The Role Of Absent In Melanoma (AIM2) In The Pathgenesis Of Hepatitis B Virus Associated Glomerulonephritis

Background/AimsHepatitis B virus associated glomerulonephritis is the most extrahepatic manifestations of HBV infection. However, the pathogenesis of HBV-GN is still not clear. Most researches show that the pathogenesis of HBV-GN is immune injury.A recent study showed that AIM2is a cytoplasmic double-stranded DNA sensor. It could be activated by recognizing cytoplasmic double-stranded DNA and coming into being a immune complex, which triggers IL-1β maturation and secretion through Caspase-1and induces innate immune response. Then AIM2plays an important role in against infection with microbial or viral pathogens in human body. The aims of this study are to explore the role of activation and expression of AIM2in pathogenesis of Hepatitis B virus associated glomerulonephritis.MethodsFifty-four patients with Hepatitis B virus associated glomerulonephritis (HBV-GN) were recruited into the study group, twenty-five patients with Chronic glomerulonephritis (CGN) and six patients with Chronic hepatitis B (CHB) were included as negative control group and positive control group respectively. The diagnosis of HBV-GN was reference to the diagnosis criteria suggested by Beijing forum in1989. Immunohistochemistry was used to detect HBsAg, HBcAg expression in the kidney tissues of all cases. The diagnosis of chronic glomerulonephritis was reference to the diagnosis criteria of chronic kidney disease clinical guide suggested by American kidney fund in2002. The diagnosis of chronic hepatitis B was reference to the diagnosis criteria suggested by the Chinese liver disease association and Chinese Medical Association infectious disease society in2010. All patients were without immune inhibitors and antiviral treatment before biopsy, and associated with other hepatitis virus infection and other factors caused by secondary glomerulonephritis were excluded.Immunohistochemistry was used to detect the expression of AIM2、Caspase-1and IL-1β from both the study group and the negative control group in kidney tissues, and liver tissues from positive control group. The different expression of AIM2in each groups and relevance among AIM2, Caspase-1and IL-1β in Hepatitis B virus associated glomerulonephritis were analyzed by SPSS17.0software.Results1. The location of AIM2, Capase-1and IL-1β mainly concentrate in the cytoplasm of endothelial cells,intercapillary cells in the kidney tissues, and cytoplasm of liver cells in the liver tissues.2. The positive rates of AIM2in the study group and the negative control group were81.4%and4.0%respectively (x2=38.746,P<0.01).6CHB patients in positive control group all have the expression of AIM2.3. In study group,38patients showed Caspase-1positive expression among the44AIM2positive patients, however only3patients showed Caspase-1positive expression among the10AIM2negative patients. The difference has statistical significance (x2=11.246,P<0.01). Caspase-1and AIM2were positively correlated (rs=0.444,P<0.01).IL=1β and Caspase-1were positively correlated(rs=0.515,P<0.01), and IL-1β and AIM2were positively correlated (rs=0.379, P<0.01).4. In the study group, the expression of AIM2in patients with HBVDNA≥1×105copies/ml is significantly higher than that in those with HBVDNA<1×105 copies/ml (x2=6.097, P<0.05)5.In the study group, the differences of AIM2among different groups of gender, age and e antigen state have no statistical significance (x2=0.131,2.598,0.975,P>0.05).Conclusions1. The location of AIM2mainly concentrates in the cytoplasm of endothelial cells, intercapillary cells and liver cells.2. AIM2could recognize HBV-DNA and be activated, through Caspase-1activate innate immune system, then release inflammatory factor IL-1β, result in Hepatitis B virus associated glomerulonephritis.3. The express strength of AIM2is related to the duplication of HBV-DNA.