RGD Reference Report - Pediatric and adult forms of type I autoimmune hepatitis in Argentina: evidence for differential genetic predisposition. - Rat Genome Database

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Pediatric and adult forms of type I autoimmune hepatitis in Argentina: evidence for differential genetic predisposition.

Authors: Pando, M  Larriba, J  Fernandez, GC  Fainboim, H  Ciocca, M  Ramonet, M  Badia, I  Daruich, J  Findor, J  Tanno, H  Canero-Velasco, C  Fainboim, L 
Citation: Pando M, etal., Hepatology. 1999 Dec;30(6):1374-80.
RGD ID: 5147856
Pubmed: PMID:10573514   (View Abstract at PubMed)
DOI: DOI:10.1002/hep.510300611   (Journal Full-text)

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 beta 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
H2-Eb1Mouseautoimmune hepatitis susceptibilityISOHLA-DRB1 (Homo sapiens)DNA:polymorphisms: :multiple (human)RGD 
HLA-DRB1Humanautoimmune hepatitis susceptibilityIAGP DNA:polymorphisms: :multiple (human)RGD 
RT1-Db1Ratautoimmune hepatitis susceptibilityISOHLA-DRB1 (Homo sapiens)DNA:polymorphisms: :multiple (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
RT1-Db1  (RT1 class II, locus Db1)

Genes (Mus musculus)
H2-Eb1  (histocompatibility 2, class II antigen E beta)

Genes (Homo sapiens)
HLA-DRB1  (major histocompatibility complex, class II, DR beta 1)


Additional Information