIV epidemic is essential for determining public health priorities, assessing the impact of interventions, and estimating current and future health care needs.
Assuntos
Antirretrovirais/farmacologia , Farmacorresistência Viral , Infecções por HIV/epidemiologia , HIV-1/classificação , HIV-1/efeitos dos fármacos , Adulto , Argentina/epidemiologia , Análise por Conglomerados , Feminino , Genótipo , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Homossexualidade Masculina , Humanos , Incidência , Masculino , Filogenia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Trabalho Sexual , Transtornos Relacionados ao Uso de Substâncias/complicações , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genéticaRESUMO
The aim of this study was to evaluate the prevalence of human immunodeficiency virus (HIV)-Trypanosoma cruzi co-infection in a Buenos Aires health center. A retrospective analysis of the clinical charts of 602 HIV-infected patients was performed. Only 51.3% of the patients were evaluated against T. cruzi. The global co-infection prevalence was 4.2%, being more frequent among injectable drug users (IDU) (8.9% vs. 2.6%, < 0.05). The indication of T. cruzi testing should be stressed for HIV-infected patients, especially in those centers where IDU are assisted.
Assuntos
Doença de Chagas/complicações , Doença de Chagas/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Argentina , Feminino , Humanos , Masculino , Prevalência , Estudos RetrospectivosRESUMO
Se evaluó la prevalencia de coinfección virus de la inmunodeficiencia humana (VIH)- Trypanosoma cruzi ( T. cruzi) en pacientes atendidos en un centro asistencial de Buenos Aires, Argentina. Se realizó un análisis retrospectivo de las historias clínicas de 602 individuos VIH positivos. Sólo en el 51,3% de estos pacientes se había investigado la presencia de T. cruzi. La prevalencia global de coinfección fue del 4,2%, siendo más elevada en usuarios de drogas inyectables (UDI) (8,9% vs. 2,6%, p<0,05). Sobre la base de estos resultados, concluimos que debería enfatizarse el cumplimiento de la indicación de diagnóstico para la enfermedad de Chagas en pacientes VIH positivos, especialmente en UDI.
The aim of this study was to evaluate the prevalence of human immunodeficiency virus (HIV)- Trypanosoma cruzi co-infection in a Buenos Aires health center. A retrospective analysis of the clinical charts of 602 HIV-infected patients was performed. Only 51.3% of the patients were evaluated against T. cruzi. The global co-infection prevalence was 4.2%, being more frequent among injectable drug users (IDU) (8.9% vs. 2.6%, p<0.05). The indication of T. cruzi testing should be stressed for HIV-infected patients, especially in those centers where IDU are assisted.
Assuntos
Feminino , Humanos , Masculino , Doença de Chagas/complicações , Doença de Chagas/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Argentina , Prevalência , Estudos RetrospectivosRESUMO
HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is characterized by axonal degeneration of the corticospinal tracts. The specific requirements for transport of proteins and organelles to the distal part of the long axon are crucial in the corticospinal tracts. Microtubule dysfunction could be involved in this disease, configuring an axonal transport disease. We measured tubulin and its post-translational modified forms (acetylated and tyrosinated) in CSF of patients and controls, as well as tau and its phosphorylated forms. There were no significant differences in the contents of tubulin and acetyl-tubulin between patients and controls; tyrosyl-tubulin was not detected. In HAM/TSP, tau levels were significantly reduced, while the ratio of pT181/total tau was higher in patients than in controls, this being completely different from what is reported in other neurodegenerative diseases. Phosphorylation at T181 was also confirmed by Mass Spectrometry analysis. Western Blotting with monospecific polyclonal antibodies against pS199, pT205, pT231, pS262, pS356, pS396, pS404 and pS422 did not show differences in phosphorylation in these residues between patients and controls. Treating human SH-SY5Y neuroblastoma cells, a well-known in vitro neurite retraction model, with culture supernatant of MT-2 cells (HTLV-I infected cell line that secretes the viral Tax protein) we observed neurite retraction and an increase in tau phosphorylation at T181. A disruption of normal phosphorylation of tau protein in T181 could result in its dysfunction, contributing to axonal damage.
Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical/líquido cefalorraquidiano , Tubulina (Proteína)/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Estudos de Casos e Controles , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática , Humanos , Immunoblotting , Espectrometria de Massas , Pessoa de Meia-Idade , Neuritos/patologia , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , Valores de Referência , Fatores de TempoRESUMO
HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is characterized by axonal degeneration of the corticospinal tracts. The specific requirements for transport of proteins and organelles to the distal part of the long axon are crucial in the corticospinal tracts. Microtubule dysfunction could beinvolved in this disease, configuring an axonal transport disease. We measured tubulin and its posttranslational modified forms (acetylated and tyrosinated) in CSF of patients and controls, as well as tau and its phosphorylated forms. There were no significant differences in the contents of tubulin and acetyl-tubulinbetween patients and controls; tyrosyl-tubulin was not detected. In HAM/TSP, tau levels were significantly reduced, while the ratio of pT181/total tau was higher in patients than in controls, this being completely different from what is reported in other neurodegenerative diseases. Phosphorylation at T181 was also confirmed by Mass Spectrometry analysis. Western Blotting with monospecific polyclonal antibodies against pS199, pT205, pT231, pS262, pS356, pS396, pS404 and pS422 did not show differences in phosphorylation in these residues between patients and controls. Treating human SH-SY5Y neuroblastoma cells, a well-known in vitro neurite retraction model, with culture supernatant of MT-2 cells (HTLV-I infected cell line that secretes theviral Tax protein) we observed neurite retraction and an increase in tau phosphorylation at T181. A disruptionof normal phosphorylation of tau protein in T181 could result in its dysfunction, contributing to axonal damage.
Assuntos
Idoso , Humanos , Pessoa de Meia-Idade , Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical/líquido cefalorraquidiano , Tubulina (Proteína)/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Estudos de Casos e Controles , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática , Immunoblotting , Espectrometria de Massas , Neuritos/patologia , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , Valores de Referência , Fatores de TempoRESUMO
HIV subtypes B, F, and BF recombinants have been previously reported in South America. This report describes the presence of HIV-1 subtype C infection in the countries of Argentina, Uruguay, and Paraguay dating back to at least 1999. Surveillance for uncommon non-B/non-F subtype viruses circulating in South America has been conducted in samples obtained from nine countries. Peripheral blood mononuclear cells (PBMC), dried filter paper (FP), and fresh blood (FB) samples were collected from HIV-positive patients from Ecuador, Colombia, Venezuela, Peru, Chile, Bolivia, Argentina, Uruguay, and Paraguay. From a total of 2962 HIV seropositive samples examined during a 9-year period (1995-2003), only 11 (0.4%) were found to be infected with non-B/non-F HIV variants. Eight of these 11 strains were determined to be subtype C by heteroduplex mobility assay (HMA). Five of these 8 strains were further characterized by sequencing and phylogenetic analysis of the protease (Pro) and reverse transcriptase (RT) region of the genome and two were sequenced full length. One of the strains was found to be a unique BC recombinant. The spread of a third subtype of HIV, subtype C, should raise the question of its potential future role in the HIV epidemic in this region.
Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Adulto , Argentina/epidemiologia , Feminino , Protease de HIV/genética , Transcriptase Reversa do HIV/genética , Análise Heteroduplex , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Paraguai/epidemiologia , Filogenia , Análise de Sequência de DNA , Uruguai/epidemiologiaRESUMO
The molecular epidemiology of HIV-1 in Argentina is more complex than was previously appreciated. One circulating recombinant form, CRF12_BF, and many related BF recombinant forms predominate in the capital city, Buenos Aires. This study of HIV-1 subtypes acquired perinatally between 1984 and 2000 has permitted, for the first time, a reconstruction of the history of BF recombination in Argentina. Sequencing of a partial genome region from the beginning of vpu to the beginning of env(gp120), which spans a breakpoint common in most contemporary Argentine BF recombinants, enabled samples to be rapidly screened. Among 23 children born between 1984 and 2000, 15 including 1 child born in 1986, harbored a BF recombinant. Thirteen of the 15 recombinants shared a common breakpoint at the 5' end of env(gp120). Full genome sequencing of two viruses, from 1986 and 1987, respectively, revealed them to be genetically related but not identical to CRF12_BF. Both contained more subtype B sequence than did CRF12_BF. BF recombinants related to CRF12_BF have been in circulation in Buenos Aires since 1986 and continue to predominate in perinatal transmissions.
Assuntos
Infecções por HIV/transmissão , HIV-1/genética , Transmissão Vertical de Doenças Infecciosas , Adolescente , Argentina/epidemiologia , Criança , Pré-Escolar , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/epidemiologia , Protease de HIV/genética , Transcriptase Reversa do HIV/genética , HIV-1/classificação , Proteínas do Vírus da Imunodeficiência Humana , Humanos , Lactente , Filogenia , RNA/genética , RNA Viral/genética , Análise de Sequência , Proteínas Virais Reguladoras e Acessórias/genéticaRESUMO
OBJECTIVE: To describe the genetic diversity of HIV-1 in South America by full genome sequencing and analysis. METHODS: Purified peripheral blood mononuclear cell DNA from HIV-infected individuals in Argentina, Uruguay and Bolivia was used to amplify full HIV-1 genomes. These were sequenced using the ABI 3100 automated sequencer and phylogenetically analysed. RESULTS: Twenty-one HIV-1 strains from three South American countries, 17 of which were pre-screened by envelope heteroduplex mobility assay (HMA), were studied. Ten out of 10 HMA subtype F and four out of seven HMA subtype B strains were actually BF recombinants upon full genome analysis. Two BF recombinants from Argentina and two from Uruguay had the same structure, representing a new circulating recombinant form termed CRF12_BF(ARMA159). Twelve other BF recombinants had structures related to CRF12 but with additional segments of subtype B; each was unique. BF recombinants were temporally and geographically widespread, found as early as 1986-1987 in vertically infected Argentinian children and in Argentina, Uruguay, and Bolivia.
Assuntos
Infecções por HIV/epidemiologia , HIV-1/classificação , HIV-1/genética , Recombinação Genética , Adulto , Feminino , Infecções por HIV/virologia , Análise Heteroduplex , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNA , América do Sul/epidemiologiaRESUMO
Detection of anti-HIV-1 IgA antibodies using a modified ELISA test for the early diagnosis of perinatally acquired HIV-1 infection in children treated with protocol ACTG 076 was evaluated. A total of 177 sera were obtained from 141 infants between 1 and 12 months of age (46 were treated and 95 were non-treated with protocol ACTG 076) and tested for HIV IgA antibodies by an ELISA test after removal of IgG with recombinant protein G. Infants were classified according to CDC's classification system after a follow-up until 20 months of age. Of the 46 treated children 22 turned out to be infected and in the group of 95 untreated children, 52 were infected. All 81 samples from uninfected children treated or untreated with protocol ACTG 076 were persistently IgA-negative. HIV IgA antibodies were detected in 14 of 25 plasma samples from infected children with treatment, and in 58 of 71 samples in infected children without treatment. Considering that the sensitivity of this test is lower in children younger than 6 months the population of children studied was divided into two groups; those under and those over 6 months of age. No significant differences were observed in the detection of IgA in treated or untreated children in both age groups. The overall specificity of the test was 100 per cent; sensitivity in children older than 6 months was 76.92 per cent in treated children and 93.10 per cent in untreated children. In spite of the small number of samples studied it could be demonstrated that treatment with zidovudine does not affect the detection of IgA antibodies. This is a simple and inexpensive method that could be used for diagnosis of treated and untreated children in developing countries.
Assuntos
Anticorpos Antivirais/isolamento & purificação , Infecções por HIV/transmissão , HIV-1 , Imunoglobulina A/imunologia , Transmissão Vertical de Doenças Infecciosas , Antivirais/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Lactente , Reprodutibilidade dos Testes , Zidovudina/uso terapêuticoRESUMO
Soon after HIV (Human Immunodeficiency Virus) was discovered, its characteristics level of diversity and variability was established. So far, within HIV-1 it is known that there exist 3 main groups, 9 subtypes and at least 12 recombinant forms. Not only does this diversity affect taxonomy, but also prophylaxis and therapy for HIV infection. Numerous studies worldwide have demonstrated the influence this variability has on both diagnosis and monitoring assays as well as on the pathogenesis of HIV infection. In Argentina, from the molecular point of view, the epidemic shows a complex pattern. HIV-1 subtypes B and F have been described as well as a recombinant B/F form. Epidemiology and molecular data suggest high percentage levels and a great diversity of these recombinant forms in the heterosexual population.
Assuntos
Variação Genética , HIV/genética , Recombinação Genética , Argentina , HIV/classificação , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , HumanosRESUMO
Soon after HIV (Human Immunodeficiency Virus) was discovered, its characteristics level of diversity and variability was established. So far, within HIV-1 it is known that there exist 3 main groups, 9 subtypes and at least 12 recombinant forms. Not only does this diversity affect taxonomy, but also prophylaxis and therapy for HIV infection. Numerous studies worldwide have demonstrated the influence this variability has on both diagnosis and monitoring assays as well as on the pathogenesis of HIV infection. In Argentina, from the molecular point of view, the epidemic shows a complex pattern. HIV-1 subtypes B and F have been described as well as a recombinant B/F form. Epidemiology and molecular data suggest high percentage levels and a great diversity of these recombinant forms in the heterosexual population.
RESUMO
PROBLEM: Alloimmunization as a treatment for recurrent spontaneous abortion (RSA) is still controversial due to the lack of enough controls to evaluate its effectiveness. The present study was conducted to compare the live birth rate in the presence or absence of immunotherapy. METHOD OF STUDY: Ninety-two women with RSA (79 primary [PA] and 13 secondary aborters[SA]) received immunotherapy. Thirty-seven RSA couples not receiving paternal alloimmunization, constituted the "control" group. RESULTS: The pregnancy rate in alloimmunized was 58 vs 46% in the control group. The live birth increased from 71% in the controls to 88% after immunotherapy. The alloimmunization induced mixed lymphocyte reaction blocking factors (MLR BFs) in 79% of women. However, they were also present in 83% of immunized women experiencing a new abortion. CONCLUSION: These results indicate that alloimmunization may be useful in the treatment of RSA.
Assuntos
Aborto Habitual/terapia , Pai , Leucócitos Mononucleares/imunologia , Vacinação , Aborto Habitual/etiologia , Adulto , Feminino , Frequência do Gene , Antígenos HLA-DQ/genética , Cadeias beta de HLA-DQ , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Humanos , Imunoterapia/métodos , Masculino , GravidezRESUMO
The aim of this study was to compare major histocompatibility complex (MHC) class II susceptibility to type 1 autoimmune hepatitis (AH) between children and adults of the same ethnic group. HLA-DRB1, HLA-DRB3, HLA-DQA1, and HLA-DQB1 gene subtypes were examined by high resolution oligonucleotide typing in 122 pediatric (PAH) and 84 adult (AAH) patients and in 208 controls. In children, HLA-DRB1*1301 was the primary susceptibility allele (66.4% patients vs. 10.6% controls, relative risk [RR] = 16.3, Pc < 10(-24)) whereas HLA-DRB1*1302, which differs from HLA-DRB1*1301 by only 1 amino acid, appeared to be protective. The exclusion of individuals with HLA-DRB1*1301 from control and pediatric patients allowed us to find a secondary association of PAH with HLA-DRB1*0301. Possession of HLA-DRB1*1301, however, was associated with a lower therapeutic response rate. Analysis of peptide binding pocket residues indicated that Tyr 10, Ser 11, Ser 13, and Val 86 in the class II beta chain were present in 85% of patients compared with 37% of controls, suggesting that a high proportion of AH susceptibility is attributable to these residues (etiologic fraction [EF] = 76%). In contrast to the class II associations in children, AAH was associated with HLA-DRB1*0405 (RR = 10.4, Pc <.005) but not with HLA-DRB1*1301 or HLA-DRB1*0301. In addition, HLA-DR4 with the class I gene, HLA-A11, appeared synergistic in predisposing AAH patients to develop extra-hepatic autoimmune (AI) manifestations (odds ratio [OR] = 104.9, Pc < 10(-4)). Concomitant differences in autoantibody profiles were also observed in PAH versus AAH: smooth muscle antibodies (SMA) were most prevalent in PAH but antinuclear antibodies were most prevalent in AAH (P =.003). This study therefore reveals that different HLA-DRB1 allotypes confer susceptibility to AH in children and adults and raises the possibility that PAH and AAH may be triggered by different factors.
Assuntos
Genes MHC da Classe II , Predisposição Genética para Doença/genética , Hepatite Autoimune/genética , Hepatite Autoimune/imunologia , Adulto , Idade de Início , Alelos , Motivos de Aminoácidos , Argentina , Autoanticorpos/imunologia , Criança , Etnicidade/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DQ/imunologia , Antígenos HLA-DR/química , Antígenos HLA-DR/genética , Antígenos HLA-DR/imunologia , Haplótipos , Hepatite Autoimune/fisiopatologia , Hepatite Autoimune/terapia , Humanos , Desequilíbrio de Ligação/genética , Recidiva , Taxa de Sobrevida , Resultado do TratamentoRESUMO
The association of HLA antigens and type I or "lupoid" CAH-C was investigated in a population of 52 Argentinian Caucasoid patients. When compared with a population of normal individuals of the same ethnic group (n = 197), a significant increase of HLA-DR6 was observed (68.6% in patients vs 17.3% in controls; RR = 12.3, chi 2 = 52.4, pc = 0.00001). DNA typing showed that the HLA-DRB1*1301 allele was present in 32 out of 33 HLA-DR6 patients (66.6% of all the C-CAH patients vs 10.5% in controls; RR = 16.2, chi 2 = 111.3, pc = 0.00001). Analysis of HLA-DQB1 alleles also showed a significant increase of DQB1*0603 (RR = 15.4, chi 2 = 106.5, pc = 0.00001), an allele found in strong linkage disequilibrium with DRB1*1301. The association of CAH-C with this particular HLA-DR6 haplotype has not been previously described for the adult onset CAH. This different HLA predisposition, together with the fact that extrahepatic autoimmune diseases occur frequently only in the adult form of the disease, suggest that the immunopathogenic mechanisms involved in the development of these diseases may be different.
Assuntos
Doenças Autoimunes/genética , Antígenos HLA-DR/genética , Haplótipos/genética , Hepatite Crônica/genética , Adolescente , Doenças Autoimunes/imunologia , Criança , Pré-Escolar , DNA/análise , Feminino , Antígeno HLA-DR6/genética , Cadeias HLA-DRB1 , Hepatite Crônica/imunologia , Humanos , MasculinoRESUMO
We investigated the association of human leukocyte antigen antigens and type 1 chronic active "autoimmune" hepatitis in a population of 65 white Argentinian patients, taking into account the different manifestations of the disease. Standard microlymphocytotoxicity was used for human leukocyte antigen A, B, C, DR and DQ typing. Human leukocyte antigen class 2 alleles were also typed on genomic DNA by means of polymerase chain reaction amplification and hybridization to sequence specific oligonucleotides. A primary association with human leukocyte antigen DR4 was present (human leukocyte antigen DR4: 44% in patients vs. 29% in controls; chi 2, 5.6; p = 0.02, relative risk, 2.1). However, a novel association was observed with human leukocyte antigen A11 (31% in patients vs. 6% in the controls; chi 2, 25.3; corrected p = 0.001; relative risk, 6.8). Moreover, of the 20 human leukocyte antigen A11 patients, 18 had extrahepatic manifestations associated with autoimmune chronic active hepatitis. This represented 60% of the patients bearing this form of the disease (n = 30), conferring a relative risk of 22.2 (chi 2, 46.3; corrected p = 0.00008). In this group, human leukocyte antigen DR3 and DR4 had a weak association. When present together, human leukocyte antigen DR4 and human leukocyte antigen A11 had a synergistic effect, yielding an odds ratio of 357. Statistical analysis and family segregation studies suggest that the two loci products may represent independent risk factors for this form of autoimmune chronic active hepatitis. This synergistic effect was not evident with A11 plus DR3. In autoimmune chronic active hepatitis patients without extrahepatic manifestations, a weak association with human leukocyte antigen DR6 was found.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Doenças Autoimunes/imunologia , Antígenos HLA/sangue , Hepatite Crônica/imunologia , Adolescente , Adulto , Idoso , Alelos , Argentina/epidemiologia , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/genética , Distribuição de Qui-Quadrado , Feminino , Seguimentos , Frequência do Gene , Predisposição Genética para Doença , Antígenos HLA/classificação , Antígenos HLA/genética , Hepatite Crônica/epidemiologia , Hepatite Crônica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de RiscoRESUMO
Human minor histocompatibility antigen-specific, HLA-B*3501-restricted cytotoxic T-cell clones were assayed on a panel of 25 different target cells previously typed by serology as HLA-B35. Cells from 6 donors were not killed and cells from 2 of these were further studied by molecular cloning to characterize their HLA class I alleles. Two new HLA-B35 subtypes were identified. The sequence of one of them differs from B*3501 by one nucleotide change at codon 156, replacing a Leu for an Arg. The sequence of the other new subtype also shows a single nucleotide change compared to B*3501, with Gly-->Val substitution at residue 16. With these new variants, the allelic complexity of HLA-B35 extends now to eight subtypes.