scholarly journals Circulating anti‐glutamic acid decarboxylase‐65 antibody titers are positively associated with the capacity of insulin secretion in acute‐onset type 1 diabetes with short duration in a Japanese population

2019 ◽  
Vol 10 (6) ◽  
pp. 1480-1489
Author(s):  
So Yamamura ◽  
Tomoyasu Fukui ◽  
Yusaku Mori ◽  
Toshiyuki Hayashi ◽  
Takeshi Yamamoto ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Secretion ◽  
Glutamic Acid ◽  
Glutamic Acid Decarboxylase ◽  
Japanese Population ◽  
Acute Onset ◽  
Acid Decarboxylase ◽  
Antibody Titers ◽  
Glutamic Acid Decarboxylase 65

Immune reactivity to glutamic acid decarboxylase 65 in stiff-man syndrome and type 1 diabetes mellitus

The Lancet ◽  
2000 ◽  
Vol 356 (9223) ◽  
pp. 31-35 ◽  
Author(s):  
Tobias Lohmann ◽  
Mohammed Hawa ◽  
R David G Leslie ◽  
Russell Lane ◽  
Jean Picard ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Glutamic Acid ◽  
Type 1 Diabetes Mellitus ◽  
Glutamic Acid Decarboxylase ◽  
Acid Decarboxylase ◽  
Immune Reactivity ◽  
Stiff Man Syndrome ◽  
Glutamic Acid Decarboxylase 65

scholarly journals Humoral Autoimmunity against the Extracellular Domain of the Neuroendocrine Autoantigen IA-2 Heightens the Risk of Type 1 Diabetes

Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2528-2537 ◽  
Author(s):  
Michael P. Morran ◽  
Anna Casu ◽  
Vincent C. Arena ◽  
Susan Pietropaolo ◽  
Ying-Jian Zhang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Type 1 Diabetes ◽  
Glutamic Acid ◽  
Glutamic Acid Decarboxylase ◽  
Extracellular Domain ◽  
Full Length ◽  
Antigenic Determinants ◽  
Acid Decarboxylase ◽  
Glutamic Acid Decarboxylase 65

The objective of this study was to determine whether antigenic determinants localized within the extracellular domain of the neuroendocrine autoantigen tyrosine phosphatase-like protein IA-2 are targets of humoral responses in type 1 diabetes (T1DM). Previous studies indicated that the immunodominant region of IA-2 is localized within its intracellular domain (IA-2ic; amino acids 601–979). We analyzed 333 subjects from the Children’s Hospital of Pittsburgh study, 102 of whom progressed to insulin-requiring diabetes (prediabetics). Autoantibodies from these individuals were initially assayed for ICA512bdc (Barbara Davis Center amino acids 257–556; 630–979), IA-2ic (amino acids 601–979), and IA-2 full-length (amino acids 1–979) in addition to islet cell antibody (ICA), glutamic acid decarboxylase, 65-kDa isoform, and insulin autoantibodies. We identified an autoantibody response reactive with the extracellular domain of IA-2 that is associated with very high risk of T1DM progression. Relatives with no detectable autoantibodies against ICA512bdc (or IA-2ic) exhibited antibody responses against the IA-2 full-length peptide (log rank, P = 0.008). This effect was also observed in first-degree relatives who were positive for glutamic acid decarboxylase, 65–kDa isoform (log rank, P = 0.026) or at least two islet autoantibodies but were negative for ICA512bdc (log rank, P = 0.022). Competitive binding experiments and immunoprecipitation of the IA-2 extracellular domain (amino acid residues 26–577) further lend support for the presence of autoantibodies reactive with new antigenic determinants within the extracellular domain of IA-2. In summary, the addition of measurements of autoantibodies reactive with the IA-2 extracellular domain to assays geared to assess the progression of autoimmunity to clinical T1DM may more accurately characterize this risk. This has considerable implications not only for stratifying high diabetes risk but also facilitating the search for pathogenic epitopes to enable the design of peptide-based immunotherapies that may prevent the progression to overt T1DM at its preclinical stages.

scholarly journals Danish children born with glutamic acid decarboxylase-65 and islet antigen-2 autoantibodies at birth had an increased risk to develop type 1 diabetes

2011 ◽  
Vol 164 (2) ◽  
pp. 247-252 ◽  
Author(s):  
Stefanie Eising ◽  
Anita Nilsson ◽  
Bendix Carstensen ◽  
David M Hougaard ◽  
Bent Nørgaard-Pedersen ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glutamic Acid ◽  
Glutamic Acid Decarboxylase ◽  
Case Control ◽  
Acid Decarboxylase ◽  
Increased Risk ◽  
Parental Diabetes ◽  
Glutamic Acid Decarboxylase 65 ◽  
Islet Antigen

ObjectiveA large, population-based case–control cohort was used to test the hypothesis that glutamic acid decarboxylase-65 (GAD65) and islet antigen-2 autoantibodies (IA-2A) at birth predict type 1 diabetes.Design and methodsThe design was an individually matched case–control study of all Danish type 1 diabetes patients born between 1981 and 2002 and diagnosed before May 1 2004 (median age at diagnosis was 8.8 years). Dried blood spot samples collected 5 days after birth in the 1981–2002 birth cohorts and stored at −25 °C were identified from 2023 patients and from two matched controls (n=4042). Birth data and information on parental age and diabetes were obtained from Danish registers. GAD65A and IA-2A were determined in a radiobinding assay. HLA-DQB1 alleles were analyzed by PCR using time-resolved fluorescence.ResultsGAD65A and IA-2A were found in 70/2023 (3.5%) patients compared to 21/4042 (0.5%) controls resulting in a hazard ratio (HR) of 7.49 (P<0.0001). The HR decreased to 4.55 but remained significant (P<0.0003) after controlling for parental diabetes and HLA-DQB1 alleles. Conditional logistic regression analysis showed a HR of 2.55 (P<0.0001) for every tenfold increase in the levels of GAD65A and IA-2A. This HR decreased to 1.93 but remained significant (P<0.001) after controlling for parental diabetes and HLA-DQB1 alleles.ConclusionThese data suggest that GAD65A and IA-2A positivity at birth are associated with an increased risk of developing type 1 diabetes in Danish children diagnosed between 1981 and 2004.

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