Immunohistochemical analysis of inflammation in primary sclerosing cholangitis.
OBJECTIVE
There are only limited data about the nature of the mononuclear infiltrate surrounding the affected biliary canaliculi in primary sclerosing cholangitis (PSC). The aim of this study was to characterize the composition of the mononuclear infiltrate and to detect signs of activation/ proliferation among the various subpopulations involved. Furthermore the putative role of the biliary epithelium as antigen presenting cells (APC) was assessed.


METHODS
Liver biopsies of 14 PSC patients were analysed. Seven liver specimens of non-inflammatory liver disease (NIL) patients with hepatocellular carcinoma or metastasis from colorectal carcinoma, as well as eight liver biopsies of primary biliary cirrhosis (PBC) patients, served as controls. Paraffin embedded material was stained with GB7, anti-CD3, anti-CD20, anti-CD45RO. Deep frozen sections were stained with anti-CD4, anti-CD8, anti-CD25, anti-CD86, anti-HLA-DR, anti-IFNgamma, anti-IL4, anti-ICAM1 and anti-alpha4beta7. Stainings were scored by two pathologists using a semiquantitative scale.


RESULTS
The portal infiltrate was found to consist mainly of CD3+CD45RO+ cells. Few cells expressed activation or proliferation markers in any of the liver specimens. In the PSC-material, significantly more of the infiltrative lymphocytes were positive for the integrin alpha4beta7, as compared to hardly any positive cells in the NIL-group (P < 0.001) and < 10% in the PBC-specimens (P < 0.01). Variable HLA-DR expression of the biliary epithelium was observed in all groups, however, without co-expression of ICAM1 or B7.2.


CONCLUSIONS
The portal infiltrate in PSC liver histology specimens appears to consist mainly of non-activated memory T-lymphocytes, a substantial proportion of which expresses the gut-homing integrin alpha4beta7. An antigen-presenting role for the biliary epithelium could not be demonstrated.
Ponsioen
C Y
CY
Department of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
Kuiper
H
H
Ten Kate
F J
FJ
van Milligen de Wit
M
M
van Deventer
S J
SJ
Tytgat
G N
GN
D000328:Adult; D015703:Antigens, CD; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002455:Cell Division; D015209:Cholangitis, Sclerosing / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008113:Liver Neoplasms / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000473:pathology
D015703:Antigens, CD