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HLA-DRB and -DQB1 alleles in Polish patients with hepatitis B associated membranous nephropathy
R W Vaughan1, A Zurowska, G Moszkowska
1South Thames Tissue Typing, Guy's Hospital, London, UK.
Insights
Hepatitis B-associated membranous nephropathy (HBVMN) in children shows a significant association with the DQB1*0303 human leukocyte antigen (HLA) allele. This finding suggests a genetic predisposition in pediatric HBVMN patients from Northern Poland.
Area of Science:
- Immunogenetics
- Nephrology
- Hepatology
Background:
- Membranous nephropathy associated with hepatitis B infection (HBVMN) is a significant renal complication.
- Previous studies in Caucasoids linked idiopathic membranous nephropathy and poor hepatitis B vaccine response to HLA-DR3.
- Understanding genetic factors in pediatric HBVMN is crucial for disease management and prevention.
Purpose of the Study:
- To investigate the association of HLA-DRB and -DQB1 alleles with pediatric HBVMN in a Northern Polish cohort.
- To test the hypothesis that HLA-DR3 is more frequent in HBVMN patients compared to controls.
Main Methods:
- Human leukocyte antigen (HLA) typing of DRB and DQB1 alleles was performed using polymerase chain reaction with sequence-specific primers (PCR-SSP).
- Study included 42 pediatric HBVMN patients, 55 healthy children, and 40 chronic hepatitis B patients without renal disease.
- Allele frequencies were compared between patient and control groups, with statistical analysis including correction for multiple comparisons.
Main Results:
- No significant increase in HLA-DRB1*0301 frequency was observed in HBVMN patients compared to healthy controls.
- A statistically significant increase in HLA-DQB1*0303 frequency was found in HBVMN patients versus healthy controls (Pc=0.02).
- The frequency of HLA-DQB1*0303 was also higher in HBVMN patients compared to hepatitis B controls, though significance varied with statistical correction.
Conclusions:
- The HLA-DQB1*0303 allele is significantly associated with pediatric membranous nephropathy in hepatitis B virus infection.
- The study did not find a significant association with HLA-DRB1*0301, contrary to the initial hypothesis based on other populations.
- These findings highlight a specific genetic susceptibility marker for HBVMN in the studied pediatric population.
Abstract:
We have studied the HLA-DRB and -DQB1 alleles of 42 paediatric patients who have suffered from membranous nephropathy associated with a hepatitis B infection (HBVMN). These patients were all from the Gdansk area of Northern Poland and the disease was diagnosed by light and electron microscopy. The control population consisted of 55 healthy children, approximately age matched, from schools in Gdansk. In addition we have also analysed 40 patients chronically infected with hepatitis B, without any renal involvement, as hepatitis B disease controls. The HLA alleles were defined using PCR/SSP. As idiopathic membranous nephropathy and low responsiveness to hepatitis B vaccine have been found to be associated with DR3 in Caucasoids, our hypothesis was that the HBVMN patients would show an increase in DR3. Our results indicate that, although there is a small increase in the frequency of DRBl*0301 in the HBVMN patients (16/42 38%) when compared to the healthy controls (15/55 31%), this does not approach significance. There is a significant increase in the frequency of DQB1*0303 in the HBVMN patients vs the healthy controls, after correction for the number of antigens detected (Pc)(13/42 vs 2/55, RR=11.6, P=0.0007, Pc=0.02). A similar increase in DQB1*0303 is seen in the HBVMN patients when compared to the hepatitis controls (13/42 vs 4/40) but this is only significant before correction (RR=4.3, P=0.04).
