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OBJECTIVE - To investigate the association of GAD (65-kDa) autoantibodies (GAD65-Abs) and IA-2 autoantibodies (IA-2-Abs) with human leukocyte antigen (HLA)-DQ and insulin gene (INS) risk markers in patients with recent-onset IDDM and their siblings. RESEARCH DESIGN AND METHODS - Blood was sampled from 608 recent-onset IDDM patients and 480 siblings, aged 0-39 years and consecutively recruited by t
Most IDDM patients temporarily restore some of their beta-cell function following the initiation of insulin therapy. The aim of this study was to analyse the influence of age, gender, metabolic state at diagnosis and presence of autoantibodies (GAD65 antibodies and ICA) on the duration of the clinical partial remission. In total, 149 consecutively diagnosed IDDM children, 0-16 y old (70F, 79M, mea
Autoantibodies to glutamic acid decarboxylase (GAD65Ab) are common in both caucasian and Japanese patients with insulin-dependent diabetes mellitus (type 1), while the type 1-associated HLA haplotypes differ. In the present study, we analyzed GAD65Ab in relation to HLA-DQ and -DR alleles in Japanese type 1 patients. GAD65Ab were found in 58% short-duration (less than 5 years) type 1, 23% long-dura
Two large population-based case-control studies are reviewed. The aim is to determine the effects of HLA, other genetic factors and immune markers (ICA, IAA and GAD65Ab) on the age at onset of insulin-dependent diabetes mellitus (IDDM) in 0-34 year olds. The primary HLA risk gene sequence for IDDM was difficult to identify because of the low recombination frequency within the HLA region. The frequ
The identification of class II binding peptide epitopes from autoimmune disease-related antigens is an essential step in the development of antigen- specific immune modulation therapy. In the case of type 1 diabetes, T cell and B cell reactivity to the autoantigen glutamic acid decarboxylase 65 (GAD65) is associated with disease development in humans and in nonobese diabetic (NOD) mice. In this st
Islet cell antibodies (ICA), autoantibodies to glutamic acid decarboxylase (GAD) and HLA genotypes were examined in 31 patients with diabetes and a mitochondria! gene mutation located at base pair 3243 (mtDNA 3243 mutation). ICA was detected in 42 % (13/31) of these patients compared to 0 of 90 among healthy control subjects. The ICA showed a "non-restricted" pattern of staining in all 13 ICA-posi
Objectives. To study the frequency of islet cell (ICA) and glutamic acid decarboxylase (GAD-Ab) antibodies in patients with hyperthyroidism of different types at diagnosis before treatment and in the euthyroid state following treatment. Setting. Department of Endocrinology, Malmo University Hospital, Malmo, Sweden. Subjects and design. Blood samples were collected at diagnosis from 129 hyperthyroi
Insulin dependent diabetes mellitus (IDDM) is linked to HLA factors on human chromosome 6 and strongly associated with the presence of autoantibodies against the glutamic acid decarboxylase isoform GAD65. These autoantibodies, GAD65Ab are detected both before and at the time of clinical diagnosis. Molecular sequencing of HLA alleles and PCR-based genotyping have improved our understanding of the l
To evaluate the association of autoimmunity to glutamic acid decarboxylase (GAD) with insulin-dependent diabetes mellitus (IDDM) and IDDM-associated human leukocyte antigen (HLA) types, we studied a unique group of 47 patients with autoimmune polyendocrine syndrome type 1, a recessive disease not associated with HLA. GAD65 antibodies (GAD65-Ab), GAD67-Ab, islet cell antibodies, and HLA-DQA1, -DQB1
The aim of this study was to determine the association between childhood insulin-dependent diabetes mellitus (IDDM) and HLA-DR4 subtypes and to test in a population-based investigation whether the DR4 association has an effect independent to that of DQ. First, HLA genotyping identified DR4 in 337/425 (79%) patients and 148/367 (40%) controls (Odds Ratio 5.67; p < 0.01). Second, a total of 14 DR4 s
The association between HLA-DQ haplotypes and insulin-dependent diabetes mellitus (IDDM) was studied in 48 children from 44 families ascertained from the high incidence area around Umea, Sweden. Numerous hypotheses have been proposed to explain associations between HLA and IDDM, but comparisons of statistical models based on these hypotheses have not been attempted. The aim of the present study wa
To analyze whether HLA may be a determinant of the risk of developing cervical cancer precursor lesions, the association between HLA and cervical neoplasia among HPV16-seropositive and -negative subjects was determined in a population-based cohort in the Vasterbotten county of Northern Sweden. HLA genotyping of DR and DQ was done by PCR in 74 patients and 164 healthy controls matched for age, sex
The prevalence and titre of epitope-specific autoantibodies to glutamic acid decarboxylase (GAD65) in 155 insulin-dependent diabetic (IDDM) and 9 GAD65 antibody (Ab)-positive healthy children were determined using four GAD65/67 chimaeric molecules which discriminate among the N-terminal (N), middle (M) and C-terminal (C) epitopes of GAD65. Radioligand binding assays for IgG Ab used immunoprecipita
Glutamic acid decarboxylase (GAD) enzymes catalyse the formation of gamma-aminobuturic acid (GABA), which is a major transmittor in the central nervous system but also exerts functions in peripheral organs. Recent molecular analyses have revealed surprising new roles for the GAD isoforms in human diseases of autoimmune character including neurological disorders and insulin-dependent diabetes. In t
It was recently reported that antibodies against glutamic acid decarboxylase (GADAb) have a high positive predictive value for insulin-dependency in non-insulin-dependent diabetic (NIDDM) patients. We studied 289 patients classified at onset as having NIDDM. Patients positive for GAD65Ab had a disease onset at a younger age, lower body mass index (BMI) and lower serum C-peptide concentration, and
