HLA associations with HBV carriage and proteinuria.
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.
Bhimma
Rajendra
R
Department 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
Coovadia
Mahomed
M
Hammond
Mike G
MG
Kramvis
Anna
A
Adhikari
Miriam
M
Kew
Michael C
MC
D000293:Adolescent; D002353:Carrier State; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D015433:Glomerulonephritis, Membranous / Q000209:etiology / Q000235:genetics; D006683:HLA-DQ Antigens / Q000032:analysis / Q000502:physiology*; D059866:HLA-DQ beta-Chains; D006509:Hepatitis B / Q000209:etiology* / Q000235:genetics; D006801:Humans; D008297:Male; D011336:Probability; D011507:Proteinuria / Q000209:etiology* / Q000235:genetics
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen