Changes in GAD65Ab-specific antiidiotypic antibody levels correlate with changes in C-peptide levels and progression to islet cell autoimmunity

J Clin Endocrinol Metab. 2010 Nov;95(11):E310-8. doi: 10.1210/jc.2010-0785. Epub 2010 Aug 4.


Context: The previously reported absence of 65-kDa glutamate decarboxylase antibody (GAD65Ab)-specific antiidiotypic antibodies (anti-Id) in type 1 diabetes (T1D) patients at clinical onset could be due to an inability to mount an antibody response to GAD65Ab or a longitudinal decline in anti-Id levels.

Objective and design: We investigated anti-Id levels in longitudinal samples obtained from T1D patients (n = 41) (clinical diagnosis - 12 months), and latent autoimmune diabetes in adults (LADA) patients (n = 32) who received alum-formulated human recombinant GAD65 (baseline - 12 months). We also determined anti-Id levels in a small cohort of Type 2 diabetes patients during their development of autoimmune T cell responses.

Results: At clinical onset T1D patients presented no or low anti-Id levels. However, 22/41 T1D patients showed ≥50% increase in GAD65Ab-specific anti-Id levels during follow-up; peaking at 3 (n = 1), 6 (n = 10), 9 (n = 10), or 12 (n = 1) months. Increasing anti-Id levels marked patients who experienced a temporary increase in C-peptide levels. Anti-Id levels correlated significantly with glycated hemoglobin and C-peptide levels at 6 and 9 months (P values ranged from <0.001 to <0.05). In LADA patients receiving placebo, anti-Id levels declined in seven of nine patients, whereas four of five patients receiving 20 μg alum-formulated human recombinant GAD65 showed increasing anti-Id levels. Changes in anti-Id and C-peptide levels closely correlated (P < 0.0001). The significant decline in anti-Id levels (P = 0.03) in T2D patients developing T cell autoimmune responses supports our hypothesis that declining anti-Id levels are associated with developing islet autoimmunity.

Conclusions: The close association between GAD65Ab-specific anti-Id levels and β-cell function may provide a novel marker for the progression of autoimmune diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Analysis of Variance
  • Antibodies, Anti-Idiotypic / blood*
  • Antibodies, Anti-Idiotypic / immunology
  • Autoimmunity / immunology*
  • C-Peptide / blood*
  • C-Peptide / immunology
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / immunology
  • Disease Progression*
  • Female
  • Glutamate Decarboxylase / blood*
  • Glutamate Decarboxylase / immunology
  • Humans
  • Infant
  • Islets of Langerhans / immunology*
  • Male
  • Prospective Studies


  • Antibodies, Anti-Idiotypic
  • C-Peptide
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2