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Autoantibody and Human Leukocyte Antigen Profiles in Children With Autoimmune Liver Disease and Their First-Degree Relatives

Wang, Pengyun*; Su, Haibin||; Underhill, James*; Blackmore, Laura J.*; Longhi, Maria Serena*; Grammatikopoulos, Tassos; Okokon, Elizabeth Veronica; Davies, Edward T.§; Vergani, Diego*; Mieli-Vergani, Giorgina; Ma, Yun*

Journal of Pediatric Gastroenterology and Nutrition: April 2014 - Volume 58 - Issue 4 - p 457–462
doi: 10.1097/MPG.0000000000000245
Original Articles: Hepatology and Nutrition

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.

Address correspondence and reprint requests to Dr Yun Ma, Institute of Liver Studies, King's College Hospital, Denmark Hill, London SE5 9RS, UK (e-mail:

Received 9 November, 2013

Accepted 9 November, 2013

P.W. and H.S. share first authorship. D.V., G.M.V., and Y.M. participated equally in this study.

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P.W. was supported by the PhD studentship from the Medical Research Council (MRC), UK; H.S. was supported by a scholarship from Beijing 302 Hospital, China; L.J.B. was supported by the King's College Hospital Foundation Trust and is presently supported by the Clinical Training Fellowship from the Wellcome Trust, UK; M.S.L. was supported by the Roger Dobson Fund, King's College Hospital Charity, UK, when this project was started and is presently supported by the Clinician Scientist Fellowship from MRC.

The authors report no conflicts of interest.

© 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,