Antti-Mathias Taka, Taina Härkönen, Paula Vähäsalo, Tommi Vatanen, Johanna Lempainen, Riitta Veijola, Maaret Turtinen, Jorma Ilonen, Mikael Knip, the Finnish Pediatric Diabetes Register
{"title":"携带保护性 HLA-DQB1*06:02 等位基因的 1 型糖尿病患者的特征","authors":"Antti-Mathias Taka, Taina Härkönen, Paula Vähäsalo, Tommi Vatanen, Johanna Lempainen, Riitta Veijola, Maaret Turtinen, Jorma Ilonen, Mikael Knip, the Finnish Pediatric Diabetes Register","doi":"10.1111/tan.15720","DOIUrl":null,"url":null,"abstract":"<p>We set out to examine in an observational study characteristics of type 1 diabetes at the time of diagnosis among paediatric patients carrying the protective HLA class II <i>DQB1*06:02</i> allele. We compared characteristics of type 1 diabetes among 5530 Finnish children aged 0–14 years diagnosed between 2003 and 2018. Seventy-five children with type 1 diabetes carried the <i>DQB1*06:02</i> allele. The carriers of <i>DQB1*06:02</i> allele were compared to all children with type 1 diabetes without this allele and those with a high-risk genotype. We also analysed, how does the genotype of a high-risk haplotype paired with <i>DQB1*06:02</i> affect the phenotype of patients with newly diagnosed type 1 diabetes. Carriers of the <i>DQB1*06:02</i> allele were diagnosed at an older age than those with any other HLA class II genotype (<i>p</i> = 0.003) or the high-risk genotype (<i>p</i> < 0.001). After adjusting the results for age and sex, no significant differences in clinical markers were observed. Glutamic acid decarboxylase autoantibody (GADA) levels were higher among carriers of <i>DQB1*06:02</i> when compared to those with other genotypes (<i>p</i> = 0.033). Having a high-risk haplotype paired with <i>DQB1*06:02</i>-positive haplotype was associated with higher levels of islet antigen 2 autoantibodies (IA-2A) (<i>p</i> < 0.001) and somewhat shorter duration of symptoms (<i>p</i> = 0.043). The association between the protective <i>DQB1*06:02</i> allele and an older age at diagnosis as well as higher levels of GADA at diagnosis of type 1 diabetes was confirmed. The effects of the <i>DQB1*06:02</i>-positive haplotype seem to dominate when paired with a high-risk haplotype.</p>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"104 5","pages":""},"PeriodicalIF":5.9000,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tan.15720","citationCount":"0","resultStr":"{\"title\":\"Characteristics of Type 1 Diabetes Among Patients Carrying the Protective HLA-DQB1*06:02 Allele\",\"authors\":\"Antti-Mathias Taka, Taina Härkönen, Paula Vähäsalo, Tommi Vatanen, Johanna Lempainen, Riitta Veijola, Maaret Turtinen, Jorma Ilonen, Mikael Knip, the Finnish Pediatric Diabetes Register\",\"doi\":\"10.1111/tan.15720\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>We set out to examine in an observational study characteristics of type 1 diabetes at the time of diagnosis among paediatric patients carrying the protective HLA class II <i>DQB1*06:02</i> allele. We compared characteristics of type 1 diabetes among 5530 Finnish children aged 0–14 years diagnosed between 2003 and 2018. Seventy-five children with type 1 diabetes carried the <i>DQB1*06:02</i> allele. The carriers of <i>DQB1*06:02</i> allele were compared to all children with type 1 diabetes without this allele and those with a high-risk genotype. We also analysed, how does the genotype of a high-risk haplotype paired with <i>DQB1*06:02</i> affect the phenotype of patients with newly diagnosed type 1 diabetes. Carriers of the <i>DQB1*06:02</i> allele were diagnosed at an older age than those with any other HLA class II genotype (<i>p</i> = 0.003) or the high-risk genotype (<i>p</i> < 0.001). After adjusting the results for age and sex, no significant differences in clinical markers were observed. Glutamic acid decarboxylase autoantibody (GADA) levels were higher among carriers of <i>DQB1*06:02</i> when compared to those with other genotypes (<i>p</i> = 0.033). Having a high-risk haplotype paired with <i>DQB1*06:02</i>-positive haplotype was associated with higher levels of islet antigen 2 autoantibodies (IA-2A) (<i>p</i> < 0.001) and somewhat shorter duration of symptoms (<i>p</i> = 0.043). The association between the protective <i>DQB1*06:02</i> allele and an older age at diagnosis as well as higher levels of GADA at diagnosis of type 1 diabetes was confirmed. The effects of the <i>DQB1*06:02</i>-positive haplotype seem to dominate when paired with a high-risk haplotype.</p>\",\"PeriodicalId\":13172,\"journal\":{\"name\":\"HLA\",\"volume\":\"104 5\",\"pages\":\"\"},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2024-11-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tan.15720\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"HLA\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/tan.15720\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"HLA","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/tan.15720","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Characteristics of Type 1 Diabetes Among Patients Carrying the Protective HLA-DQB1*06:02 Allele
We set out to examine in an observational study characteristics of type 1 diabetes at the time of diagnosis among paediatric patients carrying the protective HLA class II DQB1*06:02 allele. We compared characteristics of type 1 diabetes among 5530 Finnish children aged 0–14 years diagnosed between 2003 and 2018. Seventy-five children with type 1 diabetes carried the DQB1*06:02 allele. The carriers of DQB1*06:02 allele were compared to all children with type 1 diabetes without this allele and those with a high-risk genotype. We also analysed, how does the genotype of a high-risk haplotype paired with DQB1*06:02 affect the phenotype of patients with newly diagnosed type 1 diabetes. Carriers of the DQB1*06:02 allele were diagnosed at an older age than those with any other HLA class II genotype (p = 0.003) or the high-risk genotype (p < 0.001). After adjusting the results for age and sex, no significant differences in clinical markers were observed. Glutamic acid decarboxylase autoantibody (GADA) levels were higher among carriers of DQB1*06:02 when compared to those with other genotypes (p = 0.033). Having a high-risk haplotype paired with DQB1*06:02-positive haplotype was associated with higher levels of islet antigen 2 autoantibodies (IA-2A) (p < 0.001) and somewhat shorter duration of symptoms (p = 0.043). The association between the protective DQB1*06:02 allele and an older age at diagnosis as well as higher levels of GADA at diagnosis of type 1 diabetes was confirmed. The effects of the DQB1*06:02-positive haplotype seem to dominate when paired with a high-risk haplotype.
期刊介绍:
HLA, the journal, publishes articles on various aspects of immunogenetics. These include the immunogenetics of cell surface antigens, the ontogeny and phylogeny of the immune system, the immunogenetics of cell interactions, the functional aspects of cell surface molecules and their natural ligands, and the role of tissue antigens in immune reactions. Additionally, the journal covers experimental and clinical transplantation, the relationships between normal tissue antigens and tumor-associated antigens, the genetic control of immune response and disease susceptibility, and the biochemistry and molecular biology of alloantigens and leukocyte differentiation. Manuscripts on molecules expressed on lymphoid cells, myeloid cells, platelets, and non-lineage-restricted antigens are welcomed. Lastly, the journal focuses on the immunogenetics of histocompatibility antigens in both humans and experimental animals, including their tissue distribution, regulation, and expression in normal and malignant cells, as well as the use of antigens as markers for disease.