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HLA associations with HBV carriage and proteinuria
Rajendra Bhimma1, Mahomed Coovadia, Mike G Hammond
1Department of Paediatrics and Child Health, Nelson R. Mandela School of Medicine, University of Natal, Private Bag 7, Congella, 4013, South Africa. bhimma@nu.ac.za
Insights
The human leucocyte antigen (HLA) DQB1*0603 gene does not appear to predispose individuals to hepatitis B virus (HBV) carriage or abnormal proteinuria in family members. Additional factors likely contribute to the development of HBV-associated membranous nephropathy (MN).
Area of Science:
- Immunogenetics
- Nephrology
- Virology
Background:
- Hepatitis B virus (HBV)-associated membranous nephropathy (MN) has known associations with human leucocyte antigen (HLA) genes.
- Previous research identified HLA DQB1*0603 as a potential risk factor in Black children with HBV-MN.
Purpose of the Study:
- To investigate whether the HLA DQB1*0603 allele increases susceptibility to HBV infection and the development of abnormal proteinuria.
- To examine the role of HLA DQB1*0603 in HBV carriage and proteinuria within families affected by HBV-MN.
Main Methods:
- Studied 70 family members of 14 children with HLA DQB1*0603-positive HBV-MN.
- Assessed HBV infection using ELISA, slot-blot hybridization, and PCR.
- Determined HLA antigen types via lymphocytotoxic tests and sequence-specific primers.
- Defined abnormal proteinuria by a protein/creatinine ratio ≥ 0.2.
- Analyzed associations using mean probability ratio (LOD scores).
Main Results:
- 47% of family members had HBV infection, and 27% exhibited abnormal proteinuria.
- No significant association was found between HLA DQB1*0603 and HBV carriage (LOD scores: anti-log sum = 2.0559, average = 0.23).
- No significant association was observed between HLA DQB1*0603 and abnormal proteinuria (LOD scores: anti-log sum = 3.8587, average = 0.43).
Conclusions:
- The HLA DQB1*0603 allele does not appear to be a significant predisposing factor for HBV carriage or abnormal proteinuria in family members of HBV-MN patients.
- The findings suggest that other genetic or environmental factors play a crucial role in the pathogenesis of HBV-associated MN.
- The severity of proteinuria, reflecting glomerular damage, may be the primary distinguishing feature associated with HLA DQB1*0603 in HBV-MN.
Abstract:
Human leucocyte antigen (HLA) associations have been reported in children with hepatitis B virus (HBV) associated membranous nephropathy (MN). In a previous study, we found an association with HLA DQB1*0603 in black children with HBVMN. To determine whether HLA DQB1*0603 predisposes to HBV carriage and development of abnormal proteinuria, we studied 70 family members of 14 children with HBVMN positive for HLA DQB1*0603. HBV was determined using third generation ELISA, slot-blot hybridisation, and nested polymerase chain reaction. HLA class I antigens were determined using a two-staged lymphocytotoxic test whereas class II antigen typing was done using sequence-specific primers. Abnormal proteinuria was defined by a protein/creatinine ratio > or =0.2. Associations of HLA DQB1*0603 with HBV carriage and abnormal proteinuria were determined using the mean probability ratio (LOD scores). Forty-seven (67%) family members were positive for HBV infection. Nineteen (27%) had abnormal range proteinuria. LOD scores in the study subjects with DQB1*0603 who were HBV negative versus those with DQB1*0603 who were HBV positive was not significant (anti-log sum =2.0559 and average 0.23). When a similar calculation was made for abnormal proteinuria, there were no significant findings (anti-log sum =3.8587 and average 0.43). This lack of association of HLA DQB1*0603 with either HBV carriage or abnormal proteinuria in family members suggests that additional factors may play a role in predisposing children to chronic HBV carriage and the development of MN. We therefore conclude that the main effect of HLA DQB1*0603 that distinguishes family members from HBVMN is the degree of proteinuria, which is a reflection of the severity of glomerular basement membrane damage in the latter.