Value Of Immunoglobulin Levels In Serum And Liver Tissue In Identification And Curative Effect Evaluation Of Autoimmune Liver Disease

Background and objective:Autoimmune liver disease(AILD) is a group of hepatobiliary diseases associated with autoimmune disorders,including autoimmune hepatitis(AIH),primary biliary cholangitis(PBC) represented by bile duct damage and cholestasis,primary sclerosing cholangitis(PSC) and overlap syndromes.This group of diseases has a higher incidence of AIH,PBC and AIH-PBC overlap syndrome,while PSC is rare.In clinical practice,the early manifestations are abnormal liver function indicators and no expression of specific autoantibodies when the clinical manifestations of diseases are not very typical or overlap,making the diagnosis and differential diagnosis more difficult,easily leading to missed diagnosis and even misdiagnosis,affecting the treatment.At present,the blood biochemical indicators,AILD-related antibody detection and liver tissue biopsy are used to diagnose and identify diseases,but the accuracy of the diagnosis is affected to some extent due to the lack of specific markers.To improve the accuracy of the identification and diagnosis of PBC,AIH and AIH-PBC overlap syndrome,the clinical manifestations,immunological features and pathological features of patients with AILD in three hospital in the last decade were retrospectively analyzed in this study to further deepen the understanding of the clinical manifestations and histological features of AILD.At the same time,the expression of IgM,IgG and IgG4 in serum and liver tissues of PBC patients,AIH and AIH-PBC overlap syndrome were detected by enzyme-linked immunosorbent assay(ELISA) and immunohistochemistry,the differences in the expression of immunoglobulin in the serum before and after treatment were compared,and the clinical value of this indicator in AILD diagnosis,differential diagnosis and monitoring was further explored.Methods:1.Analysis of clinical and pathological features of patients with AILDThe age composition,sex ratio,clinical symptoms,signs,biochemical indica-tors,autoantibody expression,immunoglobulin expression levels,histopathological features and stage were reviewed among various diseases of AILD(AIH,PBC,PSC,AIH-PBC overlap syndrome) in the past decade.2.Value of immunoglobulin levels in identification and curative effect Evaluation of AILDThe patients with AILD were divided into AIH group,PBC group and AIH-PBC overlap group.Serum IgG,IgM and IgG4 levels were measured before and after treatment via ELISA.The expression levels of IgG,IgM and IgG4 in the liver tissue before treatment were examined,the differences in IgG,IgM and IgG4 serum and liver tissue levels were compared in patients with AILD,and the differences in IgG,IgM and IgG4 serum levels before and after treatment were observed.3.Clinical and pathological features of IgG4-related AIHAIH was divided into the classical AIH group and the IgG4-related AIH group.The clinical manifestations,biochemical parameters and histological differences were compared between the two groups of AIH patients,and the value of IgG4 in AIH diagnosis,differential diagnosis and evaluation was analyzed.Results:1.Analysis of clinical and pathological features of patients with AILD(1)A total of 320 patients with AILD were collected,with the male-female ratio of about 1:6,including 80 cases in the AIH group,204 cases in the PBC group,6 cases in the PSC group,and 30 cases in the AIH-PBC overlap group.(2)The clinical manifestations of AILD patients included the fatigue,anorexia,jaundice,abdominal distension,itching,nausea and hepatomegaly;in terms of the serum biochemical indexes,AIH group had elevated ALT,AST and serum IgG,elevated ALP,GGT and IgM in PBC group,and elevation of the above indexes in AIH-PBC overlap group;AIH patients were characterized by positive expression of ANA and SMA,PBC patients were characterized by positive expression of AMA and AMA-M2,while AIH-PBC overlap syndrome patients were characterized by positive expression of ANA and AMA-M2.(3)The main pathological features of the AIH group were interfacial inflammation,lymphatic infiltration in the portal vein,and bridging necrosis in some patients.The main pathological features of the PBC group were granuloma formation and small bile duct loss,while the AIH-PBC overlap group had such pathological manifestations as hepatocyte injury and bile duct injury.2.Value of immunoglobulin levels in identification and curative effect evaluation of AILD(1)A total of 102 AILD patients were enrolled,including 38 cases in the AIH group,52 cases in the PBC group,and 12 cases in the AIH-PBC overlap group.The women accounted for 84.2%,86.5% and 83.3%,respectively.(2)The serum IgG4 level in AIH group was significantly higher than that in PBC group and AIH-PBC group.The IgG level was slightly higher than that in AIH-PBC group,while the serum IgM level in PBC group was significantly higher than that in AIH group and AIH-PBC group.(3)Immunohistochemistry revealed that positive signals of IgG4,IgG and IgM were expressed in the cytoplasm of hepatic plasma cells,showing brownish yellow;AIH group had more IgG positive cells(32/38,84.2%),and some AIH cases had more IgG4 positive cells(7/38,18.4%).in the PBC group,The number of IgM positive cells was larger(45/52,86.5%),and the AIH-PBC overlap group had more positive expression of IgG(9/12,75%) and IgM(7/12,58.3%).There were significant differences in IgG and IgM positive cell count among the three groups(P<0.05).(4)All patients received treatment.Serum biochemical parameters were assessed at 12 and 24 weeks after follow-up.Serum ALT,AST,ALP and GGT levels were statistically significant(P<0.05).The levels of IgG and IgG4 were significantly lower in AIH patients after treatment than those before treatment.The levels of IgM and TBIL in PBC patients were lower than those before treatment,and the differences were statistically significant(P<0.05).The IgG and IgM levels were reduced in patients with AIH-PBC overlap syndrome compared with those before treatment,and the differences were statistically significant(P<0.05).The follow-up period lasted for 12 weeks and 24 weeks.With the treatment,serum immunoglobulins showed significant improvement compared with that before treatment.3.Clinical and pathological features of IgG4-related AIH(1)Among 38 patients with AIH,7 patients had elevated serum IgG4 level and IgG4 staining positive in liver tissue,which were classified into IgG4-AIH group,and the remaining 31 patients were classified into classical AIH group.There were no significant differences in the liver function index and ANA positive rate between the two groups,and the IgG level of serum in IgG AIH group was significantly increased.(2)Liver histological inflammation in the IgG4-AIH group was severer than that in the classical AIH group,and there was no significant difference in the fibrosis level between the two groups.Conclusion:1.The incidence of AILD in this study shows an increasing trend,mainly AIH,PBC and AIH-PBC overlap syndrome,but PSC is rare.It frequently occurs in middle-aged women aged above 40 years old.2.The serum IgG and IgG4 levels in patients with AIH are higher than those in patients with PBC and AIH-PBC overlap syndrome.PBC patients have a higher serum IgM level,and the decreased levels of IgG,IgG4 and IgM are associated with treatment response,so they can be used as indicators for differential diagnosis and prognosis in each group.3.IgG is mainly expressed in the plasmocytes in the portal area in AIH patients,IgM is mainly expressed in the plasmocytes in the portal area in PBC patients,and IgG and IgM are mainly expressed in the portal area in patients with AIH-PBC overlap syndrome.Detection of IgG and IgM in liver tissue is helpful for the diagnosis and identification of AILD.4.The level of IgG4 in serum and liver tissues of IgG4-AIH patients is significantly increased.The liver pathological examination showed the more obvious inflammatory activity,but the clinical manifestations and biochemical indexes had no significant differences between IgG4-AIH and classical AIH.