ABSTRACT
Autoimmune mechanisms are postulated to play a role in the development and progression of dysimmune neuropathies (DN). We investigated the relation between lymphocyte number and marker expression, and disease activity in 20 patients with DN under intravenous immunoglobulins (IVIg) treatment. B- and T-lymphocyte markers were studied by flow cytometry of the expression of CD5, CD25, CD23 and CD38 markers on B cells and of CD3, CD4 and CD8 markers, respectively. These parameters were compared with those obtained from matched healthy volunteers. The proportions of CD38+ B cells were higher in patients compared with those of controls. Proportions of activated CD4+ and CD8+ T cells were comparable in peripheral blood mononuclear cells of patients and controls, but a significant reduction of the absolute numbers of CD3+, CD4+ and CD8+ cells were observed in DN patients. The percentages of CD25+ memory T cells were instead significantly increased in DN patients. Lastly, T-cell reduction and the CD19/CD38 ratio over total B (CD19+) cells directly correlated with a poor response to IVIg therapy. In DN, whereas T-cell number is reduced, activated T and B cells are increased, thus suggesting an intrinsic defect of the immune response.
Subject(s)
B-Lymphocyte Subsets/pathology , Immunoglobulins, Intravenous/therapeutic use , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/immunology , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/therapy , Polyradiculoneuropathy/immunology , Polyradiculoneuropathy/therapy , T-Lymphocyte Subsets/pathology , Adult , Aged , B-Lymphocyte Subsets/metabolism , Biomarkers/blood , Female , Humans , Lymphocyte Activation , Lymphocyte Count , Male , Middle Aged , Polyradiculoneuropathy/pathology , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/pathology , T-Lymphocyte Subsets/metabolismABSTRACT
A conjugate of adenine arabinoside monophosphate with lactosaminated albumin produced vacuoles in hepatic cells of rats and mice when given at doses 5-10 times higher than that (35 mg/kg) capable of inhibiting hepatitis B virus replication in patients with chronic hepatitis B. The vacuoles were due to the swelling of secondary lysosomes probably caused by incapacity of the lysosomal enzymes to rapidly digest large amounts of conjugate into products able to cross the lysosomal membrane. Although vacuoles progressively disappeared when conjugate administration was discontinued, the present observation suggests caution in giving the conjugate to man at daily doses higher than 35 mg/kg.
Subject(s)
Liver/cytology , Serum Albumin/pharmacology , Vacuoles/ultrastructure , Vidarabine/pharmacology , Animals , Dose-Response Relationship, Drug , Female , Liver/drug effects , Liver/ultrastructure , Lysosomes/ultrastructure , Male , Mice , Microscopy, Electron , Rats , Rats, Wistar , Serum Albumin/metabolism , Tritium , Vidarabine/metabolismABSTRACT
A simple and sensitive method for determining concentrations, in plasma, of adenine arabinoside monophosphate conjugated with lactosaminated albumin is described. It permits the measurement of as little as 0.02 micrograms coupled drug/ml and has considerable advantages over the radioimmunoassay previously used for the same purpose.
