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

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

doi:10.1097/MPG.0000000000000245

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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	457-462
Number of pages	6
Journal	Journal of Pediatric Gastroenterology and Nutrition
Volume	58
Issue number	4
DOIs	https://doi.org/10.1097/MPG.0000000000000245
Publication status	Published - Apr 2014

Keywords

human study
autoimmunity
autoantibodies
hepatitis
humoral immunity
PRIMARY BILIARY-CIRRHOSIS
CHRONIC ACTIVE HEPATITIS
REGULATORY T-CELLS
ANTIBODIES
CHOLANGITIS
CHILDHOOD
GENOTYPE
CRITERIA
HISTORY
INSULIN

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/MPG.0000000000000245

Cite this

Wang, P., Su, H., Underhill, J., Blackmore, L. J., Longhi, M. S., Grammatikopoulos, T., Okokon, E. V., Davies, E. T., Vergani, D., Mieli-Vergani, G., & Ma, Y. (2014). Autoantibody and Human Leukocyte Antigen Profiles in Children With Autoimmune Liver Disease and Their First-Degree Relatives. Journal of Pediatric Gastroenterology and Nutrition, 58(4), 457-462. https://doi.org/10.1097/MPG.0000000000000245

@article{19c77699ee5f4ece8dbdc7a956261ec5,

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

abstract = "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.",

keywords = "human study, autoimmunity, autoantibodies, hepatitis, humoral immunity, PRIMARY BILIARY-CIRRHOSIS, CHRONIC ACTIVE HEPATITIS, REGULATORY T-CELLS, ANTIBODIES, CHOLANGITIS, CHILDHOOD, GENOTYPE, CRITERIA, HISTORY, INSULIN",

author = "Pengyun Wang and Haibin Su and James Underhill and Blackmore, {Laura J.} and Longhi, {Maria Serena} and Tassos Grammatikopoulos and Okokon, {Elizabeth Veronica} and Davies, {Edward T.} and Diego Vergani and Giorgina Mieli-Vergani and Yun Ma",

year = "2014",

month = apr,

doi = "10.1097/MPG.0000000000000245",

language = "English",

volume = "58",

pages = "457--462",

journal = "Journal of Pediatric Gastroenterology and Nutrition",

issn = "0277-2116",

publisher = "Lippincott Williams and Wilkins",

number = "4",

}

Wang, P, Su, H, Underhill, J, Blackmore, LJ , Longhi, MS , Grammatikopoulos, T, Okokon, EV, Davies, ET, Vergani, D , Mieli-Vergani, G & Ma, Y 2014, 'Autoantibody and Human Leukocyte Antigen Profiles in Children With Autoimmune Liver Disease and Their First-Degree Relatives', Journal of Pediatric Gastroenterology and Nutrition, vol. 58, no. 4, pp. 457-462. https://doi.org/10.1097/MPG.0000000000000245

TY - JOUR

T1 - Autoantibody and Human Leukocyte Antigen Profiles in Children With Autoimmune Liver Disease and Their First-Degree Relatives

AU - Wang, Pengyun

AU - Su, Haibin

AU - Underhill, James

AU - Blackmore, Laura J.

AU - Longhi, Maria Serena

AU - Grammatikopoulos, Tassos

AU - Okokon, Elizabeth Veronica

AU - Davies, Edward T.

AU - Vergani, Diego

AU - Mieli-Vergani, Giorgina

AU - Ma, Yun

PY - 2014/4

Y1 - 2014/4

N2 - 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.

AB - 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.

KW - human study

KW - autoimmunity

KW - autoantibodies

KW - hepatitis

KW - humoral immunity

KW - PRIMARY BILIARY-CIRRHOSIS

KW - CHRONIC ACTIVE HEPATITIS

KW - REGULATORY T-CELLS

KW - ANTIBODIES

KW - CHOLANGITIS

KW - CHILDHOOD

KW - GENOTYPE

KW - CRITERIA

KW - HISTORY

KW - INSULIN

U2 - 10.1097/MPG.0000000000000245

DO - 10.1097/MPG.0000000000000245

M3 - Article

SN - 0277-2116

VL - 58

SP - 457

EP - 462

JO - Journal of Pediatric Gastroenterology and Nutrition

JF - Journal of Pediatric Gastroenterology and Nutrition

IS - 4

ER -

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

Abstract

Keywords

UN SDGs

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