An Alteration In The Expression Fcγ Receptor In Immune Status Of HBV Infected

Background and aims:The mechanism of various clinical states of chronic hepatitis B virus(HBV) infection has been widely a concerned topic.In general,theindividual differences of the host immunity determined by gene play acrucial role in the clinical outcome of chronic HBV infection.Our projectused hepatitis B virus-infected human PBMC, and then use microarray toanalyse the whole genome. We found HBV patients had significantdifferences in Fc gamma receptor expression in different experimentalgroups as well as healthy controls. Fc gamma receptor is a very importantimmune cell surface molecules, playing a very important role in thebody’s immune system.Fc gamma receptor has activating and inhibitingtype; the activating type includes Fc gamma receptor Ia or Ib, IIa,IIIa/IIIb whereas Fc gamma R IIb is the only inhibitory receptors. Fcgamma receptor expression can be used as a marker to distinguish chronichepatitis B immune tolerant and clearance group, but there is no relevantreport to date.The purpose of this paper is to explore Fc gamma receptorexpression changes in different HBV immune status compared to healthycontrols, validating the HBV infection after the results of genome-wideexpression profile chip.And Fc gamma receptor expression differences inchronic hepatitis B, explore the value of in hepatitis B tolerant andclearance patients.Methods:64HBV patients（hepatitis B infection successfully cleared group12 patients、hepatitis B clearance group32patients、 hepatitis B toleratedgroup12patients）and14healthy controls were enrolled in this study.FcγRs mRNA expression on monocytes were quantified by real-timereverse-transcription polymerase chain reaction (real-time RT-PCR). Andthen we analyzed the correlation between mRNA expression of FcγRsand serum AST, ALT, HBsAg quantitation, HBV DNA levels in chronichepatitis B clearance and tolerated patients, respectively.Results:1、（1）Fc gamma receptor Ia expression in HBV infected patients:healthy controls1.01±0.19, hepatitis B tolerated group0.78±0.12,hepatitis B infection successfully cleared group0.12±0.06, hepatitis Bclearance group3.71±1.03.①Fc gamma receptor Ia expression inhepatitis B tolerated group is higher than hepatitis B infectionsuccessfully cleared group by0.66±0.06, which was statisticallysignificant(P=0.01).②The expression of Fc gamma receptor Ia inhepatitis B clearance group was higher than hepatitis B tolerated group by2.93±0.91, which was statistically significant (P=0.002).③Theexpression of the receptor in healthy controls was higher than hepatitis Binfection successfully cleared group by0.89±0.13，the difference wasstatistically significant (P=0.009).④In hepatitis B clearance patientsthan healthy controls higher2.70±0.84, the difference was statisticallysignificant (P=0.0097).⑤In hepatitis B clearance group the receptorexpression was higher compared to hepatitis B infection successfullycleared group by3.59±0.07, the difference was statistically significant(P=0.0027）.(2) Fc gamma receptor Ib expression in HBV infected patients:healthy controls1.00±0.75, hepatitis B infection tolerated group 0.93±0.14, successfully cleared hepatitis B infection group4.11±1.75,hepatitis B clearance group1.83±0.47.①In succesfully cleared hepatitisB infection group the Fc gamma receptor Ib expression was higher thanhepatitis B infection tolerated group by3.18±0.61，which was statisticallysignificant (P=0.0478）.②In successfully hepatitis B infection clearancegroup the expression was higher by3.11±1.00compared to healthycontrols, which was statistically significant (P=0.05）.（3）Fc gamma receptor IIa expression in HBV infected patients:healthy controls0.95±0.37, hepatitis B infection toleratedgroup1.04±0.41, successful hepatitis B infection clearance group1.57±0.69, hepatitis B clearance group2.80±0.58.①The expression ofIIa in hepatitis B infection clearance group was higher than hepatitis Binfection tolerated group by1.74±0.17, which was statistically significant(P=0.05).②In hepatitis B clearance group the expression was higher by1.85±0.21than healthy controls,the difference was statistically significant(P=0.042).（4）Fc gamma receptor IIb expression in HBV infected patients:healthy controls1.01±0.28, hepatitis B infection tolerated group3.72±1.21, hepatitis B infection successful clearance group0.53±0.14,hepatitis B clearance group1.06±0.19.①In hepatitis B infection toleratedgroup the above receptor expression was higher than hepatitis B infectionsuccessful clearance group by3.19±1.07, the difference wasstatisticant(P=0.0016).②In hepatitis B infection tolerated group thereceptor expression was higher than normal controls by2.71±0.93,thedifference was statisticant(P=0.0093).③The expression of the receptorin hepatitis B infection tolerated group was higher than hepatitis B clearance group by2.66±1.02,the difference was statisticant（P=0.0031）。(5) Fc gamma receptor IIIa expression in HBV patients:healthycontrols1.07±0.22, hepatitis B patients tolerated group3.41±0.80,hepatitis B infection successful clearance group1.93±0.49, hepatitis Bclearance group3.41±0.80.①The expression of IIIa in hepatitis Binfection clearance group was higher than hepatitis B infection toleratedgroup by2.55±0.62,which was statistically significant(P=0.0128).②Inhepatitis B clearance group the expression was higher by2.34±0.58thanhealthy controls,the difference was statistically significant (P=0.036).（6） Fc gamma receptor IIIb expression in HBV patients: healthycontrols1.04±0.12, hepatitis B patients tolerated group0.78±0.17,hepatitis B infection successfully cleared group1.48±0.27, hepatitis Bclearance group3.34±0.54.①The expression of IIa in hepatitis Binfection clearance group was higher than hepatitis B infection toleratedgroup by2.56±0.37, which was statistically significant（P=0.0002）。②In hepatitis B clearance group the receptor expression was highercompared to hepatitis B infection successfully cleared group by1.86±0.27, the difference was statistically significant（P=0.0127).③Theexpression of the receptor in hepatitis B clearance group was higher thanheathly controls by2.30±0.42，the difference was statistically significant(P=0.0015).④In succesfully cleared hepatitis B infection group the Fcgamma receptor IIIb expression was higher than hepatitis B infectiontolerated group by0.30±0.00， which was statistically significant(P=0.0186).2、Activating receptors(FcγR Ia、FcγR IIa) was positively correlatedwith ALT in hepatitis B clearance group and hepatitis B infection tolerated group(r=0.52,P=0.02and r=0.52， P=0.002). Activatingreceptors(FcγR Ia、FcγR IIa) was also positively correlated with AST inhepatitis B infection clearance group and hepatitis B infection toleratedgroup(r=0.36,P=0.04and r=0.43，P=0.009). Inhibitory FcγR IIb wasnegatively correlated with ALT、 AST （r=-0.50,P=0.003andr=-0.53,P=0.005).Conclusions:1、 Compared between hepatitis B infection tolerated group andhealthy controls, activated Fcγ receptor expression were significantlyhigher in hepatitis B infection clearance group。However, inhibitory Fcγreceptor expression was highest in hepatitis B infection tolerated group.The results above indicate that there is a remarkable enhancement ofFcγRs in different groups of HBV infection compared to healthy controls.2、Activated receptors(FcγR Ia、FcγR IIa)was positively correlatedwith ALT、AST levels in hepatitis B clearance and tolerated group,however, inhibitory receptor FcγR IIb was negatively correlated withALT、AST. FcγRs expression levels maybe a marker to distinguish HBVimmune tolerant and clearance phase.