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Changes in GAD65Ab-Specific Antiidiotypic Antibody Levels Correlate with Changes in C-Peptide Levels and Progression to Islet Cell Autoimmunity.

Author:
  • E Ortqvist
  • B Brooks-Worrell
  • Kristian Lynch
  • J Radtke
  • L M Bekris
  • I Kockum
  • Carl-David Agardh
  • Corrado Cilio
  • ÅsaLinda Lethagen
  • B Persson
  • Åke Lernmark
  • J Reichow
  • S Oak
  • J P Palmer
  • C S Hampe
Publishing year: 2010
Language: English
Pages: 310-318
Publication/Series: The Journal of clinical endocrinology and metabolism
Volume: 95
Document type: Journal article
Publisher: The Endocrine Society

Abstract english

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 mug 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 beta-cell function may provide a novel marker for the progression of autoimmune diabetes.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Diabetes and Celiac Unit
  • Diabetes - Cellular Autoimmunity
  • ISSN: 1945-7197
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79

60:11:015

Jan Waldenströms gata 35, Malmö

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00