Autoantibody and human leukocyte antigen profiles in children with autoimmune liver disease and their first-degree relatives.
OBJECTIVE
Familial clustering of juvenile autoimmune liver disease (AILD), including autoimmune hepatitis and autoimmune sclerosing cholangitis (ASC), is rare, despite a high prevalence of autoimmune disorders in AILD families.


METHODS
To investigate this discrepancy, we measured autoantibodies diagnostic for AILD, anti-nuclear, anti-smooth muscle, anti-liver kidney microsomal type 1, anti-liver cytosol type 1, and anti-soluble liver antigen antibodies, and human leukocyte antigen profiles in 31 patients and 65 of their first-degree relatives (FDR). The autoantibody profile was compared with that of 42 healthy subjects (HS).


RESULTS
Autoantibodies were detected in 71% (22/31) patients. Anti-nuclear antibody or anti-smooth muscle antibody were present in 4/65 FDR (6.2%). HS were negative for all autoantibodies. The frequencies of homozygous HLA DRB1*0301 (DR3) genes and haplotype A1-B8-DR3 were higher in the patients (25% and 43%) than in FDR (9% and 27%) and HS (0% and 16%). The frequencies of disease-protective genes DR4 and/or DR15 were lower in the patients (25%) than in FDR (42%) and HS (42%). Only 1 family contained 2 patients with AILD, 1 with ASC and 1 with primary sclerosing cholangitis. Both patients possessed A1-B8-DR3 genes, the ASC being homozygous and the primary sclerosing cholangitis heterozygous. Six FDR had nonhepatic autoimmune disorders, none being autoantibody positive.


CONCLUSIONS
Homozygosity for DR3 plays a major role in the predisposition to juvenile AILD. Diagnostic autoantibodies for AILD are rare among patients' FDR and not linked to clinical manifestation of AILD.
*Institute of Liver Studies †Paediatric Liver, GI & Nutrition Centre ‡Clinical Biochemistry §Clinical Immunology, King's College London School of Medicine at King's College Hospital, Denmark Hill, London, UK ||Department of Transplantation, Beijing 302 Hospital, Xisihuanzhonglu, Beijing, China.
Pengyun
P
Wang
Haibin
H
Su
James
J
Underhill
Laura J
LJ
Blackmore
Maria Serena
MS
Longhi
Tassos
T
Grammatikopoulos
Elizabeth Veronica
EV
Okokon
Edward T
ET
Davies
Diego
D
Vergani
Giorgina
G
Mieli-Vergani
Yun
Y
Ma
D000293:Adolescent; D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015209:Cholangitis, Sclerosing / Q000235:genetics* / Q000276:immunology*; D005190:Family; D005260:Female; D006680:HLA Antigens / Q000097:blood*; D015788:HLA-A1 Antigen / Q000097:blood / Q000235:genetics; D015795:HLA-B8 Antigen / Q000097:blood / Q000235:genetics; D059810:HLA-DR Serological Subtypes / Q000097:blood; D015803:HLA-DR3 Antigen / Q000097:blood / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000097:blood; D059811:HLA-DRB1 Chains / Q000097:blood / Q000235:genetics; D006239:Haplotypes; D019693:Hepatitis, Autoimmune / Q000235:genetics* / Q000276:immunology*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000276:immunology; D010375:Pedigree; D055815:Young Adult
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; D006680:HLA Antigens; D015788:HLA-A1 Antigen; D015795:HLA-B8 Antigen; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; C094307:anti-liver cytosolic protein 1; C060729:anti-liver kidney microsome antibody; C046431:liver antigen LA-1