RESUMO
Autoimmune hepatitis is an immune cell-mediated chronic liver disease of unknown cause that leads, when untreated, to cirrhosis and liver failure. Importantly, this disease affects not only adults but children as well. Genetic susceptibility is clearly important and the major susceptibility factor identified up to now is the HLA-DRB1 locus, but other genes may play a role as well. HLA-DRB1 alleles present in South American patients differ from those found in patients in other parts of the world. In addition, we have recently identified two chromosomal regions where additional susceptibility factors may be found in Brazilian patients, namely, the class III MHC region and the 5q31 region where the IL-4 and IL-13 genes are located. This review discusses the current knowledge of the pathogenesis of this autoimmune disease occurring in the setting of an immune-privileged organ, the liver, and compares the data on gene polymorphisms studied in Brazil and in other parts of the world.
Assuntos
Hepatite Autoimune/epidemiologia , Hepatite Autoimune/imunologia , Brasil/epidemiologia , Hepatite Autoimune/classificação , Hepatite Autoimune/genética , HumanosRESUMO
The major histocompatibility complex (MHC) class I chain-related A (MICA) gene, located near HLA-B, codes for protein products with structural similarities to those of classical MHC class I genes, but which neither bind beta(2)-microglobulin nor present peptide. Expressed predominantly on gastrointestinal and tumour epithelial cells, they are stress-induced and interact with C-type lectin like receptor (NKG2D) on gammadelta, alphabeta CD8+ T cells and natural killer (NK) cells. MICA is highly polymorphic, with 54 extracellular allelic sequences described. We typed 200 healthy subjects in a sample of the São Paulo population by extended polymerase chain reaction-sequence-specific primers (PCR-SSP) to characterize the MICA polymorphism and analysed MICA/HLA-B linkage disequilibrium. The MICA*008 group (g) was predominant (47%), with several HLA-B associations. Rare combinations MICA*008g-HLA-B37, MICA*008g-B72 and MICA*010-HLA-B52 were detected. Given the extent of this polymorphism and its possible relevance for disease association, we determined MICA and HLA-B alleles in 33 Behçet's patients, in an attempt to clarify the associated genetic marker. Our results showed an increase of MICA*006, but not MICA*009, in the patient group (6/33) compared with controls (3/200) (18.2% vs. 1.5%; P(c) = 0.005). Both alleles were always in association with HLA-B51, suggesting that HLA-B is indeed the primary susceptibility locus (P = 0.00008) and that MICA*006 may be an additional risk factor.
Assuntos
Antígenos de Histocompatibilidade Classe I/genética , Polimorfismo Genético , Brasil , Frequência do Gene , Genética Populacional , Antígenos HLA-B/genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Fenótipo , Reação em Cadeia da Polimerase/métodosRESUMO
Uma análise do perfil dos antígenos HLA de classe II numa amostra da populaçäo de Säo Paulo é descrita neste trabalho. Os dados foram obtidos através de técnicas de amplificaçäo gênica utilizando-se iniciadores seqüências-específicos para HLA-DRB (PCR-SSP) ou amplificaçäo gênica seguida de hibridaçäo com oligonucleotídeos específicos (PCR-SSOP) para HLA-DQA e DQB. Foram calculadas as freqüências gênicas e as freqüências haplotípicas DRB-DQB e DQA-DQB e a populaçäo mostrou estar em equilíbrio genético de acordo com a lei de Hardy-Weinberg. Finalmente, comparamos também os dados obtidos com os da populaçäo de Porto Velho, Rondônia, salientando a importância da obtençäo de dados regionais para os controles quando se estuda este complexo sistema genético.