CD4 T cells from patients with type 2 AIH positive for the predisposing HLA allele DRB1*0701 recognize seven regions of CYP2D6, five of which are also recognized by CD8 T cells.
These findings suggest that the DR4-specific sequence (Val 11 and His 13 at amino acid positions 11 and 13, respectively), but not particular Dw-associated DR4 sequence, in the first domain of the DRB1 chain contributes to susceptibility to autoimmune hepatitis among Japanese.
The genetic AIH risk factor HLA DRB1*03:01 was more frequent in younger patients, and DRB1*04:01 was more frequent in middle-aged patients without an obvious link to virus seropositivities.
The aim of this study was to determine the association of TNF-α (-308 G > A) polymorphism with AIH susceptibility and with TNF-α expression or clinical manifestations of AIH.
A polymorphism of the tumor necrosis factor gene occurs more commonly in patients with type 1 autoimmune hepatitis than in normal subjects; it is associated with a poorer response to corticosteroids.
In conclusion, our data indicate that type 1 AIH predisposition in a Venezuelan mestizo population of different ethnic backgrounds is associated with DRB1*1301 and DRB1*0301 alleles.
Two types of autoimmune hepatitis are justified by serological markers, but they also have distinctive genetic associations (DRB1 and DQB1 genes) and autoantigens.
The detailed internal replication and parallel analyses allowed the observation of two of eight AIH cases carrying a rare allele genotype for a previously described AIH-associated gene (FTCD), plus multiple occurrences of known HLA-DRB1 alleles associated with AIH (HLA-DRB1-03:01:01, 13:01:01 and 7:01:01).
The DRB1*0405-DQB1*0401 haplotype in autoimmune pancreatitis showed no significant association with any HLA class I antigens, in contrast to the B54-DRB1*0405-DQB1*0401 haplotype reported in autoimmune hepatitis.
CD4 T cells from patients with type 2 AIH positive for the predisposing HLA allele DRB1*0701 recognize seven regions of CYP2D6, five of which are also recognized by CD8 T cells.
Increased frequencies of both HLA-DRB1*04:04:01 and *16:02:01:01 alleles (OR = 2.91; 95% CI = 1.08-7.84) and the haplotype (DRB1-TNFA-LTA) *04:04:01-G-A (OR = 5.33; 95% CI = 1.32-21.49) were observed in AIH patients.
The DRB1*0405-DQB1*0401 haplotype in autoimmune pancreatitis showed no significant association with any HLA class I antigens, in contrast to the B54-DRB1*0405-DQB1*0401 haplotype reported in autoimmune hepatitis.
The frequency of deleterious alleles in TNFAIP3 was higher in the AIH subset without the DRB1 risk alleles than that with (P = 0.0052, OR 5.10, 95%CI 1.55-16.74).
Among the HLA DRB1 alleles, DRB1*0301 (20% vs 6.19%; P = 0.03), DRB1*1301 (15% vs 2.65%; P = 0.01), DRB1*14 (30% vs 11.5%; P = 0.02) and DRB1*1501 (40% vs 22.12%; P = 0.08) were increased in AIH patients when compared with the controls.
The DRB1*04:05-DQB1*04:01 haplotype was significantly associated with AIH susceptibility (30% vs. 11%, P = 1.2×10(-10); odds ratio [OR] = 3.51) and correlated with elevated serum IgG (3042 vs. 2606 mg/dL, P = 0.041) and anti-smooth muscle antigen positivity (77% vs. 34%, P = 0.000006).
Increased frequencies of both HLA-DRB1*04:04:01 and *16:02:01:01 alleles (OR = 2.91; 95% CI = 1.08-7.84) and the haplotype (DRB1-TNFA-LTA) *04:04:01-G-A (OR = 5.33; 95% CI = 1.32-21.49) were observed in AIH patients.
Susceptibility for type 1 autoimmune hepatitis has been associated with the major histocompatibility alleles DRB1*0301, DRB3*0101, DRB1*0401, and DRB4*0103, whereas the DRB1*1501 allele may protect from the disease.