Soluble adhesion molecules and interleukin-2 receptor concentrations in patients with autoimmune chronic hepatitis.
OBJECTIVE
To test the hypothesis that elevated serum levels of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), (s)E-selectin, (s)P-selectin and soluble interleukin-2 receptor (sIL-2R) occur in patients with biochemically inactive autoimmune hepatitis (AICH) compared with controls. Such a finding would suggest continued immune activation, which in the long-term would contribute to the development of cirrhosis in such patients.


METHODS
sICAM-1, sVCAM-1, sE-selectin, sP-selectin and sIL-2R were measured in serum from 50 patients with AICH, divided into two groups according to whether their serum alanine aminotransferase (ALT) levels were normal (below 40 IU/l) or increased (above 40 IU/l). Fourteen healthy subjects served as controls. Eight patients were followed after the induction of remission with increased immunosuppressive therapy.


RESULTS
Elevated levels of sICAM-1, sVCAM-1 and sE-selectin were found in patients with AICH compared with controls, independent of their ALT concentration. Only sICAM-1 was significantly elevated in the patients with active disease compared with patients with inactive disease. sIL-2R concentrations were significantly higher in patients with active disease (ALT above 40 IU/l) compared with controls. sP-selectin concentrations were similar in controls and patients with AICH. In patients with clinical and biochemical relapse, increased steroid therapy was followed by a significant reduction in sICAM-1, sVCAM-1 and sIL-2R. The response of sE-selectin was more variable. sICAM-1 remained elevated in five of the eight patients treated with increased steroid therapy despite normalization of their transaminase levels, sIL-2R, sE-selectin and sVCAM-1 levels. In 52% of patients with biochemically inactive AICH (ALT below 40 IU/l), sICAM-1 was above the control range.


CONCLUSIONS
These data suggest that patients with AICH have ongoing immune activation despite biochemically inactive disease. This may result in low grade hepatic inflammation and may explain the progression to cirrhosis in patients with AICH despite immunosuppressive therapy.
Simpson
K J
KJ
Department of Medicine, University of Edinburgh, Royal Infirmary, UK.
Jones
A L
AL
Forbes Howie
A
A
Hayes
P C
PC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D015703:Antigens, CD / Q000097:blood*; D001327:Autoimmune Diseases / Q000097:blood* / Q000188:drug therapy; D001379:Azathioprine / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000097:blood*; D002908:Chronic Disease; D019040:E-Selectin; D005260:Female; D005916:Globulins / Q000032:analysis; D006505:Hepatitis / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008103:Liver Cirrhosis / Q000097:blood / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000097:blood*; D011239:Prednisolone / Q000627:therapeutic use; D011971:Receptors, Immunologic / Q000032:analysis*; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D012074:Remission Induction; D012709:Serum Albumin / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D005916:Globulins; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D012709:Serum Albumin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D011239:Prednisolone; D000410:Alanine Transaminase; D001379:Azathioprine