| 31. |
- Olsson, M. Landin, et al.
(författare)
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Prolonged incubation in the two-colour immunofluorescence test increases the prevalence and titres of islet cell antibodies in Type 1 (insulin-dependent) diabetes mellitus
- 1987
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Ingår i: Diabetologia. - 0012-186X. ; 30:5, s. 327-332
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Tidskriftsartikel (refereegranskat)abstract
- The conventional indirect immunofluorescence test of islet cell antibodies was recently improved by the development of a two-colour immunofluorescence assay using a monoclonal proinsulin antibody to detect islet B cells. The aim of this study was to test whether in this new assay the prevalence and titre of ICA were affected by the time of incubation carried out in the presence of aprotinin (Trasylol) as an inhibitor of proteolysis. The end-point titre of ICA was therefore determined in sera from 70 children aged 0.6 to 15 years with recent onset Type 1 (insulin-dependent) diabetes mellitus, 50 healthy control subjects and 97 non-diabetic siblings of Type 1 diabetic children. In the conventional twocolour assay, ICA was positive in 53/70 (76%) Type 1 diabetic patients, 1/50 control subjects and 2/97 siblings after 30 min incubation. Prolonged incubation for 18 h increased the prevalence of ICA positive samples to 62/70 (89%) in the diabetic patients and to 2/50 in the control subjects, while the prevalence among the siblings was unchanged. Of the ICA positive non-diabetic subjects, one control child has a father with Type 1 diabetes, and one of the siblings subsequently developed Type 1 diabetes. In the diabetic patients the median titre was 1:32 for the 30 min incubation, and it increased to 1:64 for the 18 h incubation (p<0.001). A marked prozone effect was seen; 16% of the samples from the Type 1 diabetic children sera were negative at a 1:2 dilution, but were found positive at higher dilutions. In conclusion, an 18 h incubation increases the end point titres and the prevalence of ICA in the two-colour ICA assay in Type 1 diabetic children of recent onset. The prevalence and levels of ICA among these patients may be larger than hitherto expected.
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| 32. |
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| 33. |
- Sairenji, T., et al.
(författare)
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Relating homology between the Epstein-Barr virus BOLF1 molecule and HLA-DQw8 β chain to recent onset Type 1 (insulin-dependent) diabetes mellitus
- 1991
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Ingår i: Diabetologia. - 0012-186X. ; 34:1, s. 33-39
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Tidskriftsartikel (refereegranskat)abstract
- A role for the Epstein-Barr virus in initiating Type 1 (insulin-dependent) diabetes mellitus has been proposed since Epstein-Barr virus BOLF1(497-513) AVTPL RIFIVP PAAEY has an 11 amino acid identity with HLA-DQw8 β (49-60) AVTPL GPPAAEY. Rabbit antisera to the BOLF1 (496-515) peptide crossreacted with the homologous DQw8 β (44-63) peptide but not with the related DQw7 β(44-63) peptide, which differed from the DQw8 peptide only in an ALA to ASP substitution in position 57. Antisera to DQw8 β(49-60) reacted with the DQw8 β(44-63) peptide and BOLF1 (496-515), but not with DQw7 β (44-63). The antiserum to the BOLF1 peptide bound to denatured class II major histocompatibility complex β chains from Epstein-Barr virus-transformed DQw8-positive lymphocytes in an immunoblotting analysis. Epstein-Barr virus antibodies were detected at equal frequencies and similar titres in sera of 30 patients with Type 1 diabetes (16 of 30;63%) and in sera of 20 non-diabetic control subjects (13 of 20;65%). Sera from diabetic patients did not bind to DQw8 β (44-63) or BOLF1(496-515) peptides. From these data we conclude that there is no simple relationship between serological evidence of Epstein-Barr virus infection and crossreactions between homologous Epstein-Barr virus and class II major histocompatibility complex peptides.
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| 34. |
- Sanjeevi, C. B., et al.
(författare)
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Association between autoantibody markers and subtypes of DR4 and DR4-DQ in Swedish children with insulin-dependent diabetes reveals closer association of tyrosine pyrophosphatase autoimmunity with DR4 than DQ8
- 1998
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Ingår i: Tissue Antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 51:3, s. 281-286
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Tidskriftsartikel (refereegranskat)abstract
- HLA DQA1(*)0301-DQB1(*)0302 (DQ8) and DQA1(*)0501-DQB1(*)0201 (DQ2) are positively and DQA1(*)0102-DQB1(*)0602 (DQ6) negatively associated with IDDM. In DQA1(*)0301-DQB1(*)0302 (DQ8)-positive patients, susceptibility is also mediated by DRB1(*)0401. The aim of the study was to determine the association between HLA-DR4 and DQ and the presence of GAD65, ICA512, and insulin autoantibodies as well as ICA in 425 Swedish children with IDDM and 367 controls in the age group of 0-15 years. We found that ICA512 autoantibodies were associated primarily with DRB1(*)0401 and not with DQA1(*)0301-DQB1(*)0302 (DQ8). No such hierarchy could be demonstrated for insulin autoantibodies, which were associated with both DQA1(*)0301-DQB1(*)0302 (DQ8) and DRB1(*)0401. GAD65 autoantibodies, known to be closely associated with DQA1(*)0501-DQB1(*)0201 (DQ2)-DRB1(*)0301 haplotype, also showed no preferential association with DQA1(*)0301-DQB1(*)0302 (DQ8) versus DRB1(*)04. These results suggest that the immune response to different β-cell autoantigens may be mediated via HLA class II molecules from different loci. Design of the antigen-specific immuno-intervention trials should take into account these HLA-DR and DQ subtype associations.
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| 35. |
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| 36. |
- Törn, C., et al.
(författare)
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Prognostic factors for the course of beta cell function in autoimmune diabetes
- 2000
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 85:12, s. 4619-4623
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Tidskriftsartikel (refereegranskat)abstract
- This study presents a 2-yr follow-up of 281 patients, aged 15-34 yr, diagnosed with diabetes between 1992 and 1993. At diagnosis, 224 (80%) patients were positive for at least one of the following autoantibodies: islet cell antibodies (ICAs), glutamic acid decarboxylase antibodies (GADAs), or tyrosine phosphatase antibodies (IA-2As), the remaining 57 (20%) patients were negative for all three autoantibodies. At diagnosis, C-peptide levels were lower (0.27, 0.16-0.40 nmol/L) in autoantibody-positive patients compared with autoantibody-negative patients (0.51, 0.28-0.78 nmol/L, P < 0.001). After 2 yr, C-peptide levels had decreased significantly in patients with autoimmune diabetes (0.20, 0.10-0.37 nmol/L, P = 0.0018), but not in autoantibody-negative patients. In patients with autoimmune diabetes, a low initial level of C-peptide (odds ratio, 2.6, 95% confidence interval, 1.7-4.0) and a high level of GADAs (odds ratio, 2.5, 95% confidence interval, 1.1-5.7) were risk factors for a C-peptide level below the reference level of 0.25 nmol/L 2 yr after diagnosis. Body mass index had a significant effect in the multivariate analysis only when initial C-peptide was not considered. Factors such as age, gender, levels of ICA or IA-2A or insulin autoantibodies (analyzed in a subset of 180 patients) had no effect on the decrease in ▀-cell function. It is concluded that the absence of pancreatic islet autoantibodies at diagnosis were highly predictive for a maintained ▀-cell function during the 2 yr after diagnosis, whereas high levels of GADA indicated a course of decreased ▀-cell function with low levels of C-peptide. In autoimmune diabetes, an initial low level of C-peptide was a strong risk factor for a decrease in ▀-cell function and conversely high C-peptide levels were protective. Other factors such as age, gender, body mass index, levels of ICA, IA-2A or IAA had no prognostic importance.
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| 37. |
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| 38. |
- Wassmuth, R., et al.
(författare)
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HLA DR AND DQ RFLP ANALYSIS IN CROHN'S DISEASE
- 1993
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Ingår i: International Journal of Immunogenetics. - 1744-3121. ; 20:5, s. 429-433
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 39. |
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