title: Cellular and humoral immune responses in type 1 diabetic patients participating in a phase III GAD-alum intervention trial.
abstract: OBJECTIVE
  GAD formulated in aluminum hydroxide (GAD-alum) has previously been shown to induce preservation of residual insulin secretion in recent-onset type 1 diabetes, but recent phase II and III GAD-alum trials failed to reach primary outcomes. The European phase III study was therefore closed after 15 months, and only a minority of patients completed the 30 months of follow-up.
  
  
  METHODS
  This study aimed to characterize cellular and humoral responses in the Swedish patients (n = 148) participating in the phase III trial, receiving four (4D) or two (2D) GAD-alum doses or placebo. Serum GAD65 antibody (GADA) levels, GADA IgG1-4 subclass distribution, cytokine secretion, and proliferative responses in peripheral blood mononuclear cells (PBMCs) were analyzed.
  
  
  RESULTS
  The GAD65-induced cytokine profile tended to switch toward a predominant Th2-associated profile over time both in the 2D and 4D group. The groups also displayed increased GADA levels and PBMC proliferation compared with placebo, whereas GADA IgG subclass distribution changed in 4D patients.
  
  
  CONCLUSIONS
  Both 2D and 4D patients displayed GAD65-specifc cellular and humoral effects after GAD-alum treatment, but at different time points and magnitudes. No specific immune markers could be associated with treatment efficacy.
authors.affiliation: Corresponding author: Mikael Chéramy, mikael.cheramy@liu.se.
authors.forename: Stina
authors.initials: S
authors.lastname: Axelsson
authors.forename: Mikael
authors.initials: M
authors.lastname: Chéramy
authors.forename: Linda
authors.initials: L
authors.lastname: Akerman
authors.forename: Mikael
authors.initials: M
authors.lastname: Pihl
authors.forename: Johnny
authors.initials: J
authors.lastname: Ludvigsson
authors.forename: Rosaura
authors.initials: R
authors.lastname: Casas
mesh_terms: D000328:Adult; D000534:Alum Compounds / Q000008:administration & dosage*; D001323:Autoantibodies / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D007328:Insulin / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D000534:Alum Compounds; D001323:Autoantibodies; D007074:Immunoglobulin G; D007328:Insulin; C041524:aluminum sulfate; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2