RESUMO
BACKGROUND: Accurate pre-transplant prediction of late graft function remains an unmet need in kidney transplantation. The aim of this study was to evaluate HLA genes expression levels in pre-implantation biopsies (PIB) of deceased donor kidneys as markers for long-term graft outcome. METHODS: HLA genes expression analysis was initially performed using microarray data of 53 PIB, previously generated by our laboratory. The validation analysis was performed by real-time PCR in 116 PIB from an independent cohort. RESULTS: The microarray data showed association between high expression levels of HLA class II genes, especially HLA-DQB1 and -DQB2, in kidneys from young (18 to 49-year-old) donors and poor (eGFRâ¯<â¯45â¯mL/min/1.73â¯m2) 1- and 5-year graft function. A subsequent study in an independent cohort, in which only HLA-DQB2 expression was evaluated, validated the association between increased HLA-DQB2 expression in PIB of kidneys from young donors and poor 1-year graft function: expression levels ≥0.0025 relative units conferred an odds ratio of 22.5, with positive and negative predictive values of 71.4% and 90.0%, respectively. CONCLUSION: Heightened expression of HLA-DQB1 and -DQB2 in PIB are promising tools for pre-transplant risk assessment of poor late graft function in transplants with kidneys from 18 to 49-year-old donors.
Assuntos
Rejeição de Enxerto/diagnóstico , Antígenos HLA-DQ/metabolismo , Cadeias beta de HLA-DQ/metabolismo , Transplante de Rim , Rim/metabolismo , Complicações Pós-Operatórias/diagnóstico , Adolescente , Adulto , Biópsia , Feminino , Rejeição de Enxerto/etiologia , Antígenos HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Risco , Regulação para Cima , Adulto JovemRESUMO
The aim of this study was to analyze the HLA class II alleles in neuromyelitis optica (NMO) and MS patients from Rio de Janeiro to clarify whether the pattern of genetic predisposition in NMO is different from the one seen in MS or whether it is possible to determine specific alleles of susceptibility or resistance. The DR3 haplotype was over represented in NMO while the DR15 was over represented in MS. The HLA-DRB1*03:01 allele was associated with NMO regardless the NMO-IgG status but did not influence the long term disability. The comparison of the allele and haplotype frequencies significantly discriminated patients with NMO vs. MS.
Assuntos
Cadeias HLA-DRB1/genética , Imunoglobulina G/metabolismo , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Neuromielite Óptica/genética , Neuromielite Óptica/imunologia , Adolescente , Adulto , Idoso , Brasil , Estudos de Casos e Controles , Criança , Análise Mutacional de DNA , Feminino , Genótipo , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Cadeias beta de HLA-DQ/metabolismo , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Neuromielite Óptica/diagnóstico por imagem , Fenótipo , Índice de Gravidade de Doença , Adulto JovemRESUMO
A high proportion of human recurrent spontaneous abortions (RSA) remain unexplained. The possible association between RSA and different genetic polymorphisms within the human leucocyte antigen system (HLA system, the human major histocompatibility complex) has been investigated with conflicting results since many decades. Here, we describe a case-control study with 136 Southern Brazilian women of predominantly European ancestry (75 control and 61 cases with unexplained RSA). We investigated the relationship between unexplained RSA and alleles and genotypes from two classical loci of the HLA: HLA-DRB1 and HLA-DQB1, as well as three loci related to cytokine production and their serum levels: TNFA (-308G>A), IL10 (-1082G>A, -819T>C, -592A>C) and IFNG (+874A>T). Genotyping was performed by an allele-specific PCR method. While all results concerning cytokine-related genes turned out to be negative, we found the genotype HLA-DQB1*02:02, 03:01 to be significantly decreased and the allele HLA-DRB1*11:04 to be significantly increased among patients.
Assuntos
Aborto Habitual/genética , Antígenos de Histocompatibilidade Classe II/genética , Polimorfismo Genético , Aborto Habitual/metabolismo , Adulto , Brasil , Estudos de Casos e Controles , Citocinas/genética , Citocinas/metabolismo , Feminino , Frequência do Gene , Genótipo , Cadeias beta de HLA-DQ/genética , Cadeias beta de HLA-DQ/metabolismo , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/metabolismo , Humanos , Fenótipo , GravidezRESUMO
BACKGROUND AND OBJECTIVE: Risk haplotypes have been described in celiac disease (CD), but the influence of native genes on CD in Hispanic Americans is unknown. The aim of the study was to measure the frequency of Amerindian mitochondrial DNA (mtDNA) haplogroups (inherited by the maternal line) in mixed-blood patients with CD from Chile, Argentina, and Uruguay, and to assess the relation between these and human leukocyte antigen (HLA) alleles and haplotypes and clinical presentations. PATIENTS AND METHODS: Clinical history, histological data, and genetic studies were conducted following 2 protocols: a case-control study of 72 Chilean patients with CD and controls, and an assessment of 43 (additional) samples of celiac patients from Chile, 96 from Argentina, and 57 from Uruguay, compared with the mtDNA frequency in the corresponding country. HLA typing was performed by a commercial kit, and mtDNA was determined by means of polymerase chain reaction and restriction fragment length polymorphisms analysis. RESULTS: A total of 73.6% of cases had typical presentations. The most frequent HLA alleles were HLA-DQB*201 and 202. No-DQ2/DQ8 HLA haplotypes were found in 7% of cases. mtDNA frequencies for typical Amerindian haplogroups were found in 71% of cases and 64% of controls (P χ2 = 0.016); in the comparative analysis, mtDNA distribution was not different from the figures reported for the respective general country population. No relation was found between haplotypes or haplogroups and clinical presentations. CONCLUSIONS: mtDNA haplogroups A/B/C/D were frequently found in celiac patients and controls, but no relations appeared between haplogroups, haplotypes, and clinical presentations.