Study On The Expression Level Of Interferon And Its Receptor In Renal Tissues Of Patients With Hepatitis B Virus-Associated Glomerulonephritis

Background:A variety of extrahepatic disorders,one of the commonest being hepati- tis B virus-associated glomerulonephritis(HBV-GN),may appear in persons chronic- ally infected with hepatitis B virus(HBV).The incidence of HBV-GN is higher in China where HBV infection is endemic,in particular,that of in children.The patho- genic mechanisms by which individuals with chronic HBV infection develop nephr- opathy are not clearly defined.It is difficult for patients with HBV-GN to get an effective therapy.The antiviral therapy is one of the main therapy means.The effectiveness of interferon(IFN)-αtherapy in different patients with HBV-GN is the discrepancy.It is important for investigators to deeply explore pathogenic mechanisms of HBV-GN and a factor which might be useful for predicting the response to IFN therapy.The expression level of interferon-γ, interferon-γreceptor (IFN-γR)and interferon-α/βreceptor (IFN-α/βR)in renal tissues were detected by using immu- nohistochemistry. What IFN-γplayed role in the onset and deveplopment of HBV-GN were studied.It was investigated that the relationship between IFN-α/βR expression level in renal tissues and response to IFN therapy in patient with HBV-GN.Part one The relationship between interferon-α/βreceptor expression level in renal tissues and response to interferon-α2b therapy of patients with HBV-GN Objective:The level of interferon-α/βreceptor expression were determined in pre- treatment renal tissues of HBV-GN patients with interferon-α2b.The relationship be- tween expression level of IFN-α/βreceptor and response to interferon-α2b therapy were investigated.Factors which might be useful for predicting the response to IFN therapy were studied for reducing economic burden to non-responder.Methods:50 patients with HBV-GN were given recombinant human interferon -α2b at a dose of 3 MU by intramuscular injection on alternative days for 24 weeks.In addition, 39 patients who were nephrotic syndrome in clinical manifestation were added to prednisone.HBV-GN patients were divided into three groups based on resp- onse to interferon therapy.There were 10 patients who were in interferon completely responsive group,25 patients in partially responsive group and 15 patients were non-responder. The level of interferon-α/βreceptor expression were determined immunohistochemically in pre-treatment renal tissues of 50 HBV-GN patients who were given interferon-α2b.The relationship between expression level of IFN-α/βreceptor and response to interferon-α2b therapy were analyzed.Results:(1)The expression level of renal(glomeruli and renal tubules)IFN-α/βrece- ptor in membranous nephropathy group(MN)(2.64±0.51,5.35±0.58) and in mesangial proliferative glomerulonephritis group(MsPGN)(2.47±0.38,5.05±0.45) was significa- ntly higher (P<0.05) than that of in membrane proliferative glomerulonephritis group (MPGN) (1.17±0.28,3.02±0.38),but there was no statistical significance (P>0.05) in MN group compared to MsPGN group.(2) The expression level of renal IFN-α/βreceptor in simple type nephrotic syndrome group(2.80±0.45,5.97±0.36) and in hematuria and/or albuminuria group(2.56±0.45,5.73±0.49) was significantly higher (P<0.05) than that of in nephritic type nephrotic syndrome group(1.34±0.70,3.24±0.55).Hematuria and/or albuminuria group had not significantly higher renal IFN -α/βreceptor expression compared to simple type nephrotic syndrome group (P>0.05).(3) The expression level of renal IFN-α/βreceptor in interferon responsive group was significantly higher (P<0.05) than that of in interferon non-responsive group.Completely responsive group had not significantly higher renal IFN-α/βrece- ptor expression compared to partially responsive group (P>0.05).(4)Completely responsive group had significantly higher renal IFN-α/βreceptor expression ,higher level of serum albumin and C3,lower concentration of 24h-urine protein excretion and lower level of serum HBV-DNA compared to non-responsive group (P<0.05).The relationship between the five factors aboved and response to interferon was analyzed by using Logistic regression analysis.It was suggested that the expression level of renal IFN-α/βclosely correlated with response to IFN therapy.Conclusions: The expression level of IFN-α/βin pre-treatment renal tissues might be useful for predicting the response to IFN therapy.Part two Expression of interferon-γand its receptor in renal tissues of patients with HBV-GNObjective:The expression level of IFN-γand IFN-γR in renal tissues were detected and the role of IFN-γin the onset and deveplopment of HBV-GN were studied.Methods:HBV-GN(experiment group)and non-HBV-GN(control group) were deter- mined by the detection of HBV-DNA in renal tissues by using in situ hybri- dization.The level of IFN-γand IFN-γR in renal tissues of 21 patients with HBV-GN and 20 patients with non-HBV-GN were examined immunohistochemically.Results:(1) Experiment group had significantly higher IFN-γ(2.46±1.08,4.31±1.60, P<0.05) and IFN-γR(2.03±0.93,3.53±1.74, P<0.05) expression in the glomeruli and renal tubules compared to control group [(1.62±1.15,2.94±1.25) (1.17±0.92,2.20±1.52)].(2) There was positive correlation between the level of IFN-γand IFN-γR expression in HBV-GN groups and the concentration of 24h-urine protein excretion, urine HBV-DNA and serum HBV-DNA,but there was negative correlation between that of IFN-γand IFN-γR expression and the level of serum C3.(3)The expression level of IFN-γin glomeruli and renal tubules closely correlated with that of IFN-γR(r =0.848, p=0.000 in glomerulus; r =0.829, p=0.000 in renal tubules).Conclusions: There was positive correlation between the level of IFN-γand IFN-γR expression in HBV-GN group and the concentration of 24h-urine protein excretion, urine HBV-DNA and serum HBV-DNA,but there was negative correlation between that of IFN-γand IFN-γR expression and the level of serum C3.It was suggested that IFN-γbinding to IFN-γR had been implicated in the onset and development of HBV-GN.