| 1. |
- 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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| 2. |
- 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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