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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1427349
This article is part of the Research Topic Autoimmune Diseases in Childhood View all 20 articles

Next-Generation Sequencing reveals additional HLA class I and class II alleles associated with Type 1 diabetes and age at onset

Provisionally accepted
Antonietta Robino Antonietta Robino 1Elena Bevilacqua Elena Bevilacqua 2Luana Aldegheri Luana Aldegheri 1Andrea Conti Andrea Conti 1Valentina Bazzo Valentina Bazzo 2Gianluca Tornese Gianluca Tornese 1,3Eulalia Catamo Eulalia Catamo 1*
  • 1 Istituto Materno Infantile, IRCCS "Burlo Garofolo", Trieste, Italy
  • 2 Azienda Sanitaria Universitaria Giuliano Isontina, Trieste, Italy
  • 3 University of Trieste, Trieste, Friuli-Venezia Giulia, Italy

The final, formatted version of the article will be published soon.

    Introduction: Type 1 diabetes is an autoimmune disease with an significant genetic component, played mainly by the HLA class II genes. Although evidence on the role of HLA class I genes in developing type 1 diabetes and its onset have emerged, current HLA screening is limited to determining DR3 and DR4 haplotypes.This study aimed to investigate the role of HLA genes on type 1 diabetes risk and age of onset by extensive typing.Methods: This study included 115 children and young adults with type 1 diabetes for whom typing of HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1 and -DPB1 genes was conducted using Next Generation Sequencing.Results: We observed that 13% of type 1 diabetes subjects had non-classical HLA haplotypes that predispose to diabetes. We also found that compared to type 1 diabetes subjects with classical HLA haplotypes, non-classical HLA subjects had a significantly higher frequency of HLA-B*39:06:02 (p-value=0.01) and HLA-C*07:02:01 (p-value=0.03) alleles, known to be involved in activating the immune response. Non-classical HLA subjects also presented peculiar clinical features compared to classical HLA subjects, such as multiple diabetic antibodies and the absence of other autoimmune diseases (i.e., coeliac disease and thyroiditis).We also observed that subjects with early onset had a higher frequency of DQ2/DQ8 genotype than late-onset individuals. Moreover, subjects with late-onset had a higher frequency of alleles HLA-B*27 (p-value=0.003), HLA-C*01:02:01 (p-value=0.027) and C*02:02:02 (p-value=0.01), known to be associated with increased protection against viral infections.Discussion: This study reveals a broader involvement of the HLA locus in the development and onset of type 1 diabetes, providing insights into new possible disease prevention and management strategies.

    Keywords: age at onset, human leukocyte antigen, next generation sequencing, Paediatric, type 1 diabetes

    Received: 03 May 2024; Accepted: 22 Jul 2024.

    Copyright: © 2024 Robino, Bevilacqua, Aldegheri, Conti, Bazzo, Tornese and Catamo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Eulalia Catamo, Istituto Materno Infantile, IRCCS "Burlo Garofolo", Trieste, Italy

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