Intrahepatic IgG/IgM plasma cells ratio helps in classifying autoimmune liver diseases

Abstract 

Background/Aim

Plasma cells infiltrate in the liver is a prototype lesion of autoimmune liver diseases. The possible role of plasma cells isotyping (IgM and IgG) in the liver in the diagnostic definition of autoimmune liver disease, and particularly in variant syndromes such as autoimmune cholangitis and the primary biliary cirrhosis/autoimmune hepatitis overlap syndrome, is less defined.

Methods

We analysed the clinical, serological and histological features of 83 patients with autoimmune liver disease (40 primary biliary cirrhosis, 20 autoimmune hepatitis, 13 primary sclerosing cholangitis, 4 autoimmune cholangitis and 6 overlap syndrome) compared to 34 patients with chronic hepatitis C and evaluated the expression of IgM and IgG plasma cells in their liver by immunostaining.

Results

By Spearman's correlation, the mean-counts of IgM plasma cells in portal tracts were significantly correlated with female gender, serum alkaline phosphatase, gamma-glutamyl transferase and IgM values, positivity for anti-mitochondrial antibody-M2 and, on liver biopsy, with bile duct changes, orcein-positive granules and granulomas. Whereas IgG plasma cells resulted more correlated with alanine aminotransferase levels. IgG/IgM ratio lower than 1 was found no only in primary biliary cirrhosis but also in all patients with autoimmune cholangitis. Conversely, all patients with overlap syndrome showed IgG/IgM ratio higher than 1.

Conclusion

Immunostaining for IgM and IgG plasma cells on liver tissue can be a valuable parameter for better diagnosis of autoimmune liver disease and also for variant or mixed syndromes.

Abbreviations: AIC, autoimmune cholangitis, AIH, autoimmune hepatitis, AILD, autoimmune liver disease, AMA, anti-mitochondrial antibody, ANA, antinuclear antibody, AP, alkaline phosphatase, GGT, gamma-glutamyl transferase, LKM, liver kidney microsomal type 1 antibody, M2, E2 subunit of pyruvate dehydrogenase mitochondrial auto-antigen, OS, overlap syndrome, PBC, primary biliary cirrhosis, PSC, primary sclerosing cholangitis, SMA, smooth muscle antibody, VS, variant syndrome

Keywords: Autoimmune cholangitis, Autoimmune hepatitis, IgG plasma cells, IgM plasma cells, Immunostaining, Liver biopsy, Overlap syndromes, Portal infiltrate, Primary biliary cirrhosis