RESUMO
This study explores the effect of priming rhesus monkeys with an Ad5/35 vector expressing simian immunodeficiency virus (SIV) gag and gp120, and then boosting the animals with an modified vaccinia virus Ankara (MVA) vector encoding the same antigens after a 2-month interval. The animals were intravenously challenged with 100 TCID50 of highly pathogenic SIVmac239 virus 2 months after the booster vaccination. The priming vaccination induced robust SIV-specific cell-mediated and humoral immune responses, and boosting further enhanced the cellular immunity. Vaccination reduced peak and long-term viral loads by 1-2 logs for a period of >6 months, as reflected by a reduction in both the SIV RNA and DNA levels. Of considerable interest, the immunized monkeys did not suffer from loss of CD4 T cells, particularly central memory CD4 T cells. These results demonstrate that prophylactic vaccination with Ad5/35 followed by MVA reduces viral replication and prevents CD4 T-cell loss, and that these effects may decrease the likelihood of disease progression.
Assuntos
Adenoviridae/genética , Vetores Genéticos , Imunização Secundária , Vacinas contra a SAIDS/uso terapêutico , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vaccinia virus/genética , Animais , Genes gag , Imunidade Celular , Imunidade Humoral , Esquemas de Imunização , Macaca mulatta , Glicoproteínas de Membrana/genética , Vacinas contra a SAIDS/imunologia , Linfócitos T/imunologia , Proteínas do Envelope Viral/genética , Carga ViralRESUMO
Behçet's disease (BD) is a chronic inflammatory disease characterized by oral aphthous ulcers, genital ulcers, uveitis and skin lesions. Etiology and pathogenesis of BD are not fully elucidated, but the association with human leukocyte antigen (HLA)-B51 or B*5101 has been repeatedly reported. Previous studies have shown that there are few sequence variations in the protein-coding region of B51, while there is a report on many variations in the 5'-flanking region and intron. In this study, HLA-B*5101 gene from 37 individuals including Japanese, Turkish, Jordanian and Iranian patients and healthy controls were fully sequenced to further clarify the B*5101 gene in association with BD. We found that all the patients and healthy controls carried B*510101 with no variation in the 5'-flanking region, exon and intron. However, seven polymorphisms were found in the 3'-flanking region. These polymorphisms composed of six haplotypes that were shared and stretched over the ethnic groups, suggesting that the susceptibility to BD was conferred by the B*510101 itself and not by any genes in linkage disequilibrium with B*510101. In addition, phylogenetic analyses of B*510101 showed that the 3'-flanking sequences followed an evolutional divergence differently from that of the other regions, implying that a unifying selection might operate to conserve B*510101.
Assuntos
Síndrome de Behçet/genética , Antígenos HLA-B/genética , Haplótipos/genética , Sequência de Bases , Éxons , Predisposição Genética para Doença , Antígeno HLA-B51 , Humanos , Íntrons , Dados de Sequência Molecular , Filogenia , Polimorfismo GenéticoRESUMO
OBJECTIVE: To evaluate the activation status of circulating CD4+, CD8+, and gammadelta T cells in patients with active and inactive Behçet's disease (BD). METHODS: We studied 11 subjects with active BD, 28 with inactive BD, and 13 healthy controls. The expression of CD4, CD8, pan-gammadelta, Vdelta1, and Vdelta2 along with the early activation marker CD69 was analyzed by 3-color flow cytometry. RESULTS: Proportions of activated CD8+ and gammadelta T cells were significantly greater in patients with active BD than in those with inactive BD or healthy control subjects, but the proportion of activated CD4+ T cells did not differ among these 3 groups. In addition, significantly greater proportions of the Vdelta1+ and Vdelta2+ gammadelta T-cell subsets were activated in patients with active BD than in those with inactive BD or healthy controls; in active BD, the balance of activation between these subsets favored the Vdelta1+ T cells. No significant differences in these proportions were found between subjects with inactive BD and healthy controls. These findings were observed exclusively in patients with HLA-B51. A comparison of samples from 5 patients taken during active BD and after resolution of BD-related symptoms showed the proportions of activated CD8+ and gammadelta T cells dropped when the patients' BD became inactive. CONCLUSION: CD8+ and gammadelta T cells, rather than CD4+ T cells, were activated in vivo in patients with active BD and HLA-B51, but not in those with inactive BD, suggesting that these potentially cytotoxic T cells play a critical role in BD flares.
Assuntos
Síndrome de Behçet/imunologia , Linfócitos T CD8-Positivos/imunologia , Antígenos HLA-B/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Linfócitos T CD4-Positivos/imunologia , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Antígeno HLA-B51 , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-IdadeRESUMO
This paper describes a case of vertical distraction osteogenesis of a free vascularized osteocutaneous scapular flap in the reconstructed mandible before implant therapy. The patient was a 67-year-old woman with squamous cell carcinoma of the right lower gingiva. She underwent segmental mandibulectomy for tumor ablation and reconstruction with an osteocutaneous scapular flap. The distraction protocol, clinical course and implant therapy are presented. Through this procedure, the bone height of the scapular graft increased by 10mm. Implants with adequate length could be placed in the distracted area. Two years after masticatory loading, the condition of these implants was stable. Vertical distraction osteogenesis of the scapular flap was considered effective when performed before implant therapy, to facilitate postoperative functional and esthetic restoration after tumor resection.
Assuntos
Aumento do Rebordo Alveolar/métodos , Mandíbula/cirurgia , Osteogênese por Distração , Retalhos Cirúrgicos , Idoso , Transplante Ósseo , Carcinoma de Células Escamosas/cirurgia , Implantação Dentária Endóssea , Feminino , Neoplasias Gengivais/cirurgia , Humanos , Procedimentos de Cirurgia Plástica , Escápula/transplante , Transplante de Pele , Retalhos Cirúrgicos/irrigação sanguínea , Dimensão VerticalRESUMO
PURPOSE: To report a spontaneous closure of a macular hole (MH) that was caused by a ruptured retinal arterial macroaneurysm (RAM). METHODS: Observational case report. Clinical examinations and optical coherence tomographic (OCT) evaluations of the retina of a 73-year-old woman who developed a MH secondary to a ruptured RAM. RESULTS: The first sign of a closure of the MH was the appearance of tissue bridging the MH in the OCT images. Later, OCT images showed a hyperreflective tissue, probably glial cells, that connected the bridging tissue to the RPE. Seven months after the first examination, the hyperreflective tissue was smaller and the shape of the foveal pit had recovered. CONCLUSIONS: A spontaneous closure of a MH caused by a ruptured RAM can occur and surgical intervention was not necessary. The tissue bridging over the MH and the hyperreflective tissue connecting the bridging tissue to the RPE most likely were involved in the spontaneous MH closure.
Assuntos
Aneurisma Roto/complicações , Artéria Retiniana/patologia , Perfurações Retinianas/etiologia , Perfurações Retinianas/fisiopatologia , Idoso , Aneurisma Roto/diagnóstico , Feminino , Angiofluoresceinografia , Humanos , Remissão Espontânea , Perfurações Retinianas/diagnóstico , Tomografia de Coerência ÓpticaRESUMO
PURPOSE: To evaluate anterior chamber biometry of the eyes of normal children using ultrasound biomicroscopy (UBM) and to evaluate the differences in biometry between children and adults, and before and after pupil dilation in children. METHODS: Anterior chamber depth (ACD) and trabecular-iris angle (TIA) were measured in 94 normal children and 15 normal adults using UBM. Before and after pupil dilation were measured in 42 children with emmetropic and hyperopic eyes. RESULTS: In 66 emmetropic children, ACD and TIA were 2.93+/-0.18 mm and 34.42+/-4.02 degrees, respectively. In 28 hyperopic children, ACD and TIA were 2.92+/-0.21 mm and 35.05+/-4.42 degrees, respectively. There was no significant difference in anterior chamber biometry associated with the refraction. ACD did not differ between children and adults, but TIA in children was wider than in adults. There was no significant difference in ACD or TIA before versus after pupil dilation in any case. CONCLUSIONS: Anterior chamber biometry in children showed no differences before and after pupil dilation. Also, there was no difference in ACD of children as compared to adults; however, TIA in children was significantly wider than in adults.
Assuntos
Câmara Anterior/diagnóstico por imagem , Iris/diagnóstico por imagem , Microscopia Acústica , Pupila/efeitos dos fármacos , Malha Trabecular/diagnóstico por imagem , Adolescente , Adulto , Biometria , Criança , Pré-Escolar , Humanos , Lactente , Pessoa de Meia-Idade , Midriáticos/administração & dosagem , Tropicamida/administração & dosagemRESUMO
We have induced suppressor T cells (Ts), capable of delaying allogeneic skin graft rejection, through the intravenous administration of allogeneic spleen cells under normal conditions. H-2 and non-H-2 incompatibility between recipient mice and donor skins induced strong graft rejection. However, when the Ts were transferred into recipient mice, the mean survival time was prolonged for every combination between recipient mice and donor skin. Studies using several strains of congenic mice revealed the antigen specificity of these Ts. Treatment with monoclonal anti-Lyt-2.2 or anti-Thy-1.2 antibody and complement abolished the suppression shown by the Ts of skin graft rejection. The suppression induced by these Ts, however, was resistant to treatment with monoclonal anti-Lyt-1.2, anti-L3T4, or anti-I-A antibody and complement. These results showed that the Ts were Lyt-1-2+, L3T4-, Ia-, T cells.
Assuntos
Tolerância Imunológica , Transplante de Pele , Linfócitos T Reguladores/imunologia , Linfócitos T/imunologia , Animais , Anticorpos Monoclonais , Epitopos/imunologia , Feminino , Sobrevivência de Enxerto , Isoantígenos/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BLRESUMO
Ninety Japanese patients with Behçet's disease (BD) were typed for human leukocyte antigen (HLA)-DRB1, -DQA1-, -DQB1, and -DPB1 alleles by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and for HLA-A, -B, -C, -DR, and -DQ antigens by conventional serologic typing. Serologic HLA typing showed a remarkably significant increase of HLA-B51 and a significant decrease of HLA-DQw1 in the patients with BD, especially those with ocular lesions including complete type, as compared with the control group (for B51, chi-squared = 46.75, P corrected < 0.001, relative risk [RR] = 7.9; for DQw1, chi-squared = 12.10, P corrected < 0.01, RR = 0.4). By PCR-RFLP genotyping, no significant difference was revealed in any class II alleles between the patient and the control groups in the corrected P value test, but P value analysis showed the significantly high frequency of DRB1*0802 and the significantly low frequencies of DQA1*0103, DQB1*0601, and DQB1*0501. No significant difference was observed in any DPB1 alleles by either P value analysis. These results indicated that the primary and primordial gene(s) responsible for the susceptibility to BD, especially related to ocular lesions, were not located in the HLA class II gene region but were in or very close to the HLA-B locus in the class I region. They also suggested the possibility that BD was a symptom complex associated with some independent diseases.
Assuntos
Síndrome de Behçet/genética , DNA/análise , Antígenos HLA/análise , Antígenos HLA-B/análise , Alelos , Síndrome de Behçet/imunologia , Genótipo , Antígenos HLA/genética , Antígeno HLA-B51 , Humanos , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
Behçet's disease is known to be associated with HLA-B51. To address the possibility that a non-human leukocyte antigen (HLA) gene closely linked to the HLA-B gene, such as tumor necrosis factor (TNF)-alpha, TNF-beta, or ECl (the locus that determines the susceptibility to alloreactive natural killer [NK] cells), is involved in the susceptibility to Behçet's disease, NcoI and EcoRI restriction fragment length polymorphisms in the TNF-beta gene and the susceptibility to lysis by alloreactive NK cells were investigated in Behçet's patients. In our NcoI restriction fragment length polymorphism (RFLP) analysis in the TNF-beta gene, the frequency of the NcoI 5.5 kb homozygote was decreased considerably in the patients, especially those with the ocular lesions, in relation to the healthy controls. However, no significant difference was observed between these groups in the EcoRI RFLP band distribution in this gene or the in susceptibility to lysis by alloreactive NK cells. These results indicated that a non-HLA gene located around the TNF gene region centromic of the HLA-B gene was a candidate to control the genetic susceptibility to Behçet's disease.
Assuntos
Síndrome de Behçet/genética , Síndrome de Behçet/imunologia , Células Matadoras Naturais/imunologia , Linfotoxina-alfa/genética , Sequência de Bases , Southern Blotting , Citotoxicidade Imunológica/imunologia , DNA/análise , Frequência do Gene , Predisposição Genética para Doença , Antígenos HLA-B/genética , Humanos , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de RestriçãoRESUMO
PURPOSE: HLA-B27-associated acute anterior uveitis (HLA-B27 AAU) seems to be triggered by external factors in persons with a particular genetic background. It is still uncertain whether HLA-B27 or other gene(s) near the HLA-B region predisposes to uveitis in a linkage disequilibrium with B27. The authors investigated microsatellite polymorphism within the transmembrane region of the MICA gene, located 47 kb centromeric of the HLA-B gene, and HLA-B27 subtypes. METHODS: Seventeen HLA-B27-positive Japanese patients with HLA-B27 AAU, 51 Japanese controls, and 20 B27-positive Japanese controls were examined for MICA gene polymorphism within the transmembrane region using polymerase chain reaction (PCR) and subsequent automated fragment detection by fluorescent-based technology. Furthermore, B27-positive patients with HLA-B27 AAU and B27-positive controls were examined for HLA-B27 subtypes by the PCR-sequence-specific primer method. RESULTS: The microsatellite allele in the MICA gene, consisting of four repetitions of GCT/AGC (designated A4 allele), was present at a significantly higher phenotype frequency in the patient group (64.7%) than in the control group (25.5%) (chi 2 = 6.95, Pc = 0.042). Furthermore, the frequency of the A4 allele was significantly higher, even when compared with 20% in the B27-positive control group (chi 2 = 5.88, Pc = 0.042). The frequency of HLA-B27 subtypes was not significantly different between B27-positive patients with HLA-B27 AAU and B27-positive controls. CONCLUSIONS: These results suggest that the MICA gene itself, or other nearby gene(s), linked to the MICA A4 allele may be involved in the development of HLA-B27 AAU and that HLA-B27 subtypes are not important in the development of HLA-B27 AAU in a Japanese population.
Assuntos
Antígeno HLA-B27/genética , Antígenos de Histocompatibilidade Classe I/genética , Polimorfismo Genético , Uveíte Anterior/genética , Doença Aguda , Adulto , Alelos , Primers do DNA/química , DNA Satélite/análise , Eletroforese em Gel de Ágar , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Reação em Cadeia da PolimeraseRESUMO
PURPOSE: Behçet's disease (BD) is known to be associated with HLA-B51 in many ethnic groups. However, the pathogenic gene responsible for BD is as yet unknown. To localize the critical region of the pathogenic gene, microsatellite markers distributed around the HLA-B gene were investigated. The BD patients studied were of three ethnic origins: Japanese, Greek, or Italian. METHODS: The total group consisted of 172 BD patients, of whom were 95 Japanese, 55 Greek, and 22 Italian. Eight polymorphic microsatellite markers distributed within 1100 kb of the HLA-B gene were analyzed using PCR and subsequent automated fragment detection by fluorescent-based technology. RESULTS: Among the eight markers, allele 348 of the MIB microsatellite was remarkably common in all three BD populations (Japanese, PC: = 0.000014; Greek, PC: = 0. 00047; Italian, PC: = 0.11). However, HLA-B51 was found to be the marker most strongly associated with BD in each population (Japanese, PC: = 0.000000000017; Greek, PC: = 0.00000032; Italian, PC: = 0. 0074). In genotypic differentiation between the patients and controls, only HLA-B51 was found to be significantly associated with BD in all three populations. Stratification analysis suggested that significant associations of BD with MICA and other microsatellites resulted from a linkage disequilibrium with HLA-B51. CONCLUSIONS: These results suggest that the pathogenic gene of BD is HLA-B51 itself and not other genes located in the vicinity of HLA-B.
Assuntos
Síndrome de Behçet/genética , Genes MHC Classe I , Antígenos HLA-B/genética , Repetições de Microssatélites/genética , Síndrome de Behçet/etnologia , Mapeamento Cromossômico , DNA/análise , Eletroforese em Gel de Poliacrilamida , Frequência do Gene , Grécia/epidemiologia , Antígeno HLA-B51 , Teste de Histocompatibilidade , Humanos , Itália/epidemiologia , Japão/epidemiologia , Fenótipo , Reação em Cadeia da Polimerase , Polimorfismo GenéticoRESUMO
PURPOSE: Behçet's disease (BD) is known to be associated with HLA-B51 in many different ethnic groups. Recently MICA, a member of a novel family of the human major histocompatibility complex (MHC) class I genes termed MIC (MHC class I chain-related genes), was identified near the HLA-B gene, and a triplet repeat microsatellite polymorphism was found in the transmembrane (TM) region. Because a strong association with BD of one particular MICA-TM allele, A6, was shown in a Japanese population, the present study was conducted to investigate microsatellite polymorphism in Greek patients with BD to know whether this association is generally observed in BD occurring in other populations. METHODS: Thirty-eight Greek patients with BD and 40 ethnically matched control subjects were examined for MICA microsatellite polymorphism using polymerase chain reaction (PCR) and subsequent automated fragment detection by fluorescent-based technology. RESULTS: Similar to the Japanese patients with BD, the phenotype frequency of the MICA-TM A6 allele was significantly increased in the Greek patients with BD (50.0% in control subjects versus 86.8% in BD cases), with an odds ratio (OR) of 6.60 (P = 0.0012). The MICA-A6 allele was found in a high frequency both in males and females (weighted OR = 6.68; P = 0.0017). No association was found between the A6 allele and several disease features. A strong association exists between the MICA-TM A6 allele and the B*5101 allele in both the control subjects and patients with BD (weighted OR = 44.39; P = 0.0000023). CONCLUSIONS: This study revealed in Greek patients a strong association of BD with a particular MICA-TM allele, MICA-A6, providing insight into the molecular mechanism underlying the development of BD.
Assuntos
Síndrome de Behçet/genética , Proteínas do Olho/genética , Antígenos HLA-B/genética , Antígenos de Histocompatibilidade Classe I/genética , Proteínas de Membrana/genética , Adulto , Idoso , Alelos , Síndrome de Behçet/etnologia , Feminino , Grécia/etnologia , Antígeno HLA-B51 , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético , Repetições de Trinucleotídeos/genéticaRESUMO
Behçet's disease has been known to be strongly associated with a particular HLA-B allele, B51. To address the possibility that the HLA-C gene, which is closely linked to HLA-B but has been poorly defined for allo-antigen specificity by the serologic method is involved in the susceptibility to Behçet's disease, HLA-C genotyping was performed for 90 Japanese Behçet's disease patients by the PCR-SSP method. The frequencies of HLA-Cw*14 and -Cw*15 were significantly higher in the patient with Behçet's disease as compared to the controls (48.9% vs. 24.0%, p = 0.0005, and 17.8% vs. 7.3%, p = 0.0434, respectively). On the other hand, the frequencies of HLA-Cw*0304 and -Cw*01 were significantly decreased in the patient group as compared to the control group (7.8% vs. 25.0%, p = 0.0027, and 23.3% vs. 37.5%, p = 0.0398, respectively). The significantly higher HLA-Cw*14 and -Cw*15 alleles may tightly correlate with the B51 antigen, and hence may have increased as a result of a linkage disequilibrium with B51. Accordingly, the HLA-C allele frequencies were compared for the B51-positive or -negative patients and controls, but there was no HLA-C allele showing a significant difference between these patient and control groups. Conversely, analysis of the HLA-B allelic distribution in association with HLA-Cw*14 revealed that in the healthy controls, B44 and B51 were present at the frequencies of 57.1% and 35.7% of the HLC-Cw*14-positive individuals, respectively. In contrast, in the Cw*14-positive patients the frequency of B44 was merely 14.0% (p = 0.0001) and that of B51 was significantly high, amounting to 82.0% (p = 0.0001). These facts suggest that the pathogenic gene of Behçet's disease is not the HLA-C gene (HLA-Cw*14 and/or HLA-Cw*15) but the HLA-B gene (HLA-B51) itself or a non-HLA gene residing in the centromeric side of the HLA-B gene rather than in the telomeric side around the HLA-C gene. This finding supports our previous mapping result, which located the susceptible gene between the TNF and HLA-B genes.
Assuntos
Síndrome de Behçet/genética , Antígenos HLA-C/genética , Alelos , Sequência de Bases/genética , Genótipo , Antígenos HLA-B/genética , Humanos , Japão/epidemiologiaRESUMO
To clarify the molecular relationship between HLA loci and ulcerative colitis (UC) in Japanese patients, we performed HLA-DP genotyping by the PCR-RFLP method and studied tumor necrosis factor beta-chain genetic polymorphism by Southern hybridization, in addition to conventional serologic typing. Significant increase was observed in Bw52, DPw9 (DPB1*0901), and DR2 (DRB1*1502) in Japanese patients with UC. Linkage analysis indicated that A24-Bw52-DR2-DPw9 alleles constitute a common haplotype in Japanese UC patients. Among the patients not carrying Bw52, B13 was significantly increased and B44 was relatively increased. These Bw52, B13, and B44 alleles share the unique amino acids, serine and aspartic acid at positions 67 and 77, respectively. These positions are in the second hypervariable region of the alpha 1-domain of the HLA-B13, B44, Bw52, and B49 antigens (B49 is quite rare in the Japanese population). The inflammatory region in UC patients was found to vary depending on their HLA-B alleles. These results suggest that the HLA-B locus itself plays an important role in the susceptibility to Japanese UC.
Assuntos
Colite Ulcerativa/genética , Antígenos HLA/genética , Adulto , Sequência de Aminoácidos , Suscetibilidade a Doenças , Feminino , Genes MHC Classe I , Genes MHC da Classe II , Ligação Genética , Genótipo , Teste de Histocompatibilidade , Humanos , Linfotoxina-alfa/genética , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de RestriçãoRESUMO
To evaluate the influence of the MHC-linked LMP7 gene on disease susceptibility in HLA class I and class II-associated diseases, the distribution of LMP7 alleles was determined using the PCR-RFLP method in 69 Japanese patients with Behçet's disease, 65 patients with sarcoidosis, and 100 unrelated healthy controls. No differences were found between either of the patient groups and the healthy control group, indicating that LMP7 allelic variation may not contribute to the pathogenesis of either Behçet's disease or sarcoidosis. We also analyzed linkage disequilibria between LMP7 and HLA class II alleles in Japanese populations.
Assuntos
Síndrome de Behçet/genética , Cisteína Endopeptidases , Complexo Principal de Histocompatibilidade/genética , Complexos Multienzimáticos , Polimorfismo Genético/genética , Proteínas/genética , Sarcoidose/genética , Alelos , Suscetibilidade a Doenças , Antígenos HLA-D/genética , Humanos , Japão , Desequilíbrio de Ligação/imunologia , Complexo de Endopeptidases do ProteassomaRESUMO
Sarcoidosis is a granulomatous disease showing a significant increase in the HLA-DR5, -DR6, and -DR8 associated alleles in Japanese. To investigate whether the class I antigen-processing genes, encoded within the MHC class II region between the HLA-DP and -DQ loci, are involved in determining the susceptibility to sarcoidosis, TAP1, TAP2, and LMP2 alleles were analyzed by the PCR-RFLP method in 85 Japanese patients with sarcoidosis and 91 healthy controls. There were no significant differences in the distribution of TAP1 and LMP2 alleles between the subgroups of the patients and controls positive or negative for DR5, DR6, and DR8. A significant decrease in the frequency of TAP2*0201 was found among the patients negative for DR5, DR6, and DR8 as compared to the DR-matched controls (p < 0.05), but this could be explained by its linkage disequilibrium to the negatively associated allele DR1. These findings suggest that the TAP or LMP2 gene is not primarily involved in the susceptibility to sarcoidosis. In the course of this study, a linkage disequilibrium was observed in the Japanese population between TAP1 and TAP2 alleles, TAP1*0201 and TAP2*0102.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/imunologia , Cisteína Endopeptidases , Polimorfismo Genético/imunologia , Proteínas/genética , Proteínas/imunologia , Sarcoidose/genética , Sarcoidose/imunologia , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Membro 3 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Alelos , Suscetibilidade a Doenças , Antígenos HLA-DR/genética , HumanosRESUMO
Behçet's disease (BD) is known to be associated with HLA-B51. In order to investigate the influence of the MICB gene, located about 120 kb centromeric of the HLA-B gene, on the susceptibility to BD, (CA/TG) dinucleotide repeat microsatellite polymorphism in intron 1 of the MICB gene was investigated among 77 Japanese patients with BD, 60 randomly selected controls and 28 HLA-B51-positive unrelated healthy controls. There was no significant difference in the phenotype frequency of the microsatellite polymorphism between the BD patients and controls. This result suggests that the MICB gene itself is not responsible for the development of BD, and that the candidate gene(s) for BD is located between the MICA and HLA-C genes.
Assuntos
Síndrome de Behçet/genética , Antígenos de Histocompatibilidade Classe I/genética , Repetições de Microssatélites , Polimorfismo Genético , DNA/análise , Primers do DNA/química , Suscetibilidade a Doenças , Antígenos HLA-C/genética , Humanos , Japão , Fenótipo , Distribuição AleatóriaRESUMO
Behçet's disease is associated with the HLA-B51 antigen. However, it has not yet been clarified if the HLA-B51 gene itself is the susceptibility gene related to this disease or if it is some other non-HLA gene in linkage disequilibrium with HLA-B51. Therefore, we screened one of the HSP70 genes, HUM70t (HSP70-Hom), around the class III region and the microsatellite sequence located between the HLA-B and TNF genes for genetic polymorphism in BD. A comparison between patients with BD and healthy controls revealed no significant difference in the frequency of the HUM70t polymorphism. In the microsatellite sequence, Tau-a, in the region between the HLA-B and TNF genes, the frequency of 14 repetitions of GT was increased significantly and that of 11 repetitions was decreased significantly in the patient group. Further, the allelic distributions of the B51 antigen-associated microsatellite polymorphism differed significantly between patients and healthy controls, and in the B51 antigen-negative subjects, analysis of the microsatellite polymorphism also revealed a significant difference in the haplotype frequency between the patient and control groups. These results suggest that the HLA-B51 gene may not be the primary locus responsible for BD, and implicate some other gene(s) located between the TNF and HLA-B genes.
Assuntos
Síndrome de Behçet/genética , DNA Satélite/imunologia , Antígenos HLA-B/genética , Polimorfismo Genético/imunologia , Fator de Necrose Tumoral alfa/genética , Sequência de Bases , Síndrome de Behçet/imunologia , Feminino , Proteínas de Choque Térmico HSP70/genética , Humanos , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
Previously, we reported a triplet repeat polymorphism in the transmembrane region within the MICA gene closely linked to HLA-B in a limited number of B27-positive Caucasian patients with ankylosing spondylitis (AS) (N = 48). In this study, we enrolled much more patients including some negative for B27, 162 AS subjects consisting of 140 B27-positive, and 22 B27-negative patients. The microsatellite allele consisting of 4 repetitions of (GCT/AGC) (A4 allele) was present at a significantly higher phenotype frequency in the patient group than in the ethnically matched control group (Pc < 0.000001). However, the frequency of the A4 allele was not significantly higher in the B27-positive and B27-negative patient groups, as compared to the B27-positive and B27-negative control groups, respectively. The higher phenotype frequency of the A4 allele in the patient group was supposed to be due to a strong linkage disequilibrium between the MICA and HLA-B genes. Thus, the possibility that the MICA gene is involved in the pathogenesis of AS can be excluded, supporting the hypothesis of a primary association of AS with HLA-B27.
Assuntos
Antígeno HLA-B27/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Polimorfismo Genético , Espondilite Anquilosante/genética , Repetições de Trinucleotídeos , População Branca/genética , Estudos de Casos e Controles , Frequência do Gene , Humanos , Espondilite Anquilosante/imunologiaRESUMO
Sarcoidosis is a multisystemic granulomatous disorder showing significant increases in the HLA-DRB1*11, *12, *14 and *08 alleles in the Japanese population. To evaluate the role of polymorphism in the DMA and DMB genes in predisposition to sarcoidosis, seventy Japanese patients with sarcoidosis and 95 unrelated healthy controls were analyzed in the third exon polymorphisms within the DMA and DMB genes by the PCR-RFLP method. There were no differences in the distribution of DMA alleles between the patient and control groups. The frequency of DMB*0102 was higher (p < 0.05) and that of DMB*0101 was lower (p < 0.05) in the patients than in the healthy controls. However, this association and negative association could be explained by linkage disequilibrium with the disease-associated DRB1 alleles. The DMA and DMB genes do not primarily confer the susceptibility to sarcoidosis.