PD-1 Regulated Immune Tolerance On AIH-Cirrhosis Patients Post-Splenectomy

Background: Autoimmune hepatitis(Autoimmune hepatitis,AIH)is an immune disorder related to liver injury with raising prevalence in recent years.Some patients could have fulminant hepatitis and even advance into cirrhosis.Steroid and immune suppression drugs could have effect on the disease;however,there are contraindications of the drug use in cirrhosis patients.Splenectomy is a traditional method for treating complication of cirrhosis patients,changing the hypersplenism status.In our recent study,it showed that splenectomy could not only have supported effect for the patients,but also change the immune status of the patients due to that spleen is one of the major site for immune regulation and tolerance.In this study,we will analysis of the patients' immune function and further construct animal models,to further clarify the immune check point pathway alteration post-surgery as an induction of immune tolerance scenario.Patients and Methods: We enrolled patients diagnosed as chronic hepatitis(HBV)with cirrhosis,chronic hepatitis with cirrhosis(HBV)and post-splenectomy,AIH with cirrhosis,AIH with cirrhosis and post-splenectomy in our medical center from Department of Gastroenterology and Hepatology,and Department of Surgery.We collected the basic clinic information,lab tests results,liver pathology and peripheral blood cells to study immune cells subtypes.We further constructed animal models using Con A injection described as before.We generally study the T cell exhaustion status using FACS and try to explore the internal signal protein interaction using EMSA methods to illustrate the NF-?B regulation mechanism.Results: Splenectomy could enhance the white blood cells and platelets count significantly.AIH patients could have lower cytokines and chemokines expression after surgery,also had T cell repression effects.Post-splenectomy patients had elevated M2 c type macrophage,which showed immune suppression phenotype.Although AIH patients have more CD8+T cell infiltration in the liver tissue,after splenectomy,they have more exhaustion type of CD8+T cells in the blood.These cells also had regulated other immune check point markers such as CD160,4-1BB expression,which suggested that enhancement of CD8+T cells could not all belongedto self-damaged,their phenotype and function could be altered when immune intervention method,such as splenectomy was performed.Furthermore,immune regulation markers and steroid-responsive signal GITR(glucocorticoid—induced tumor necrosis factor receptor)were also up-regulated with more p50 interaction of NF-?B transcription factor,thus considering enhancement of immune suppression function.Conclusion: Splenectomy could ameliorate the immune disturbance in AIH cirrhosis patients,providing chance for further immune suppression drug therapy.However,splenectomy itself could promote immune tolerance function per inducing immune suppression subtype of macrophage and CD8+T cell exhaustion.More homogenous p50 interaction of key transcription factor NF-?B could contribute to the differentiation of immune cell phenotypes in above scenario.