TY - JOUR
T1 - Pediatric and adult forms of type I autoimmune hepatitis in Argentina
T2 - Evidence for differential genetic predisposition
AU - Pando, Marcelo
AU - Larriba, Julian
AU - Fernandez, Gabriela C.
AU - Fainboim, Hugo
AU - Ciocca, Mirta
AU - Ramonet, Margarita
AU - Badia, Isabel
AU - Daruich, Jorge
AU - Findor, Jorge
AU - Tanno, Hugo
AU - Canero-Velasco, Cristina
AU - Fainboim, Leonardo
PY - 1999
Y1 - 1999
N2 - The aim of this study was to compare major histocompatibility complex (MHC) class II susceptibility to type 1 autoimmune hepatitis (AH) between children and adults of the same ethnic group. HLA-DRB1, HLA-DRB3, HLA-DQA1, and HLA-DQB1 gene subtypes were examined by high resolution oligonucleotide typing in 122 pediatric (PAH) and 84 adult (AAH) patients and in 208 controls. In children, HLA-DRB1*1301 was the primary susceptibility allele (66.4% patients vs. 10.6% controls, relative risk [RR] = 16.3, Pc < 10-24) whereas HLA-DRB1*1302, which differs from HLA-DRB1*1301 by only 1 amino acid, appeared to be protective. The exclusion of individuals with HLA- DRB1*1301 from control and pediatric patients allowed us to find a secondary association of PAH with HLA-DRB1*0301. Possession of HLA-DRB1*1301, however, was associated with a lower therapeutic response rate. Analysis of peptide binding pocket residues indicated that Tyr 10, Ser 11, Ser 13, and Val 86 in the class II β chain were present in 85% of patients compared with 37% of controls, suggesting that a high proportion of AH susceptibility is attributable to these residues (etiologic fraction [EF] = 76%). In contrast to the class II associations in children, AAH was associated with HLA- DRB1*0405 (RR = 10.4, Pc < .005) but not with HLA-DRB1*1301 or HLA- DRB1*0301. In addition, HLA-DR4 with the class I gene, HLA-A11, appeared synergistic in predisposing AAH patients to develop extra-hepatic autoimmune (AI) manifestations (odds ratio [OR] = 104.9, Pc < 10-4). Concomitant differences in autoantibody profiles were also observed in PAH versus AAH: smooth muscle antibodies (SMA) were most prevalent in PAH but antinuclear antibodies were most prevalent in AAH (P = .003). This study therefore reveals that different HLA-DRB1 allotypes confer susceptibility to AH in children and adults and raises the possibility that PAH and AAH may be triggered by different factors.
AB - The aim of this study was to compare major histocompatibility complex (MHC) class II susceptibility to type 1 autoimmune hepatitis (AH) between children and adults of the same ethnic group. HLA-DRB1, HLA-DRB3, HLA-DQA1, and HLA-DQB1 gene subtypes were examined by high resolution oligonucleotide typing in 122 pediatric (PAH) and 84 adult (AAH) patients and in 208 controls. In children, HLA-DRB1*1301 was the primary susceptibility allele (66.4% patients vs. 10.6% controls, relative risk [RR] = 16.3, Pc < 10-24) whereas HLA-DRB1*1302, which differs from HLA-DRB1*1301 by only 1 amino acid, appeared to be protective. The exclusion of individuals with HLA- DRB1*1301 from control and pediatric patients allowed us to find a secondary association of PAH with HLA-DRB1*0301. Possession of HLA-DRB1*1301, however, was associated with a lower therapeutic response rate. Analysis of peptide binding pocket residues indicated that Tyr 10, Ser 11, Ser 13, and Val 86 in the class II β chain were present in 85% of patients compared with 37% of controls, suggesting that a high proportion of AH susceptibility is attributable to these residues (etiologic fraction [EF] = 76%). In contrast to the class II associations in children, AAH was associated with HLA- DRB1*0405 (RR = 10.4, Pc < .005) but not with HLA-DRB1*1301 or HLA- DRB1*0301. In addition, HLA-DR4 with the class I gene, HLA-A11, appeared synergistic in predisposing AAH patients to develop extra-hepatic autoimmune (AI) manifestations (odds ratio [OR] = 104.9, Pc < 10-4). Concomitant differences in autoantibody profiles were also observed in PAH versus AAH: smooth muscle antibodies (SMA) were most prevalent in PAH but antinuclear antibodies were most prevalent in AAH (P = .003). This study therefore reveals that different HLA-DRB1 allotypes confer susceptibility to AH in children and adults and raises the possibility that PAH and AAH may be triggered by different factors.
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U2 - 10.1002/hep.510300611
DO - 10.1002/hep.510300611
M3 - Article
C2 - 10573514
AN - SCOPUS:0032722786
SN - 0270-9139
VL - 30
SP - 1374
EP - 1380
JO - Hepatology
JF - Hepatology
IS - 6
ER -