title: GAD-alum treatment in patients with type 1 diabetes and the subsequent effect on GADA IgG subclass distribution, GAD65 enzyme activity and humoral response.
abstract: We have previously shown that two injections of 20 μg GAD-alum to recent onset type 1 diabetic children induced GADA levels in parallel to preservation of insulin secretion. Here we investigated if boosted GADA induced changes in IgG1, 2, 3 and 4 subclass distributions or affected GAD(65) enzyme activity. We further studied the specific effect of GAD-alum through analyses of IA-2A, tetanus toxoid and total IgE antibodies. Serum from children receiving GAD-alum or placebo was collected pre-treatment and after 3, 9, 15 and 21 months. At 3 months a reduced percentage of IgG1 and increased IgG3/IgG4 were detected in GAD-alum treated. Further, IA-2A, IgE and tetanus toxoid antibodies, as well as GAD(65) enzyme activity, were unaffected confirming the specific effect of treatment. In the GAD-alum group, higher pre-treatment GADA were associated to more pronounced C-peptide preservation. The induced IgG3/IgG4 and reduced IgG1 suggest a Th2 deviation of the immune response.
authors.affiliation: Division of Paediatrics and Diabetes Research Centre, Department of Clinical and Experimental Medicine, Linköping University, Sweden. mikael.cheramy@liu.se
authors.forename: Mikael
authors.initials: M
authors.lastname: Chéramy
authors.forename: Camilla
authors.initials: C
authors.lastname: Skoglund
authors.forename: Ingela
authors.initials: I
authors.lastname: Johansson
authors.forename: Johnny
authors.initials: J
authors.lastname: Ludvigsson
authors.forename: Christiane S
authors.initials: CS
authors.lastname: Hampe
authors.forename: Rosaura
authors.initials: R
authors.lastname: Casas
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000293:Adolescent; D000534:Alum Compounds / Q000627:therapeutic use*; D000906:Antibodies / Q000097:blood / Q000276:immunology; D019540:Area Under Curve; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D055162:Biocatalysis / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000276:immunology* / Q000628:therapy*; D004311:Double-Blind Method; D005968:Glutamate Decarboxylase / Q000276:immunology / Q000378:metabolism* / Q000627:therapeutic use*; D006801:Humans; D007106:Immune Sera / Q000276:immunology / Q000494:pharmacology; D056724:Immunity, Humoral / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D016233:Immunotherapy, Active / Q000379:methods*; D013745:Tetanus Toxoid / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000906:Antibodies; D001323:Autoantibodies; D002096:C-Peptide; C096322:ICA512 autoantibody; D007106:Immune Sera; D007074:Immunoglobulin G; D013745:Tetanus Toxoid; C041524:aluminum sulfate; D007073:Immunoglobulin E; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2