The significance of stimulation in the leucocyte migration test as an indicator of cellular hypersensitivity--studies using Tamm-Horsfall glycoprotein as antigen.

To determine whether stimulation of leucocyte migration in the presence of an antigen is a reliable indicator of sensitization, the results of leucocyte migration using a kidney antigen (Tamm-Horsfall glycoprotein) were compared with those of lymphocyte transformation using the same antigen and with the lymphocyte cytotoxicity for cells known to synthesize this antigen. There was a close correlation between the results of all three tests and these findings strongly suggest that the stimulation of leucocyte migration as an immunological phenomenon was as valid as inhibition in demonstrating sensitization.

Cell-mediated immunity to human Tamm-Horsfall glycoprotein in autoimmune liver disease with renal tubular acidosis.

Cell-mediated immune responses to Tamm-Horsfall glycoprotein isolated from human urine were investigated using the leucocyte migration test. Abnormal responses were found in 91% of patients with active chronic hepatitis or primary biliary cirrhosis with an associated renal tubular acidosis (R.T.A.) but in only 19% of those without R.T.A. In nearly all of a group of patients without autoimmune liver disease and in a control group of normal subjects results were within normal limits. In addition, using an immunofluorescent technique with rabbit antibody to human Tamm-Horsfall glycoprotein, it was possible to show the presence in human liver cell membrane of material reacting immunologically as Tamm-Horsfall. These findings suggest that the development of an immune response to this glycoprotein, initiated by release of cross-reacting antigens from damaged hepatocytes, could be the mechanism underlying the occurrence of R.T.A. in some patients with autoimmune liver disease.

Cellular immune responses to salivary antigens in autoimmune liver disease with sicca syndrome.

Twenty-six patients with primary biliary cirrhosis (PBC) and twenty-two with active chronic hepatitis (ACH) were examined for evidence of the sicca syndrome (keratoconjunctivitis sicca, xerostomia). Measurements of tear flow and total saliva flow showed that at least one sicca feature was present in twenty (77%) of the patients with PBC and ten (45%) of those with ACH. Examination of cellular immune responses to a protein fraction of normal human saliva using the leucocyte migration test showed sensitization to the saliva protein in twenty-three of the thirty cases with sicca syndrome but in only two of the eighteen in whom sicca features were not detected. Antisera raised in guinea-pigs against the saliva protein gave specific immunofluorescent staining of bile duct epithelial cells in sections of normal human liver. These findings suggest that damage to structures in the liver may lead to sensitization to various self-antigens which cross-react with other tissues in which a similar disease process may be consequently be initiated.

Leukocyte migration inhibition in response to biliary antigens in primary biliary cirrhosis, sclerosing cholangitis, and other chronic liver diseases.

The leukocyte migration inhibition test has been used to investigate cellular immune responses to antigens in a protein fraction (BPF) of normal human gallbladder bile in patients with a variety of intra- and extrahepatic diseases. Inhibition of leukocyte migration in the presence of BPF was observed in 30 (81%) of 37 patients with PBC, in 8 (80%) of 10 patients with sclerosing cholangitis, and in 7 (26%) of 27 patients with chronic active hepatitis. Only 1 of 31 patients with other liver diseases or with uncomplicated ulcerative colitis showed a similar response to BPF. The BPF was found to contain three antigens which were distinct from plasma proteins. Immunofluorescence studies revealed that one of these antigens appears to be derived from that part of the hepatocellular membrane which forms the bile canaliculus and that a second appears to be associated with the epithelial cell membranes of interlobular and septal bile ducts. The site of origin of the third antigen could not be established. It is suggested that cellular immune responses to biliary antigens could be involved in the progressive bile duct destruction of chronic biliary disease.