Distinct Clinical Patterns Associated with HLA-DRB1 Genotypes in Pediatric Autoimmune Liver Diseases
- 12nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
- 22nd Pediatric Clinic, Center of Expertise in Pediatric Liver Rare Diseases, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
Abstract
Autoimmune liver diseases (AILD), including autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC), are rare but important causes of chronic liver disease in children. Although HLA-DRB1 alleles have been associated with disease susceptibility, their role in modulating the clinical phenotype and long-term outcome of pediatric AILDs remains incompletely understood. We aimed to characterize the distribution of HLA-DRB1 alleles and genotype combinations and describe the accompanying clinical features in a pediatric AILD cohort. Thirty children diagnosed with AIH-1 (n = 14), AIH-2 (n = 6), or ASC (n = 10) underwent HLA-DRB1 genotyping. Clinical presentation, fibrosis stage, treatment response, and associated autoimmune diseases were retrospectively analyzed. The most frequent alleles copies were HLA-DRB1*03 (n = 15), predominantly identified in AIH, and HLA-DRB1*13 (n = 14), identified in both AIH and ASC. Genotype combinations involving these alleles were observed across a broad spectrum of clinical presentations, fibrosis stages, treatment responses, and extrahepatic autoimmune manifestations. In this small cohort, HLA-DRB1*14-containing genotypes were observed in several patients with severe disease features, including advanced fibrosis, cirrhosis, treatment-refractory disease, and ulcerative colitis. Patients carrying HLA-DRB1*11, HLA-DRB1*15, or HLA-DRB1*16 had favorable hepatic outcomes despite severe initial presentation or associated extrahepatic autoimmune manifestations; however, the number of carriers was small. Clinical features varied among patients carrying different genotype combinations; however, the independent contribution of the accompanying allele could not be assessed. Our findings illustrate marked clinical heterogeneity among children carrying different HLA-DRB1 alleles and genotype combinations. In this exploratory cohort, selected HLA-DRB1 combinations co-occurred with distinct clinical patterns. HLA profiling may have a role in future risk stratification and individualized follow-up of children with AILD, but these observations are hypothesis-generating, they do not support genotype-based clinical management and require validation in larger, multicenter cohorts.
Related
- OP–133 Not all mutations are equal: distinct clinical manifestations across fmf genotypes in azerbaijani pediatric patients
- Possible Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS) Presenting in Late Adolescence and Early Adulthood: A Case Series.
- Three distinct trajectories of early oral feeding ability in preterm infants and their associated clinical factors
- Clinical characteristics and exploratory factors associated with in-hospital mortality in pediatric severe viral encephalitis
- Acneiform eruption associated with Janus kinase inhibitors in pediatric inflammatory bowel disease: Case series and clinical management guidance
BibTeX
@article{grama2026distinct,
title = {{Distinct Clinical Patterns Associated with HLA-DRB1 Genotypes in Pediatric Autoimmune Liver Diseases}},
author = {Alina Grama and Alexandra Mititelu and Gabriel Benţa and Raisa Sucaciu and Daniel Popescu and Bianca Mariş and Alexia Onaciu and Ştefan Agoston and Tudor Lucian Pop},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209002},
url = {https://www.mdpi.com/1422-0067/27/20/9002},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Distinct Clinical Patterns Associated with HLA-DRB1 Genotypes in Pediatric Autoimmune Liver Diseases
AU - Alina Grama
AU - Alexandra Mititelu
AU - Gabriel Benţa
AU - Raisa Sucaciu
AU - Daniel Popescu
AU - Bianca Mariş
AU - Alexia Onaciu
AU - Ştefan Agoston
AU - Tudor Lucian Pop
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209002
UR - https://www.mdpi.com/1422-0067/27/20/9002
AB - Autoimmune liver diseases (AILD), including autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC), are rare but important causes of chronic liver disease in children. Although HLA-DRB1 alleles have been associated with disease susceptibility, their role in modulating the clinical phenotype and long-term outcome of pediatric AILDs remains incompletely understood. We aimed to characterize the distribution of HLA-DRB1 alleles and genotype combinations and describe the accompanying clinical features in a pediatric AILD cohort. Thirty children diagnosed with AIH-1 (n = 14), AIH-2 (n = 6), or ASC (n = 10) underwent HLA-DRB1 genotyping. Clinical presentation, fibrosis stage, treatment response, and associated autoimmune diseases were retrospectively analyzed. The most frequent alleles copies were HLA-DRB1*03 (n = 15), predominantly identified in AIH, and HLA-DRB1*13 (n = 14), identified in both AIH and ASC. Genotype combinations involving these alleles were observed across a broad spectrum of clinical presentations, fibrosis stages, treatment responses, and extrahepatic autoimmune manifestations. In this small cohort, HLA-DRB1*14-containing genotypes were observed in several patients with severe disease features, including advanced fibrosis, cirrhosis, treatment-refractory disease, and ulcerative colitis. Patients carrying HLA-DRB1*11, HLA-DRB1*15, or HLA-DRB1*16 had favorable hepatic outcomes despite severe initial presentation or associated extrahepatic autoimmune manifestations; however, the number of carriers was small. Clinical features varied among patients carrying different genotype combinations; however, the independent contribution of the accompanying allele could not be assessed. Our findings illustrate marked clinical heterogeneity among children carrying different HLA-DRB1 alleles and genotype combinations. In this exploratory cohort, selected HLA-DRB1 combinations co-occurred with distinct clinical patterns. HLA profiling may have a role in future risk stratification and individualized follow-up of children with AILD, but these observations are hypothesis-generating, they do not support genotype-based clinical management and require validation in larger, multicenter cohorts.
SN - 1422-0067
ER -