Clinical characteristics of patients with IgG4-associated type I autoimmune hepatitis

Abstract

Objective To investigate the expression of IgG4 in liver tissues of patients with type Ⅰ autoimmune hepatitis (AIH) and to analyze the clinical manifestation,biochemical indexes,immunological genetic features,pathological characteristics and the effects of immunosuppressive therapy.Methods From March 2012 to July 2013,45 patients diagnosed as type Ⅰ AIH were enrolled.Immunostaining of CD38,IgG and IgG4 in liver tissue slices was performed,inflammation grade G and fibrosis stage S were determined.At the same time,serological indexes (alanine aminotransferase (ALT),aspartate transaminase (AST),alkaline phosphatase (ALP),IgG,antinuclear antibody (ANA) titer,antibodies to asialoglycoprotein receptor (ASGPRAb)) of the patients were collected,serum IgG4 was tested and the response to immunosuppressive therapy was observed.Wilcoxon rank sum test and t test were performed for quantitative data comparison.Spearman correlation coefficient was used for correlation analysis.Results Among 45 patients with type Ⅰ AIH,five patients (11.1％) were IgG4 associated AIH (IgG4-AIH group).There were no significant differences in age,gender,biochemical indexes (serum levels of ALT,AST,ALP),immunity indexes (serum levels of IgG,ANA titer,ASGPRAb) and degree of liver fibrosis between patients with IgG4-associated AIH and classical AIH (40 cases) (all P＞ 0.05).Compared with classical AIH group (18.3(6.7) mg/L).The serum level of IgG4 of IgG4 AIH group was 25.8(9.2) mg/L,which significantly increased (Z=-2.041,P＜0.05).However,there was no significant difference in serum level of IgG4 between the two groups (P＞0.05).There was no correlation between the number of infiltrated IgG4 positive plasma cells and the serum level of IgG4 (r=0.311,P=0.279).The inflammation in the liver tissues of IgG4-AIH group was more significant compared with that of classic AIH group (H=4.120,P＜0.05).The number of CD38' or IgG+ plasma cells was larger compared with that of classical AIH (CD38(39.3(13.5)/high power field (HPF) vs (21.3(8.8))/HPF,IgG(39.3 (14.0))/HPFvs (18.5(8.9))/HPF;Z ＝-3.561 and-3.584,both P＜0.01).The number of IgG4+ plasma cells in liver tissues was positively correlated with the number of CD38+ or IgG+ plasma cells (r=0.884 and 0.791,both P＜0.01).Conclusions Among patients with type Ⅰ AIH,the incidence of IgG4-associated AIH was not high.The serum level of IgG4 did not significantly increase in these patients.However,the histological inflammation activity was significant along with many CD38+ or IgG+ plasma cells infiltration. Key words: Hepatitis, autoimmune; IgG4; IgG4-related disease; Pathology, clinical