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HLA class I and II in black children with hepatitis B virus-associated membranous nephropathy
Rajendra Bhimma1, Mike G Hammond, Hoosen M Coovadia
1Department of Paediatrics & Child Health, University of Natal, Nelson R. Mandela School of Medicine, Natal, South Africa. bhimma@nu.ac.za
Background:
The pathogenetic mechanisms by which individuals with chronic hepatitis B virus (HBV) infection develop membranous nephropathy (MN) are probably dependent on interactions between viral, host and environmental factors; some evidence suggests a genetic predisposition. HBVMN constitutes a major etiological group in black children with nephrotic syndrome. We therefore explored the HLA associations in black children with HBVMN.
Method:
Thirty black children, age range 2 to 16 years, with biopsy-proven HBVMN, were the subjects of the study. HBV status was determined using third generation ELISA. HLA A, B and C antigens were determined using a two-stage lymphocytotoxic test. HLA DRB1* and DQB1* typing was done using sequence-specific primers. HLA class 1 and II antigen frequencies of the study subjects were compared to controls that were randomly chosen healthy blood donors from the same population.
Results:
HLA DQB1*0603 was increased in patients with HBVMN compared to controls (chi2 = 13.65, RR = 4.3). DRB1*07 and DQB1*02 were increased in frequency in the study subjects but failed to reach statistical significance. There was no significant difference in the frequencies of class 1 antigens in the study group compared to controls.
Conclusion:
To our knowledge, this is the first report of HLA associations in black patients with HBVMN in whom Class 1 and 11 antigens were determined using molecular methodology. There was a high frequency of DQB1*0603 in subjects compared to controls, suggesting a possible genetic predisposition to the development of HBVMN.
Insights
Hepatitis B virus-associated membranous nephropathy (HBV-MN) in black children shows a genetic link. The study found a higher frequency of HLA DQB1*0603 in these patients, suggesting a predisposition to developing this kidney disease.
Area of Science:
- Immunogenetics
- Nephrology
- Virology
Background:
- Chronic Hepatitis B Virus (HBV) infection can lead to membranous nephropathy (MN), especially in black children with nephrotic syndrome.
- Genetic predisposition is suspected in the development of HBV-associated MN (HBVMN).
Purpose of the Study:
- To investigate Human Leukocyte Antigen (HLA) associations in black children diagnosed with HBVMN.
- To identify potential genetic factors contributing to HBVMN pathogenesis.
Main Methods:
- Studied 30 black children (ages 2-16) with biopsy-proven HBVMN.
- Determined HBV status via ELISA and HLA class I (A, B, C) and class II (DRB1*, DQB1*) antigens using lymphocytotoxic tests and sequence-specific primers.
- Compared HLA antigen frequencies with healthy blood donors from the same population.
Main Results:
- A statistically significant increase in HLA DQB1*0603 was observed in HBVMN patients compared to controls (RR=4.3).
- HLA DRB1*07 and DQB1*02 showed increased frequency but did not reach statistical significance.
- No significant differences in HLA class I antigen frequencies were found between patients and controls.
Conclusions:
- This study is the first to report HLA associations in black HBVMN patients using molecular methods.
- The high frequency of HLA DQB1*0603 suggests a potential genetic predisposition to HBVMN in this population.
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