| 1. |
- Kanatsuna, N, et al.
(författare)
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Doubly reactive INS-IGF2 autoantibodies in children with newly diagnosed autoimmune (type 1) diabetes
- 2015
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Ingår i: Scandinavian Journal of Immunology. - : Wiley-Blackwell. - 0300-9475 .- 1365-3083. ; 82:4, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim of this study was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ or both, in patients and controls with newly diagnosed type 1 diabetes. Patients (n = 676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n = 363) were analysed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, ZnT8QA and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than in controls (P < 0.001). Irrespective of age at diagnosis, 19% (126/676) of the patients had INS-IGF2A when the cut-off was the 95th percentile of the controls (P < 0.001). The risk of INS-IGF2A was increased among HLA-DQ2/8 (OR = 1.509; 95th CI 1.011, 2.252; P = 0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans-heterodimers, rather than cis-heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes.
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| 2. |
- Hall, T. R., et al.
(författare)
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Longitudinal epitope analysis of insulin-binding antibodies in type 1 diabetes
- 2006
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 146:1, s. 41531-41531
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Tidskriftsartikel (refereegranskat)abstract
- Autoantibodies to insulin (IAA) are one of the first markers of the autoimmune process leading to type 1 diabetes (T1D). While other autoantibodies in T1D have been studied extensively, relatively little is known about IAA and their binding specificities, especially after insulin treatment is initiated. We hypothesize that insulin antibodies (IA) that develop upon initiation of insulin treatment differ in their epitope specificities from IAA. We analysed insulin antibody binding specificities in longitudinal samples of T1D patients (n = 49). Samples were taken at clinical diagnosis of disease and after insulin treatment was initiated. The epitope specificities were analysed using recombinant Fab (rFab) derived from insulin-specific monoclonal antibodies AE9D6 and CG7C7. Binding of radiolabelled insulin by samples taken at onset of the disease was significantly reduced in the presence of rFab CG7C7 and AE9D6. rFab AE9D6 competed sera binding to insulin significantly better than rFab CG7C7 (P = 0.02). Binding to the AE9D6-defined epitope in the initial sample was correlated inversely with age at onset (P = 0.005). The binding to the AE9D6-defined epitope increased significantly (P < 0.0001) after 3 months of insulin treatment. Binding to the CG7C7-defined epitope did not change during the analysed period of 12 months. We conclude that epitopes recognized by insulin binding antibodies can be identified using monoclonal insulin-specific rFab as competitors. Using this approach we observed that insulin treatment is accompanied by a change in epitope specificities in the emerging IA.
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| 3. |
- Padoa, C J, et al.
(författare)
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Epitope analysis of insulin autoantibodies using recombinant Fab
- 2005
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 140:3, s. 564-571
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Tidskriftsartikel (refereegranskat)abstract
- Autoantibodies to insulin are often the first autoantibodies detected in young children with type 1 diabetes and can be present before the onset of clinical diabetes. These autoantibodies and their epitopes are, however, not well characterized. We explored the use of monoclonal antibodies and their recombinant Fab as reagents for epitope analysis. In this study we cloned and characterized the recombinant Fab of the insulin-specific monoclonal antibody CG7C7. We found the epitope of this antibody to be located predominantly at the A-chain loop of the insulin molecule. The recombinant Fab was then used to compete for insulin binding against insulin autoantibodies present in sera from patients with type 1 or type 1.5 diabetes. In competition experiments with sera positive for autoantibodies to insulin the recombinant Fab significantly reduced the binding to [I-125]-insulin by sera of type 1 (n = 35) and type 1.5 diabetes [latent autoimmune diabetes in adults (LADA)] (n = 14) patients (P < 0.0001). We conclude that competition between insulin-specific monoclonal antibodies or their recombinant Fab and insulin autoantibodies should prove useful in the epitope analysis of autoantibodies to insulin.
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| 4. |
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| 5. |
- Fawwaz, S., et al.
(författare)
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No evidence of association of the PDCD1 gene with Type 1 diabetes
- 2007
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 24:12, s. 1473-1477
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To test the association between the immunoreceptor PD-1 (PDCD1) gene and Type 1 diabetes mellitus (T1DM). This gene has been reported to be associated with other autoimmune diseases such as systemic lupus erythematosus (SLE) as well as T1DM. Methods: Genotyping of single nucleotide polymorphisms (SNPs) in the PDCD1 gene was performed using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP), pyrosequencing and TaqMan in two separate cohorts of Swedish patients and control subjects: a family study consisting of 184 multiplex and eight simplex families and a case-control study consisting of 586 patients and 836 control subjects. Three SNPs were genotyped: PD-1 7146, PD-1 7785 and PD-1 8738. Results: We did not detect any association or linkage between SNPs in PDCD1 and T1DM. We further performed a meta-analysis for association of PD-1 7146, PD-1 7785 and PD-1 8738 to T1DM. We detected heterogeneity in association with weak evidence for overall association. Conclusions: We conclude that PDCD1 is unlikely to be a major susceptibility gene for T1DM.
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| 6. |
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| 7. |
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| 8. |
- Thunander, Maria, et al.
(författare)
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Incidence of type 1 and type 2 diabetes in adults and children in Kronoberg, Sweden.
- 2008
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 82, s. 247-255
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Tidskriftsartikel (refereegranskat)abstract
- All newly diagnosed diabetes in Kronoberg during 3 years was registered, with blood samples from 1630/1666 (97.8%) adults. Those positive for GADab and/or ICA and/or C-peptide<0.25nmol/L (0.7%) were classified as type 1 diabetes, the remaining as type 2. Incidence of type 1 in 0-19-year-olds was 37.8(36.1-39.6, 95%CI) and in 20-100 year-olds 27.1(25.6-27.4) per 100 000 and year, it was bimodal with equal peaks in 0-9 year-olds and in 50-80-year-olds. Adults had type 2 incidence 378 (375-380), children 3.1 (2.6-3.6). Among adults 6.9% had type 1 and 93.1% type 2. Among antibodypositive adults (n=101), GADab were present in 90%, ICA in 71%, both GADab and ICA in 61%. Ophthalmology contact as second source was confirmed for 98%. There were no gender differences in type 1 in any age group, small ones in pediatric subgroups. In type 2 men predominated in ages above 40 years. Incidences of type 1 diabetes in both children and adults were very high and as high above age 50 years as in children. Incidence of type 2 was the highest reported from Sweden, to which new diagnostic criteria, a high degree of case-finding, and many elders, may have contributed, but results may also reflect a true increase in incidence of both types of diabetes.
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| 9. |
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| 10. |
- Törn, Carina, et al.
(författare)
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Increased autoantibodies to SOX13 in Swedish patients with type 1 diabetes.
- 2002
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 958, s. 218-223
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Tidskriftsartikel (refereegranskat)abstract
- This article aims to estimate the prevalence of SOX13 antibodies in Swedish patients with type 1 diabetes and healthy controls. The patients (n = 102; median age 35 years [range, 9-89]) were newly diagnosed with type 1 diabetes in a defined area in southern Sweden during 1995-1998. Islet cell antibodies (ICA) were analyzed with immunofluorescence, while glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase antibodies (IA-2A), and antibodies against the transcription factor SOX13 (SOX13Ab) were analyzed with radioimmunoprecipitating assays. SOX13Ab were found in 9.8% (10/102) of type 1 patients compared to 2.0% (2/99) in healthy controls (P = 0.033). At least one of the four autoantibodies (ICA, GADA, IA-2A or SOX13Ab) were identified in 67% (68/102) of the patients. Samples positive for IA-2A were only in one case positive also for SOX13Ab. IA-2A-positive patients were often positive also for ICA and GADA (19/27), and the same combination was also common for SOX13Ab-positive patients (6/10). Only 2.0% (2/102) were positive for SOX13Ab alone. ICA, GADA and IA-2A were more frequent in younger patients (
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