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Association of HLA-DR genes with mild idiopathic adulthood biliary ductopenia
M E García-Jiménez1, J A Quiroga, M L Gutiérrez
1Institute of Hepatology, Hospital Pardo de Aravaca, Madrid, Spain.
Objective:
Mild idiopathic adulthood ductopenia (MIAD) is an asymptomatic chronic cholestatic liver disease characterized by the loss of interlobular bile ducts in <50% of the portal tracts. Although the underlying cause of MIAD is unknown, the host factors may contribute to the patient's susceptibility to the disease. The aim of this work was to investigate the immunogenetics in the pathogenesis of MIAD.
Methods:
We prospectively studied 22 Caucasian patients with MIAD. Peripheral blood was collected, and HLA-DR typing was performed by polymerase chain reaction with sequence-specific primers followed by sequencing for subtyping. Results were compared with those from 140 age- and sex-matched controls.
Results:
There was no significant association between HLA-DRB1 alleles and the disease, although a trend was found in MIAD patients with the DRB1*1502 allele (five of 44 vs four of 280 in controls; p corrected = 0.055; chi2 = 13.9). Multiple HLA-DRB1 alleles (*04, *11, *15) showed increased frequencies in MIAD patients. Further subtyping revealed a motif (positions 25-32 of the beta1 chain) present in 17 (77.3%) patients, which was significantly associated with MIAD (p = 0.049; chi2 = 3.87). Seven patients (31.8%) and 21 (15%) controls coded for this motif in their two alleles (p = 0.068; chi2 = 3.76). Among MIAD patients, those seven had abnormal ALT levels (p = 0.017) and their gamma-glutamyltransferase and ALT values tended to be more increased.
Conclusions:
These results provide evidence of an immunogenetic basis of susceptibility to MIAD in Caucasian individuals.
Insights
Investigating immunogenetics in mild idiopathic adulthood ductopenia (MIAD) revealed a specific HLA-DRB1 beta1 chain motif associated with disease susceptibility in Caucasian individuals. This finding suggests a genetic component influencing MIAD pathogenesis.
Area of Science:
- Immunogenetics
- Hepatology
- Chronic Liver Disease
Background:
- Mild idiopathic adulthood ductopenia (MIAD) is a chronic cholestatic liver disease of unknown etiology.
- Host factors are suspected contributors to disease susceptibility.
- Understanding the immunogenetic basis may elucidate MIAD pathogenesis.
Purpose of the Study:
- To investigate the role of immunogenetics in the pathogenesis of MIAD.
- To identify potential host genetic factors predisposing individuals to MIAD.
Main Methods:
- Prospective study of 22 Caucasian MIAD patients and 140 controls.
- HLA-DRB1 typing using polymerase chain reaction with sequence-specific primers and sequencing.
- Analysis of HLA-DRB1 alleles and a specific beta1 chain motif.
Main Results:
- No significant association between specific HLA-DRB1 alleles and MIAD, though a trend for DRB1*1502 was observed.
- Increased frequencies of HLA-DRB1 alleles (*04, *11, *15) noted in MIAD patients.
- A specific beta1 chain motif (positions 25-32) was significantly associated with MIAD susceptibility (p=0.049).
- MIAD patients with the motif showed a trend towards elevated ALT and GGT levels.
Conclusions:
- The study provides evidence for an immunogenetic basis of susceptibility to MIAD in Caucasian individuals.
- A specific HLA-DRB1 beta1 chain motif may play a role in MIAD pathogenesis.