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- Andersson, C, et al.
(författare)
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Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes
- 2013
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Ingår i: Pediatric Diabetes. - : Wiley-Blackwell. - 1399-543X .- 1399-5448. ; 14:2, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- Andersson C, Vaziri-Sani F, Delli AJ, Lindblad B, Carlsson A, Forsander G, Ludvigsson J, Marcus C, Samuelsson U, Ivarsson SA, Lernmark A, Elding Larsson H, the BDD Study group. Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes. Pediatric Diabetes 2013: 14: 97-105. Objective To establish the diagnostic sensitivity of and the relationships between autoantibodies to all three Zinc transporter 8 (Zinc transporter 8 autoantibody to either one, two, or all three amino acid variants at position 325, ZnT8A) variants to human leukocyte antigen (HLA)-DQ and to autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A), and insulin (IAA). Methods We analyzed 3165 patients with type 1 diabetes (T1D) in the Better Diabetes Diagnosis study for HLA-DQ genotypes and all six autoantibodies (ZnT8RA, arginine 325 Zinc transporter 8 autoantibody; ZnT8WA, tryptophan 325 Zinc transporter 8 autoantibody; ZnT8QA, glutamine 325 Zinc transporter 8 autoantibody; GADA, IA-2A, and IAA). Results ZnT8A was found in 65% of the patients and as many as 108 of 3165 (3.4%) had 13 ZnT8A alone. None had ZnT8QA alone. Together with GADA (56%), IA-2A (73%), and IAA (33%), 93% of the T1D patients were autoantibody positive. All three ZnT8A were less frequent in children below 2 yr of age (pandlt;0.0001). All three ZnT8A were associated with DQA1-B1*X-0604 (DQ6.4) and DQA1-B1*03-0302 (DQ8). ZnT8WA and ZnT8QA were negatively associated with DQA1-B1*05-02 (DQ2). Conclusions Analysis of ZnT8A increased the diagnostic sensitivity of islet autoantibodies for T1D as only 7% remained islet autoantibody negative. The association between DQ6.4 and all three ZnT8A may be related to ZnT8 antigen presentation by the DQ6.4 heterodimer.
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- Sanjeevi, Carani B., et al.
(författare)
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The risk conferred by HLA-DR and DQ for type 1 diabetes in 0-35-year age group are different in different regions of Sweden
- 2008
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. - 9781573317337 ; 1150, s. 106-11
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Tidskriftsartikel (refereegranskat)abstract
- HLA DR4-DQ8 and DR3-DQ2 haplotypes account for 89% of newly diagnosed cases of type 1 diabetes (T1D) in Sweden. The presence of a single copy of DQ6 confers protection. The aim of the present study is to evaluate whether the risk conferred by high risk HLA DR and DQ to T1D is similar in all regions of Sweden and see whether there are any significant regional differences. The subjects comprised 799 consecutively diagnosed T1D patients and 585 age-, sex-, and geography-matched healthy controls in the age group 0-35 years. HLA typing for high-risk haplotypes was previously performed using PCR-SSOP and RFLP. The results showed that HLA DR3-DR4 gave an odds ratio of 8.14 for the whole of Sweden. However, when the study group was divided into six geographical regions, subjects from Stockholm had the highest OR, followed by those from Lund, Linköping, Gothenburg, Umeå, and Uppsala. Absolute protection was conferred by the presence of DQ6 in subjects from the Linköping region, but varied in the other regions. The frequency of DR3 and DQ2, DR4 and DQ8, DR15, and DQ6 in patients showed high linkage for each region, but were different between regions. In conclusion: The risk conferred by high-risk HLA varies in different regions for a homogenous population in Sweden. The results highlight the important role played by the various environmental factors in the precipitation of T1D.
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- Sun, Chengjun, et al.
(författare)
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CRYAB-650 C>G (rs2234702) affects susceptibility to type 1 diabetes and IAA-positivity in Swedish population
- 2012
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Ingår i: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 73:7, s. 759-766
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.
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- Jonsdottir, Berglind, et al.
(författare)
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Thyroid autoimmunity in relation to islet autoantibodies and HLA-DQ genotype in newly diagnosed type 1 diabetes in children and adolescents
- 2013
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Ingår i: Diabetologia. - : Springer Verlag (Germany). - 0012-186X .- 1432-0428. ; 56:8, s. 1735-1742
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to investigate, in children newly diagnosed with type 1 diabetes: (1) the prevalence of autoantibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb); and (2) the association between TPOAb, TGAb or both, with either islet autoantibodies or HLA-DQ genes. less thanbrgreater than less thanbrgreater thanBlood samples from 2,433 children newly diagnosed with type 1 diabetes were analysed for TPOAb and TGAb in addition to autoantibodies against arginine zinc transporter 8 (ZnT8RA), tryptophan zinc transporter 8 (ZnT8WA), glutamine zinc transporter 8 (ZnT8QA), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), HLA-DQA-B1 genotypes, thyroid-stimulating hormone (TSH) and free thyroxine (T4). less thanbrgreater than less thanbrgreater thanAt type 1 diabetes diagnosis, 12% of the children had thyroid autoantibodies (60% were girls; p andlt; 0.0001). GADA was positively associated with TPOAb (p andlt; 0.001) and with TGAb (p andlt; 0.001). In addition, ZnT8A was associated with both TPOAb (p = 0.039) and TGAb (p = 0.015). DQB1*05:01 in any genotype was negatively associated with TPOAb (OR 0.55, 95% CI 0.37, 0.83, p value corrected for multiple comparisons (p (c)) = 0.012) and possibly with TGAb (OR 0.55, 95% CI 0.35, 0.87, p (c) = 0.07). Thyroid autoimmunity in children newly diagnosed with type 1 diabetes was rarely (0.45%) associated with onset of clinical thyroid disease based on TSH and free T4. less thanbrgreater than less thanbrgreater thanGADA and ZnT8A increased the risk for thyroid autoimmunity at the time of clinical diagnosis of type 1 diabetes, while HLA-DQB1*05:01 reduced the risk. However, the associations between thyroid autoimmunity and HLA-DQ genotype were weak and did not fully explain the co-occurrence of islet and thyroid autoimmunity.
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