RESUMO
The novel HLA-DPB1*14:01:15 allele differs from DPB1*14:01:01:01 by change of C > T in exon 3.
Assuntos
Alelos , Sequência de Bases , Éxons , Cadeias beta de HLA-DP , Teste de Histocompatibilidade , Doadores de Tecidos , Humanos , Cadeias beta de HLA-DP/genética , Brasil , Análise de Sequência de DNA/métodos , Medula Óssea , Alinhamento de Sequência , Códon , Transplante de Medula ÓsseaRESUMO
The new HLA-DRB3*03:69 allele differs from DRB3*03:01:01:03 by change of C â G in exon 3.
Assuntos
Alelos , Éxons , Cadeias HLA-DRB3 , Sequenciamento de Nucleotídeos em Larga Escala , Teste de Histocompatibilidade , Humanos , Sequência de Bases , Códon , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Teste de Histocompatibilidade/métodos , Cadeias HLA-DRB3/genética , Alinhamento de Sequência , Análise de Sequência de DNA/métodosRESUMO
HLA-DQB1*02:211 allele differs from DQB1*02:02:01:02 by change of C â A in exon 2.
Assuntos
Alelos , Éxons , Cadeias beta de HLA-DQ , Doadores de Tecidos , Humanos , Cadeias beta de HLA-DQ/genética , Brasil , Teste de Histocompatibilidade , Transplante de Medula Óssea , Sequência de Bases , Análise de Sequência de DNA/métodos , Códon , Medula ÓsseaRESUMO
BACKGROUND: A distinct phenotype in Coronavirus disease 2019 (Covid-19) was observed in severe patients, consisting of a highly impaired interferon (IFN) type I response, an exacerbated inflammatory response. OBJECTIVE: The aim of the present study was to investigate a possible association of single nucleotide polymorphisms (SNPs), in five genes related to the immune response, rs3775291 in TLR3; rs2292151 in TICAM1; rs1758566 in IFNA1; rs1800629 in TNF, and rs1800795 in IL6 with the severity of Covid-19. METHODS: A cross-sectional study was performed, with non-severe and severe/critical patients diagnosed with Covid-19, by two public hospitals in Brazil. In total, 300 patients were genotyped for the SNPs, 150 with the non-severe form of the disease and 150 with severe/critical form. RESULTS: The T/T genotype of TLR3 in recessive model shows 58% of protection against severe/critical Covid-19; as well as the genotypes G/A+A/A of TICAM1 in dominant model with 60% of protection, and in a codominant model G/A with 57% and A/A with 71% of protection against severe/critical Covid-19. Comparing severe and critical cases, the T/C genotype of IFNA1 in the codominant model and TC+C/C in the dominant model showed twice the risk of critical Covid-19. CONCLUSION: We can conclude that rs3775291, rs2292151 and rs1758566 can influence the COVID-19 severity.
Assuntos
COVID-19 , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , SARS-CoV-2 , Índice de Gravidade de Doença , Receptor 3 Toll-Like , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Brasil/epidemiologia , COVID-19/genética , COVID-19/virologia , Estudos Transversais , Genótipo , Interferon Tipo I/genética , Interferon-alfa , SARS-CoV-2/genética , Receptor 3 Toll-Like/genéticaRESUMO
The new HLA-DPA1*01:182 allele differs from HLA-DPA1*01:03:01:04 by a single mismatch in exon 4.
Assuntos
Medula Óssea , Cadeias alfa de HLA-DP , Humanos , Alelos , Brasil , Teste de HistocompatibilidadeRESUMO
We identified two new HLA-DRB3 alleles in Brazilian individuals using next generation sequencing.
Assuntos
Medula Óssea , Humanos , Cadeias HLA-DRB3 , Alelos , BrasilRESUMO
HLA-A*68:190:02 differs from A*68:190:01 by a single synonymous nucleotide change in exon 2.
Assuntos
Medula Óssea , Humanos , Alelos , Brasil , Éxons/genéticaRESUMO
Four new HLA-B alleles were identified in Brazilian individuals using next generation sequencing.
Assuntos
Medula Óssea , Doadores de Tecidos , Humanos , Brasil , Alelos , Transplante de Medula Óssea , Sequenciamento de Nucleotídeos em Larga Escala , Antígenos HLA-B/genéticaRESUMO
Killer cell immunoglobulin-like receptors (KIR) exhibit extensive diversity, giving rise to different KIR profiles in populations worldwide. This study aimed to investigate the distribution of KIR genes and HLA ligands in a population from Campinas, southeastern Brazil (n = 292), and to compare their results with other populations. A comprehensive analysis of population-specific genes, genotype, and haplotype frequencies of KIR may facilitate a better understanding of their evolution and role in immunity. The genotyping of 16 KIR genes and HLA class I alleles was performed by the reverse sequence-specific oligonucleotide methodology using the Luminex platform (One Lambda, Inc., Canoga Park, CA). The framework genes were present in all individuals, with the most common non-framework KIR genes detected being KIR2DP1(96.6%), KIR2DL1(95.5%), KIR3DL1(94.5%), KIR2DS4(93.8%) and KIR2DL3(87.3%). KIR2DS1, KIR2DS3, KIR2DS5, and KIR3DS1 presented frequencies below 40%. KIR2DL2, KIR2DL5, and KIR2DS2 showed intermediate frequencies (between53% and 58%). The activating gene KIR2DS5 was the least common in this population (30.8%). Forty-five KIR profiles were found with the commonest being the homozygous A haplotype (27.4%). The distribution of KIR genes in the Brazilian population is similar to Caucasian European and Euro-descendant populations.
Assuntos
Receptores KIR , Humanos , Brasil , Frequência do Gene , Ligantes , Receptores KIR/genética , GenótipoRESUMO
It was demonstrated that effervescent glutamine supplementation in HIV+ individuals treated with antiretroviral therapy (ART) increased CD4+ T lymphocytes, decreased inflammation biomarkers, and brought health benefits. This pilot study aimed to explore serum metabolite variations in the HIV+ group under ART after 30 days of supplementation with glutamine, and in comparison to the matched HIV- group. The group of HIV+ showed lower levels of choline, creatine, pyruvate, glutamate, lysine, and tyrosine when compared to the HIV- group. Glucose, lipids, lactate, glutamine, phenylalanine, threonine, and phenylalanine/tyrosine were higher in HIV+ patients under long ART. Serum metabolome variations were shown to be consistent with the health improvements observed in the HIV+ group after effervescent glutamine supplementation, which might aid in ART in HIV+ individuals.
Assuntos
Glutamina , Infecções por HIV , Humanos , Glutamina/uso terapêutico , Projetos Piloto , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Tirosina/uso terapêutico , Fenilalanina/uso terapêutico , Administração OralRESUMO
Abstract The aim of this study was to evaluate tumor necrosis factor alpha (TNF-α), interleukin (IL)- 17A/F levels in the serum of ankylosing spondylitis (AS) patients after anti-TNF therapy, in order to understand how these cytokines are involved in this therapeutic response. Forty-four AS patients were included in the study: thirty using anti-TNF therapy were classified according to their therapy response as responders (15) and non-responders (15) and 14 without anti-TNF therapy were classified as AS control. Fifteen healthy individuals formed the control group. Serum levels of TNF-α were determined using Luminex technology and for IL-17A and IL-17F using ELISA. The non-responder patients presented higher serum levels of TNF-α than the responders and AS control; the same results were found when HLA-B*27 positive or negative patients were separately analyzed. IL-17A and IL17F serum levels were similar for all groups. According to the clinical disease activity, AS patients with BASDAI ≥4 had higher serum levels of TNF-α than AS patients with BASDAI <4. Positive correlation was found between TNF-α levels and BASDAI. In AS patients, TNF-α serum levels were associated with anti-TNF therapy and disease activity independently of HLA-B*27, and IL-17A and IL-17F were not related to anti-TNF treatment
Assuntos
Humanos , Masculino , Feminino , Pacientes/classificação , Espondilite Anquilosante/patologia , Fator de Necrose Tumoral alfa/análise , Interleucina-17/análise , Polimorfismo Genético , Citocinas/classificação , Estudos de Associação Genética/instrumentaçãoRESUMO
BACKGROUND: Blood transfusions usually result in the production of alloantibodies, complicating subsequent transfusions. Many blood group systems, in addition to ABO and Rh, can lead to the production of irregular antibodies in multiple transfused patients. OBJECTIVES: The aim of this work was to standardize a molecular biology methodology for identified some alleles of KEL, FY, JK and DI blood group system; the transfusion efficacy of chronically transfused patients with phenotype-matched blood was also evaluated. METHODS: A PCR-SSP was developed and validated using Sanger sequencing. The genotype and frequencies of 141 multiple transfused patients treated at blood banks of Maringá were compared with the blood donor's population to assess the availability of compatible blood bags. The clinical history of 29 patients on a phenotype-compatible transfusion regimen was followed to assess pre- and post-genotyping alloimmunization. RESULTS: The PCR-SSP was effective in identifying the genotypes under study. Significant differences were observed in genotype and allele frequencies for FY and JK. Compatible bags were identified for all patients. Most patients (93.1%) did not develop new alloantibodies after erythrocyte genotyping. CONCLUSION: Erythrocyte genotyping proved to be important both in the search for positive blood bags for rare alleles and in the prevention of alloimmunization.
RESUMO
Leprosy is a chronic disease and also a global health issue, with a high number of new cases per year. Toll-like receptors can respond to mycobacterial molecules in the early stage of infection. As important components of the innate immune response, alterations in genes coding for these receptors may contribute to susceptibility/protection against diseases. In this context, we used a case-control study model (183 leprosy cases vs. 185 controls) to investigate whether leprosy patients and the control group, in southern Brazil, have different frequencies in TLR1 (TLR1 G>T; rs5743618), TLR2 (TLR2 T>C, rs1816702 and rs4696483), and TLR4 (TLR4 A>G, rs1927911) polymorphisms. Analysis of the TLR1 1805G>T polymorphism presented the G/G genotype more frequently in the control group. TLR2 T>C rs1816702 and TLR2 T>C rs4696483, the T/T and C/T genotype, respectively, were more frequent in the control group than in leprosy patients, suggesting protection from leprosy when the T allele is present (rs4696483). Haplotype analyses between TLR1 (rs5743618) and TLR2 (rs1816702 and rs4696483) polymorphisms suggest risk for the presence of the TCC haplotype and protection in the presence of the TCT haplotype. This study suggests that polymorphisms in TLR1 and TLR2 are factors that may contribute to development/resistance of leprosy.
RESUMO
BACKGROUND: Zika virus (ZIKV) is an emerging arbovirus associated with foetal malformations and neurological complications. The infection is usually associated with mild symptoms. The comparison between the allelic frequency of polymorphic genes in symptomatic infected individuals in the population can clarify the pathogenic mechanisms of ZIKV. During ZIKV infection, cytokines are produced and natural killer (NK) cells are recruited, whose activation depends on signaling pathways activated by specific receptors, such as killer cell immunoglobulin-like receptors (KIR). These molecules interact with human leukocyte antigen (HLA) class I ligands and are encoded by polymorphic genes. OBJECTIVES: This study aimed to evaluate the frequency of allelic variants of the genes encoding the KIR receptors and their HLA class I ligands in 139 symptomatic ZIKV-patients and 170 controls negative for the virus, and to evaluate the role of these variants for ZIKV susceptibility. METHODS: KIR and HLA class I genes were genotyped using the polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) technique. FINDINGS: No significant differences in the frequency distribution of KIRs and KIR-HLA in patients compared to controls were observed. MAIN CONCLUSIONS: KIR and its HLA ligands might play a minor role in ZIKV infection in the south and southeast Brazilian individuals.
Assuntos
Infecção por Zika virus , Zika virus , Brasil , Frequência do Gene/genética , Genótipo , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Ligantes , Receptores KIR/genética , Zika virus/genética , Infecção por Zika virus/genéticaRESUMO
During the 2015-2016 epidemic, Brazil was the country with the highest rate of Zika virus (ZIKV) infection in the Americas. Twenty-nine percent of pregnant women positive for ZIKV exhibited ultrasound scans with fetus anomalies. Human leukocyte antigen-G (HLA-G) exerts immunoregulatory effects by binding to inhibitory receptors, namely LILRB1 and LILRB2, thus preventing mother-fetus rejection and vertical pathogen transmission. The binding of HLA-G to one of its receptors modulates both innate and adaptive immunity. However, in a viral infection, these molecules may behave as pathogenic mediators shifting the pregnancy environment from an anti-inflammatory profile to a pro-inflammatory phenotype. Genetic mutations might be associated with the change in phenotype. This study aimed to explore the possible role of polymorphic sites in HLA-G, LILRB1 and LILRB2 in mother-fetus ZIKV transmission. Polymorphisms were detected by direct sequencing. Differences in allele and/or genotype frequencies for each SNP analyzed among ZIKV non-transmitting and transmitting mother-child pairs, among ZIKV-transmitting and non-transmitting mothers and between ZIKV-infected and non-infected children were compared by Mid-P exact test or Yates' correction. Significant susceptibility of ZIKV vertical transmission is suggested in ZIKV-transmitting and non-transmitting mothers and ZIKV-infected and non-infected children for LILRB1_rs1061684 T/T (p = 0.03, Pc = 0.06, OR = 12.4; p = 0.008, Pc = 0.016, OR = 16.4) and LILRB1_rs16985478 A/A (p = 0.01, Pc = 0.02, OR = 19.2; p = 0.008, Pc = 0.016, OR = 16.4). HLA-G_rs1710 (p = 0.04, Pc = 0.52, OR = 4.30) was also a susceptibility factor. LILRB2_rs386056 G/A (p = 0.02, Pc = 0.08, OR = 0.07), LILRB2_rs7247451 G/G (p = 0.01, Pc = 0.04, OR = 0.04) and HLAG_rs9380142 T/T (p = 0.04, Pc = 0.52, OR = 0.14) were suggested as protective factors against vertical transmission. The current study suggests that polymorphic sites in the LILRB1 and HLA-G genes might be associated with mother-to-child ZIKV transmission while LILRB2 might be associated with protection against ZIKV transmission in the womb in a population from the south and southeast of Brazil.
RESUMO
BACKGROUND Zika virus (ZIKV) is an emerging arbovirus associated with foetal malformations and neurological complications. The infection is usually associated with mild symptoms. The comparison between the allelic frequency of polymorphic genes in symptomatic infected individuals in the population can clarify the pathogenic mechanisms of ZIKV. During ZIKV infection, cytokines are produced and natural killer (NK) cells are recruited, whose activation depends on signaling pathways activated by specific receptors, such as killer cell immunoglobulin-like receptors (KIR). These molecules interact with human leukocyte antigen (HLA) class I ligands and are encoded by polymorphic genes. OBJECTIVES This study aimed to evaluate the frequency of allelic variants of the genes encoding the KIR receptors and their HLA class I ligands in 139 symptomatic ZIKV-patients and 170 controls negative for the virus, and to evaluate the role of these variants for ZIKV susceptibility. METHODS KIR and HLA class I genes were genotyped using the polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) technique. FINDINGS No significant differences in the frequency distribution of KIRs and KIR-HLA in patients compared to controls were observed. MAIN CONCLUSIONS KIR and its HLA ligands might play a minor role in ZIKV infection in the south and southeast Brazilian individuals.
RESUMO
HLA-B*27 is an important marker for spondyloarthritis (SpA), however, many SpA patients are HLA-B*27 negative. Thus, the aim of this study was to investigate the influence of IL17, TNF and VDR gene polymorphisms in SpA patients who were HLA-B*27 negative. This case-control study was conducted in 158 patients [102 patients with ankylosing spondylitis (AS) and 56 with psoriatic arthritis (PsA)] and 184 controls. HLA-B*27 genotyping was performed using PCR-SSP and IL17A (rs2275913), IL17F (rs763780), TNF-308 (rs1800629), TNF-238 (rs361525), FokI C>T (rs2228570), TaqI C>T (rs731236), ApaI A>C (rs7975232), and BsmI C>T (rs1544410) using PCR-RFLP. Statistical analyses were performed by Chi-square and logistic regression using OpenEpi and SNPStats software. The IL17F C allele frequency was higher in patients with SpA, AS and PsA compared to controls. The IL17F T/C genotype frequency was higher in SpA patients in an overdominant inheritance model and when men and women were separately analyzed. IL17A_IL17F AC haplotype was significantly associated to the risk for SpA patients. As for VDR, the ApaI a/a was a potential risk factor for SpA in men. In conclusion, IL17F C variant contributed to the risk of SpA in Brazilian patients who were HLA-B*27 negative and could be a potential marker for SpA.
RESUMO
Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease that mainly affects the axial and sacroiliac joints. Single-nucleotide polymorphisms (SNPs) in genes encoding cytokines have been associated with AS, which can interfere with the production of these cytokines and contribute to the development of AS. In order to contribute to a better understanding of the pathology of AS, our objective was to investigate a possible association of the IL10 -1082 A>G SNP (rs1800896) with AS and to evaluate the serum levels of TNF-α, IL-10, IL-17A, and IL-17F in AS patients and controls comparing them with their respective genotypes (TNF rs1800629, IL10 rs1800896, IL17A rs2275913, and IL17F rs763780). Patients and controls were selected from the Maringá University Hospital and the Maringá Rheumatism Clinic, in Paraná State, Southern Brazil, and they were diagnosed by the ASAS Criteria. In total, 149 patients and 169 controls were genotyped for the IL10 -1082 A>G polymorphism using a polymerase chain reaction with sequence specific primers (PCR-SSP); the measurement of TNF-α serum levels was performed through the immunofluorimetric test and IL-10, IL-17A, and IL-17F using an ELISA test. There was a high frequency of the IL10 -1082 G allele in AS patients compared with controls with an odds ratio of 1.83 and 95% confidence interval of 1.32 to 2.54, and a significant difference in the genotype frequencies of the IL10 -1082 A/G+G/G between patients and healthy controls, with an odds ratio of 3.01 and 95% confidence interval of 1.75 to 5.17. In addition, increased serum levels of IL-10 were observed in AS patients: 2.38 (IQR, 0.91) pg/ml compared with controls 1.72 (IQR 0.93) pg/ml (P = 0.01). Our results also showed an association between IL17F rs763780 C/T+T/T genotypes and increased serum levels of IL-17F in patients with AS and also in controls. We can conclude that patients with the A/G and G/G genotypes for -1082 A>G (rs1800896) in the IL10 gene are three times more likely to develop AS, that the serum level of IL-10 was higher in AS patients and that the IL17F rs763780 polymorphism can affect the levels of IL-17F in the serum of patients and controls in the same way.
Assuntos
Predisposição Genética para Doença , Interleucina-10/genética , Espondilite Anquilosante/genética , Adulto , Alelos , Brasil , Estudos de Casos e Controles , Feminino , Frequência do Gene , Humanos , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-17/sangue , Interleucina-17/imunologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Espondilite Anquilosante/sangue , Espondilite Anquilosante/imunologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Toll-like receptors (TLRs) are a family of transmembrane receptors whose signaling control cellular processes of cell proliferation, survival, apoptosis, angiogenesis, remodeling, and repair of tissues. Polymorphisms in TLR genes can change the balance between pro and anti-inflammatory cytokines, modulating the risk of infection, chronic inflammation, and cancer. Although many studies have demonstrated the direct involvement of TLR signaling in the benefit of tumor cells in certain cancers, little is known about the influence of these gene polymorphisms on myeloproliferative neoplasms (MPNs). In this context, the objective of the study was to investigate a possible association between the TLR polymorphisms and the development of MPNs. 167 patients diagnosed with MPN and 222 healthy controls from the same region were evaluated. Genomic DNA was extracted and the TLR2 (rs5743708), TLR4 (rs4986790, rs4986791), TLR9 (rs5743836, rs187084) and JAK2V617F polymorphisms were genotyped by PCR-RFLP. The statistical analysis was performed by OpenEpi and SNPstat software. The JAK2V617F mutation was found in 68.32% of patients. TLR9-1486C/T CT genotype was less frequent in patients with polycythemia vera (PV) (OR 0.39, 95% CI 0.20-0.78, P = 0.025). When haplotype frequencies were analyzed, -1237T/-1486C (TLR9) was also less frequent in men (OR 0.58, 95% CI 0.36-0.94) and JAK negative men patients (OR 0.43, 95% CI 0.21-0.88). We can infer that the TLR9-1486 CT genotype could be associated with protection for PV and the TLR9-1237T/-1486C haplotype, protection for men, as well as for JAK negative men patients with MPN. There were no associations between TLR2 and TLR4 gene polymorphisms and MPN.
Assuntos
Neoplasias da Medula Óssea/genética , Janus Quinase 2/genética , Receptor Toll-Like 9/genética , Receptores Toll-Like/genética , Adulto , Idoso , Neoplasias da Medula Óssea/metabolismo , Feminino , Haplótipos/genética , Humanos , Janus Quinase 2/metabolismo , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/genética , Policitemia Vera/genética , Polimorfismo de Nucleotídeo Único/genética , Mielofibrose Primária/genética , Trombocitemia Essencial/genética , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Receptor Toll-Like 9/metabolismo , Receptores Toll-Like/metabolismoRESUMO
Endometriosis (EDT) is an inflammatory disease characterized by implantation/growth of endometrial tissue, glands, and/or stroma, outside the uterus. Reduced NK cell cytotoxic activity has been implicated in its pathogenesis, together with other immunologic alterations. We investigated the influence of KIR gene polymorphisms and their HLA ligand combinations in deep endometriosis (DE) susceptibility. One hundred sixty women with a histological diagnosis of DE and 202 control women without the disease, who underwent laparoscopy, were enrolled. The DE group was subdivided into initial (I/II; n = 60) and advanced stages (III/IV, n = 100). KIR and HLA class I gene polymorphisms were typed by PCR-SSP and sequence-based-typing (SBT), respectively. We observed a significant association of KIR2DL2, an inhibitory gene of B haplotype, conferring risk for DE in Euro-descendants. Positive associations of Bx haplotype and centromeric AB segments were also found. However, no association with KIR-HLA ligand combination was observed. Our data suggest KIR2DL2 gene to be a relevant factor favoring NK inhibition in DE in Euro-descendants, contributing to the defective NK cytotoxic activity and impaired clearance of ectopic endometrial cells in the disease.