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GAD Autoantibody Affinity in Adult Patients With Latent Autoimmune Diabetes, the Study Participants of a GAD65 Vaccination Trial

Krause, Stephanie; Landherr, Ulrike; Agardh, Carl-David LU ; Hausmann, Simone; Link, Katarina LU ; Hansen, Jesse M.; Lynch, Kristian F.; Powell, Michael; Furmaniak, Jadwiga and Rees-Smith, Bernard, et al. (2014) In Diabetes Care 37(6). p.1675-1680
Abstract
OBJECTIVE Patients with latent autoimmune diabetes in adults (LADA) express autoantibodies against the 65-kDa isoform of GAD (GADA). Intervention with recombinant human GAD65 formulated with aluminium hydroxide (GAD-alum) given twice subcutaneously to LADA patients at intervals of 4 weeks was safe and did not compromise beta-cell function in a Phase II clinical trial. GADA affinity has been shown to predict progression to type 1 diabetes. Here, we asked whether GADA affinity was affected by the GAD65 antigen-specific vaccination and/or associated with beta-cell function in participants of this trial. RESEARCH DESIGN AND METHODS GADA affinity was measured in sera of 46 LADA patients obtained prior to the first week and 20 weeks after the... (More)
OBJECTIVE Patients with latent autoimmune diabetes in adults (LADA) express autoantibodies against the 65-kDa isoform of GAD (GADA). Intervention with recombinant human GAD65 formulated with aluminium hydroxide (GAD-alum) given twice subcutaneously to LADA patients at intervals of 4 weeks was safe and did not compromise beta-cell function in a Phase II clinical trial. GADA affinity has been shown to predict progression to type 1 diabetes. Here, we asked whether GADA affinity was affected by the GAD65 antigen-specific vaccination and/or associated with beta-cell function in participants of this trial. RESEARCH DESIGN AND METHODS GADA affinity was measured in sera of 46 LADA patients obtained prior to the first week and 20 weeks after the second injection with GAD-alum or placebo using competitive binding experiments with [I-125]-labeled and unlabeled human GAD65. RESULTS At baseline, GADA affinities ranged from 1.9 X 10(7) to 5.0 X 10(12) L/mol (median 2.8 X 10(19) L/mol) and were correlated with GADA titers (r = 0.47; P = 0.0009), fasting (r = 0.37; P = 0.01) and stimulated (r = -0.40; P = 0.006) C-peptide concentrations, and HbA(1c) (r = 0.39; P = 0.007). No significant changes in affinity were observed from baseline to week 24. Patients with GADA affinities in the lower first quartile (<4 X 10(9) L/mol) had better preserved fasting C-peptide concentrations at baseline than those with higher affinities (mean 1.02 vs. 0.66 nmol/L; P = 0.004) and retained higher concentrations over 30 months of follow-up (mean 1.26 vs. 0.62 nmol/L; P = 0.01). CONCLUSIONS Intervention with GAD-alum in LADA patients had no effect on GADA affinity. Our data suggest that patients with low GADA affinity have a prolonged preservation of residual beta-cell function. (Less)
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Contribution to journal
publication status
published
subject
in
Diabetes Care
volume
37
issue
6
pages
1675 - 1680
publisher
American Diabetes Association
external identifiers
  • wos:000337746100044
  • scopus:84901452215
ISSN
1935-5548
DOI
10.2337/dc13-1719
language
English
LU publication?
yes
id
074dcb0a-369b-4d21-b138-3551b1942faf (old id 4609636)
date added to LUP
2014-09-01 07:43:43
date last changed
2017-10-01 04:15:37
@article{074dcb0a-369b-4d21-b138-3551b1942faf,
  abstract     = {OBJECTIVE Patients with latent autoimmune diabetes in adults (LADA) express autoantibodies against the 65-kDa isoform of GAD (GADA). Intervention with recombinant human GAD65 formulated with aluminium hydroxide (GAD-alum) given twice subcutaneously to LADA patients at intervals of 4 weeks was safe and did not compromise beta-cell function in a Phase II clinical trial. GADA affinity has been shown to predict progression to type 1 diabetes. Here, we asked whether GADA affinity was affected by the GAD65 antigen-specific vaccination and/or associated with beta-cell function in participants of this trial. RESEARCH DESIGN AND METHODS GADA affinity was measured in sera of 46 LADA patients obtained prior to the first week and 20 weeks after the second injection with GAD-alum or placebo using competitive binding experiments with [I-125]-labeled and unlabeled human GAD65. RESULTS At baseline, GADA affinities ranged from 1.9 X 10(7) to 5.0 X 10(12) L/mol (median 2.8 X 10(19) L/mol) and were correlated with GADA titers (r = 0.47; P = 0.0009), fasting (r = 0.37; P = 0.01) and stimulated (r = -0.40; P = 0.006) C-peptide concentrations, and HbA(1c) (r = 0.39; P = 0.007). No significant changes in affinity were observed from baseline to week 24. Patients with GADA affinities in the lower first quartile (&lt;4 X 10(9) L/mol) had better preserved fasting C-peptide concentrations at baseline than those with higher affinities (mean 1.02 vs. 0.66 nmol/L; P = 0.004) and retained higher concentrations over 30 months of follow-up (mean 1.26 vs. 0.62 nmol/L; P = 0.01). CONCLUSIONS Intervention with GAD-alum in LADA patients had no effect on GADA affinity. Our data suggest that patients with low GADA affinity have a prolonged preservation of residual beta-cell function.},
  author       = {Krause, Stephanie and Landherr, Ulrike and Agardh, Carl-David and Hausmann, Simone and Link, Katarina and Hansen, Jesse M. and Lynch, Kristian F. and Powell, Michael and Furmaniak, Jadwiga and Rees-Smith, Bernard and Bonifacio, Ezio and Ziegler, Anette G. and Lernmark, Åke and Achenbach, Peter},
  issn         = {1935-5548},
  language     = {eng},
  number       = {6},
  pages        = {1675--1680},
  publisher    = {American Diabetes Association},
  series       = {Diabetes Care},
  title        = {GAD Autoantibody Affinity in Adult Patients With Latent Autoimmune Diabetes, the Study Participants of a GAD65 Vaccination Trial},
  url          = {http://dx.doi.org/10.2337/dc13-1719},
  volume       = {37},
  year         = {2014},
}