Expression of AIM2 is high and correlated with inflammation in hepatitis B virus associated glomerulonephritis

Abstract

Background & aimsInnate immunity is the first line of defense against invasive microbial infection, and AIM2 plays an important role in this process by sensing double-stranded DNA viruses. However, the role of AIM2 in regulating the immune response to viruses in vivo, especially in sensing hepatitis B virus (HBV), has not been examined. We hypothesized that the expression of AIM2 increases corresponding to HBV-mediated inflammation in patients with hepatitis B virus associated glomerulonephritis (HBV-GN), a condition which activates inflammatory mechanisms and causes renal damage. To test this hypothesis, we analyzed the expression of AIM2 in HBV-GN patients in relation to the inflammatory response to HBV infection.MethodsA total of 79 patients diagnosed with chronic nephritis (CN) were enrolled in this study, including 54 HBV-GN patients as the experimental group and 24 chronic glomerulonephritis (CGN) patients as the negative control group. Six patients diagnosed with chronic hepatitis B (CHB) were also enrolled as positive controls. Each CN patient received renal biopsy, and immunohistochemistry was used to detect the expression of AIM2 and inflammatory factors caspase-1 and IL-1β in the biopsy specimens. CHB patients received liver puncture biopsy, and immunohistochemistry was used to detect the expression of AIM2 in these specimens. Expression of AIM 2 among different groups and in relation to inflammatory factors caspase-1 and IL-1β was analyzed.ResultsThe expression of AIM2 in HBV-GN patients (81.4%) was significantly higher than in CGN patients (4.0%). Among the HBV-GN patients, expression of AIM2 was significantly higher in the high HBV replication group than in the low HBV replication group. AIM2 expression was not correlated with age, gender, HBeAg status in serum, HBV-antigen type deposited in renal tissue or pathological type of HBV-GN. However, AIM2 levels were positively correlated with the expression of caspase-1 and IL-1β in HBV-GN patients. The data suggest that AIM2 expression is directly correlated with HBV infection-associated inflammation.ConclusionThe elevation of AIM2 during HBV infection or replication may contribute to its associated inflammatory damage, thus providing a putative therapeutic target and a new avenue for researching the pathogenesis of HBV-GN.

Nationwide cohort study suggests that nucleos(t)ide analogue therapy decreases dialysis risk in Taiwanese chronic kidney disease patients acquiring hepatitis B virus infection

“…The same study also showed that patients with higher levels of serum HBV-DNA had lower level of serum complement, suggesting a correlation between serum HBV-DNA levels and the deposition of immune complexes, and the existence of a mechanism involving HBV-related immune complexes formed by passive trapping or in situ formation. Du et al[ 35 ] demonstrated that high levels of serum HBV-DNA correlated with the expression of inflammatory factors in renal biopsy specimens from HBV-GN patients. Deposition of immune complexes in the kidney is perceived to play a pivotal role in the pathogenesis of HBV-related nephropathy.…”

Inflammasome control of viral infection

“…Expression of AIM2, IL-1β and IL-18 in hepatitis B virus (HBV) infected human PBMCs correlates with viral load, and AIM2 expression is lower in chronic as compared to acute cases [26]. AIM2 expression also correlates with renal damage during HBV infection, possibly indicating that AIM2 enhances immunopathology during HBV infection [27,28], but a definitive role remains to be determined.…”

HBV/HCV Infection and Inflammation

“…The expression levels of absent in melanoma 2 (AIM2), during HBV infection or replication, have been found to be elevated. This generates inflammatory state and contributes to renal damage [135]. Also, TLR3-signalling has been implicated in HCV-related glomerular disease [136].…”