Detection of double mutant X antigen/antibody in sera of patients with hepatitis B virus infection and its implication / 中华传染病杂志

ABSTRACT

Objective To explore the correlation between serum hepatitis B virus (HBV) X antigen/antibody (HBxAg-wild/HBxAb-wild,and HBxAg-mutant/HBxAb-mutant) and the disease progression in patients with chronic HBV infection.Methods A direct enzyme immunosorbent asssay (ELISA) was performed to detect HBxAb using recombinant antigen,and a double antibody sandwich ELISA assay to detect HBxAg using monoclonal antibody and specific rabbit polyclonal antibody.HBxAg-wild/HBxAb-wild and HBxAg-mutant/HBxAb-mutant were tested in sera from cases at different stages of chronic HBV infection.A chi-square test was employed to examine statistical significance.Results The positive rates of HBxAg-wild and HBxAg-mutant in the chronic asymptomatic HBV carriers,chronic hepatitis,hepatitis B-related cirrhosis and liver cancer were 6.2％ (2/32),10.7％ (3/28),28.6％ (6/21),43.6％ (17/39) and 3.1％ (1/32),10.7％ (3/28),33.3％ (7/21),48.7％ (19/39),respectively.The positive rates of HBxAb-wild and HBxAb-mutant in the above mentioned groups were 6.2％ (2/32),21.4％ (6/28),38.1％ (8/21),53.8％ (21/39)and 6.2％ (2/32),25.0％ (7/28),42.9％ (9/21),61.5％ (24/39) respectively.The positive rates of HBxAg-wild and HBxAg-mutant were not significantly different among the above groups (x2 =0.871,0.780,0.565 and 0.317,respectively; all P＞0.05) ; The positive rates of HBxAb-wild and HBxAb-mutant were also similar among all the groups (x2 =0.780,0.709,0.580 and 0.210,respectively; all P＞0.05).The positive rates of HBxAg-wild,HBxAb-wild,HBxAg-mutant,HBxAb-mutant in patients with low viral loads (HBV DNA＜1 × 104 copy/mL) were 36.5％ (23/63),44.4％ (28/63),42.9％ (27/63) and 54.0％ (34/63),respectively,those in patients with high viral loads (HBVDNA≥1×104 copy/mL) were 8.8％ (5/57),15.8％ (9/57),5.3％ (3/57) and 14.0％ (8/57),respectively.The positive rates of HBxAg and HBxAb were significantly higher in cases with low viral loads than those with high viral loads (x2 =12.869,11.522,22.556 and 20.976,respectively; all P＜0.05).The positive rates of HBxAg-wild,HBxAb-wild,HBxAg-mutant,HBxAb-mutant in the HBeAg positive group were 21.7％ (18/83),30.1％ (25/83),22.9％ (19/83) and 32.5％ (27/83),respectively,while those in the HBeAg negative group were 27.0％ (10/37),32.4％ (12/37),29.7％ (11/37) and 40.5％ (15/37),respectively.No significant difference of HBxAg/HBxAb positive rates between HBeAg positive group and HBeAg negative group was noticed (x2 =0.408,0.064,0.638 and 0.722,respectively; all P＞0.05).Conclusions The antigenicity and specificity of HBV X protein remains similar after the occurrence of A1762T/G1764A double mutant in X gene.It is also found that the positive rates of HBxAg and HBxAb increase with disease progression.HBxAg/HBxAb might be promoting factors for tumorigenesis in chronic HBV infection.HBxAg and HBxAb might have negative influence on HBV replication.