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Glutamic acid decarboxylase autoantibodies may aid in rapid screening strategies predicting IDDM before clinical onset. Rat islets contain GAD65 and GAD67 autoantibody targets, but human islets express only GAD65, now confirmed by direct immunoprecipitation from radiolabeled rat and human islets. Because human IDDM involves β-cell-specific autoimmunity, we tested 190 new IDDM patients and 51 healt
Abstract: Mexican American patients (n = 35) with insulin‐dependent diabetes mellitus (IDDM) and control subjects (n = 39) were HLA‐DQA and DQB typed by the polymerase chain reaction technique combined with allele‐specific oligonucleotide probes. Either DQBl*0302 or DQB1*0201 was present among 91% (32/35) of the patients compared to 67% (26/39) of controls. Either DQA1*0501 or DQA1*0301 was prese
The association between HLA-DR and -DQ and insulin-dependent diabetes mellitus (IDDM) in a defined high-incidence area was analyzed in a total of 58 population-based patients, representing 77% of IDDM patients with age at onset below 16 years, and in 92 unrelated parents in control families without IDDM. HLA haplotypes were confirmed by analyzing first-degree relatives in both groups. Seven differ
Abstract. Two unrelated young males with the unusual simultaneous presence of insulin‐dependent diabetes mellitus, ulcerative colitis and primary sclerosing cholangitis are reported. Both patients manifested homozygosity for the DR3‐DQw2 (DQB*0201) HLA genotypes. We believe that homozygosity for this genotype may predispose for this type of multi‐organ autoimmune disease. 1993 Blackwell Publishin
At and before onset, most insulin-dependent diabetics (IDDM) have islet GAD65 autoantibodies (GAD65Ab). Since IDDM also occurs in older patients where non-insulin-dependent diabetes is common, we studied GAD65Ab at onset to classify diabetes type. Our quantitative immunoprecipitation assay uses recombinant human islet GAD65 stably expressed in hamster fibroblasts. Electrophoretic mobility was iden
A study of 109 Swedish patients and 85 healthy Swedish controls with Crohn's disease (CD) by HLA class II RFLP genotyping was carried out. There was no significant association for any single DR or DQ specificity or phenotypic combination of DR and/or DO specificities among our study group of Caucasian extraction.
Inbred specific pathogen-free diabetes-prone (DP) and diabetes-resistant (DR) BB rats were crossed to produce F1 and intercrossed to produce F2 rats. Diabetes segregates in these crosses as a recessive trait on rat chromosome 4. The weight gain of genetically diabetes-prone rats born to F1 healthy parents was studied to avoid effects of maternal diabetes. The weight gain of the F2 rats was initial
Glutamic acid decarboxylase (GAD) catalyzes the synthesis of γ-aminobutyric acid (GABA), which is known as a major inhibitory neurotransmitter in the central nervous system (CNS), but is also present outside the CNS. Recent studies showed that GAD is the major target of autoantibodies associated with the development of insulin-dependent diabetes mellitus and of the rare stiff man syndrome. Studies
Objective: Coeliac disease is closely associated with the presence of gliadin antibodies and certain HLA class II alleles. The aim of this study was to compare the HLA genotype in gliadin antibody-positive individuals without coeliac disease with that in patients with clinically verified coeliac disease.Design: HLA genotyping was carried out in 65 patients with coeliac disease and the results were
OBJECTIVE - To determine the effects of islet cell antibodies on β-cell function during the first 3 yr after diagnosis in type II diabetic patients. RESEARCH DESIGN AND METHODS - β-cell function in type II diabetic patients with (n = 11, 50 ± 5 yr of age) and without (n = 10, 52 ± 4 yr of age) ICA was followed prospectively and compared with β-cell function in type I adult diabetic patients (n = 1
Islet cell antibodies (ICA), fasting plasma C-peptide, and HbA(1c) were evaluated up to 10 years after diagnosis in 52 patients with diabetes diagnosed in adult age (mean age at diagnosis 53 ± 2 yr, range 21-76 yr) with a high (>20 IU/day) insulin requirement (group A) and in 50 matched control patients with diabetes diagnosed in adult age (mean age at diagnosis 54 ± 2 yr, range 24-73 yr) with low
The BB rat is among the best models of insulin−dependent diabetes mellitus — with onset and pathogenesis closely resembling the human disease. One unusual feature is a severe T−cell lymphopenia, which appears to be inherited as a recessive trait controlled by a single gene, Lyp. Based on genetic analysis of several crosses, we show that development of diabetes involves at least three genes: Lyp, w
A novel sequential Injection Immunoassay (SI I A) method Is described which utilizes Immunomagnetic beads to Investigate short-time antibody binding. The method Is versatile and flexible and may therefore be adapted to many different applications. Initial results for a competitive assay are also presented. The Immunomagnetic bead reactor Is created within the flowing stream by retaining Immunomagn
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The effect of age on ICA and thyrogastric antibodies at diagnosis of IDDM was evaluated in 633 consecutively diagnosed Swedish diabetic patients aged 15-34 yr and in 282 volunteers of the same age. ICAs were present in 61% (383 of 633) of the patients and in 2% (5 of 282) of control subjects. When the initial classification was considered, ICAs were detected in 69% (327 of 473) of patients with ID
GAD is an autoantigen in IDDM. Molecular cloning and specific antibodies allowed us to demonstrate that only the lower Mr GAD64 isoform is expressed in human islets, in contrast to human brain, rat islets, and rat brain, all of which express both GA064 and GAD67. Expression of the human islet GAD64 isoform in COS-7 and BHK cells resulted in an enzymatically active rGAD64, which is immunoreactive w
Previous studies have determined that daily low dose injections of the potent cytokine interleukin-1β (IL-1β) decreased the frequency of insulin-dependent diabetes mellitus (IDDM) in diabetes-prone (DP) BB rats. In contrast, high dose injections induced an earlier than normal onset. In this study we tested whether the effects of daily human recombinant IL-1β injections on leukocyte subsets were as
The goal of the Fourth International Workshop for Standardization of ICA Measurements was to determine the specificity of ICA assays and their ability to distinguish between control sera (n = 57) and sera from IDDM-related individuals-representing relatives of IDDM patients (n = 21), healthy individuals who later developed IDDM (n = 8), or newly diagnosed IDDM patients (n = 23). Results from 28 la
