| 1. |
- Hagopian, William A., et al.
(författare)
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Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type
- 1993
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 91:1, s. 368-374
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Tidskriftsartikel (refereegranskat)abstract
- 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 identical to native islet GAD65. Like native antigen, recombinant GAD65 migrated as two bands during electrophoresis, but converted to one under stronger reduction. Immunoprecipitation was linear with respect to antibody or antigen concentration. In 120 population-based diabetic patients of all ages grouped by treatment at onset and after 18 mo, GAD65Ab were present in 70% on insulin (n = 37), 10% on oral agent (n = 62, P < 0.0001), 69% changing from oral agent to insulin (n = 16, P < 0.001), and 1 of 33 controls. 65% with GAD65Ab, versus 8% without, changed from oral agent to insulin (P < 0.01). The GAD65Ab quantitative index was remarkably stable, and only 2 of 32 patients changed antibody status during follow-up. Concordance between GAD65Ab and islet cell antibodies was 93%. Quantitative correlation was approximate but significant. This highly sensitive, quantitative, high capacity assay for GAD65Ab reveals treatment requirements better than clinical criteria, perhaps guiding immunomodulatory therapy.
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| 2. |
- Pettersson, Anna, et al.
(författare)
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HLA genotypes in coeliac disease and healthy individuals carrying gliadin antibodies
- 1993
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Ingår i: European Journal of Gastroenterology and Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0954-691X. ; 5:6, s. 445-450
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Tidskriftsartikel (refereegranskat)abstract
- 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 compared with those from 19 gliadin antibody-positive and 96 antibody-negative healthy blood donors.Methods: Immunoglobulin G and A gliadin antibodies were measured with a micro-enzyme-linked immunosorbent assay technique. Restriction fragment length polymorphism typing for determination of HLA was carried out by means of Southern blot analysis of restriction digests.Results: Coeliac disease was significantly correlated with the presence of HLA-DR3 and DQ2, whereas DQ1, DQ7, DR1, DR4 and DR5 were all under-represented in coeliac disease patients. Of the extended haplotypes, only DR3-DQ2 was associated with the disease, while DR1-DQ1, DR4-DQ7 and DR5-DQ7 were under-represented. The correlation between DR3-DQ2 and coeliac disease depended on homozygosity; 29% of the patients and 4% of the controls were homozygous for DQ2 compared with 18 and 1%, respectively, for DR3. Only five out of 19 of the gliadin antibody-positive healthy blood donors had HLA genotypes characteristic of coeliac disease, while 15 were DQ1-positive which would be expected to confer protection.Conclusion: These findings suggest that the presence or development of gliadin antibodies is independent of the HLA genotype.
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| 3. |
- Sundkvist, Göran, et al.
(författare)
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Islet cell antibodies, but not glutamic acid decarboxylase antibodies, are decreased by plasmapheresis in patients with newly diagnosed insulin-dependent diabetes mellitus
- 1994
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 78:5, s. 1159-1165
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Tidskriftsartikel (refereegranskat)abstract
- The effects of plasmapheresis on islet autoantibody levels, C-peptide (β-cell function), and hemoglobin-A1c (HbA1c, metabolic control) were tested in a prospective blinded study of 18 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients randomly assigned to receive plasmapheresis (P), carried out as double filtration, or sham (S) treatment at diagnosis and 3 months thereafter. At diagnosis, 6 of 8 patients (75%) in group P and 9 of 10 patients (90%) in group S had islet cell antibodies (ICA), whereas 4 of 8 (50%) and 7 of 10 (70%) patients, respectively, had glutamic acid decarboxylase antibodies (GAD65-Ab), with no significant differences between the groups in ICA and GAD65-Ab levels. After 6 months, P patients showed significantly lower ICA levels than S patients (11 ± 6 and 128 ± 47 Juvenile Diabetes Foundation International Units, respectively; P < 0.02) due to an increase in ICA levels in 8 of 9 (88%) of the S patients not seen in P patients (P < 0.002). Concurrently, HbA1c stabilized in P, but not in S, patients and was significantly lower by 24 months (6.58 ± 0.54% vs. 9.76 ± 1.21%; P < 0.05). Moreover, fasting C-peptide increased significantly (214 ± 11 pmol/L; P < 0.05) over the first 6 months in P. After the initial 6 months, ICA levels tended to decrease in all patients and were not detected after 60 months. GAD65-Ab levels were not influenced by plasmapheresis and, also in contrast to ICA, increased significantly (P < 0.05) in the whole study population after 60 months. In fact, 4 initially negative patients became GAD65-Ab positive after diagnosis (in 2 patients > 24 months after diagnosis). We conclude that plasmapheresis of newly diagnosed IDDM patients does not change subsequent GAD65-Ab levels, but ICA are significantly decreased with associated improved C-peptide and HbA1c levels.
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| 4. |
- Sundkvist, Göran, et al.
(författare)
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Islet cell antibody reactivity with human fetal pancreatic islets
- 1991
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Ingår i: Diabetes Research and Clinical Practice. - 0168-8227. ; 14:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the possibility of autoimmune processes against pancreatic islets in fetal life, we tested islet cell antibody (ICA) reactivity with 14 fetal pancreata obtained after abortion at the 15th up to the 19th week of gestation. Pancreatic islets positive for a monoclonal proinsulin antibody but non-reactive with ICA negative control serum were found in 9 14 pancreata and all ( 9 9) of them showed a positive reaction with the ICA standard. It is concluded that ICA reactivity may be detected in fetal human pancreata. Further studies on fetal islet cell antibody reactivity in the development of insulin dependent diabetes mellitus (IDDM) are warranted.
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