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Anti-lymphocytic antibodies (ALA) have been described in a variety of autoimmune disorders. We have investigated the presence of ALA in autoimmune chronic active hepatitis (aCAH) starting in childhood. Using a modified Terasaki technique ALA were found in 17 of 18 patients with aCAH but in only one of 15 patients with alpha-1-anti-trypsin deficiency or Wilson's disease and three of 27 aged-matched healthy controls (P < 0.0005 for both). Sera from 12 patients with uncontrolled aCAH had significantly higher cytotoxicity values than sera from six children with inactive disease (P < 0.01). ALA were directed to T but not B lymphocytes and were not reactive with specific HLA antigens. No preferential killing was observed against CD4 or CD8 positive T lymphocytes. Characterization of ALA revealed them to be cold-reactive IgM. The possible role of ALA in aCAH is discussed. [ABSTRACT FROM AUTHOR]

An indirect immunofluorescence technique was used to investigate the immunoglobulin class, IgG subclass, light chain type and complement fixing ability of anti-liver kidney microsomal antibody (anti-LKM) in the sera of six children and five adults with autoimmune chronic active hepatitis (aCAH), Anti-LKM titres ranged from 1/80 to 20,480. In the children, the antibody belonged to the IgG1 subclass alone (titre l/80-1/20,480) and was able to fix complement (titre 1/40 -1/5120). In the adult group, antibody belonged to the IgG1 subclass in three cases (titre 1 40-1 640 whilst two belonged to both IgG1 (titre 1/640) and lgG4 (titre 1/40, 1/640). Such subclass restriction is similar to that found in other autoimmune disorders and may be genetically determined. Investigation of' the light chain constituent of anti-LKM revealed that the kappa to lambda ratio was consistent with a polyclonal antibody response. To investigate the nature of the antigen to which anti-LKM is directed, the ability of these sera to bind to the surface membrane of isolated human hepatoma cells (Alexander cells) was investigated. Four of the eleven sera showed significant binding activity. Prior incubation of these four sera with Alexander cells abolished their membrane binding activity, but did not alter the anti-LKM titre. These results suggest that anti-LKM binds to cytoplasmic constituents alone and does not cross-react with surface antigens. [ABSTRACT FROM AUTHOR]

Con A stimulated suppressor cell function and the proportion of suppressor T cells were reduced in children with untreated chronic active hepatitis (CAH) but were normal in corticosteroid treated CAH patients, patients with severe acute hepatitis and inactive chronic liver disease. Adults with CAH also have defective suppressor function hut a normal proportion of T suppressor cells. This difference may account for the observation that relapse after treatment withdrawal is less frequent in children than in adults. [ABSTRACT FROM AUTHOR]

Proportion of T cell subsets, spontaneous and PWM stimulated immunoglobulin production by peripheral blood lymphocytes and concanavalin A- (Con A) stimulated suppressor cell activity on immunoglobulin production by B cells was studied in 37 infants and children, to investigate changes of these parameters with age. Proportion of suppressor/cytotoxic (T8+) T lymphocytes was significantly lower in children below the age of 5 years, while there was no difference in proportion of total T lymphocytes (T3+) and helper/inducer (T4+) T cells. Spontaneous production and secretion of IgG and IgM by lymphocytes from children of all age groups was similar to that found in adults, but lymphocytes of children below the age of 10 years showed a low response to PWM stimulation. The activity of Con A-induced suppressor cells in inhibiting B cells producing immunoglobulins was almost absent in infancy, gradually increased during childhood and reached adult levels in teenagers. A significant association between the proportion of T8+ cells and Con A-induced suppression of B cell proliferation and a relationship between T4+ cells and spontaneous Ig production indicated the increasing maturity with respect to both number and function of peripheral blood lymphocyte subsets with advancing age. [ABSTRACT FROM AUTHOR]

Defective opsonization of heat-killed baker's yeast was found in all 14 children with fulminant hepatic failure (FHF) but returned to normal in two who recovered and was normal in six mothers of patients. Yeast opsonization was significantly correlated with factor B activity of FHF serum but not with other components of classical or alternative pathways of complement. Reconstitution and family studies suggested that defective yeast opsonization in FHF is secondary and, although dependent on factor B activity, is qualitatively and quantitatively similar to that of primary yeast opsonization deficiency. These findings suggest that the factors responsible for opsonization of yeasts, or their regulation, are synthesized or controlled by the liver. [ABSTRACT FROM AUTHOR]

In a micrototoxicity assay, lymphocytes from ten out of sixteen patients with HBsAg-negative chronic active hepatitis have been shown to be cytotoxic to autologous hepatocytes isolated from percutaneous liver biopsies. This cytotoxicity was demonstrable in all six untreated patients but in only four out of ten receiving immunosuppressive treatment, the presence of cytotoxicity showing a significant association with the activity of the disease assessed histologically. The addition of excess purified lipoprotein (LSP), derived from the hepatocyte plasma membrane, blocked the reaction in all cytotoxic cases, indicating that LSP was the major target antigen. Enriched fractions of T cells were cytotoxic in only one case, whereas non-T cell fractions were cytotoxic in the other ten cases investigated in this way. For optimum T cell cytotoxicity, effector and target cells must share histocompatibility determinants and the results of this study using an autologous system show conclusively that the lymphocyte cytotoxicity found in HBsAg-negative chronic active hepatitis is mediated by a non-T cell population. [ABSTRACT FROM AUTHOR]