Diabetes, Celiac, and Thyroid‐Related Autoantibodies in HLA Genotyped Ethiopian Children and Adolescents With Type 1 Diabetes: A Cross‐Sectional Study

Abstract

<p><strong>Background:</strong> <br></p><p>Autoantibodies against β-cell components in the pancreatic islets of Langerhans are characteristic of type 1 diabetes (T1D). The genetic and autoimmune determinants of type 1 diabetes (T1D) in Ethiopians are not yet thoroughly characterized, with studies indicating a lower occurrence of autoantibodies related to T1D compared to Caucasians. The study aimed to determine the occurrence of autoantibodies related to type 1 diabetes (T1D), celiac disease (CD), and autoimmune thyroid disease (AITD) in conjunction with Human Leukocyte Antigen (HLA) genotype in Ethiopian children and adolescents with T1D.</p><p><strong>Methods:</strong> <br></p><p>This cross-sectional study included 206 children and adolescents with T1D (ranging from 1 to 18 years old) with a median disease duration of 6 years, alongside 200 age-matched control children (ranging from 1 to 6 years old). Participants were recruited from Adama, Asella, and Bishoftu Hospitals in Ethiopia. The study involved genotyping of HLA alleles, specifically HLA-DQA1, DQB1, and DRB1<em> </em>^∗04 (including DR4 subtypes). Additionally, autoantibodies targeting glutamic acid decarboxylase (GADA), insulinoma-associated protein (IA-2A), zinc transporter 8 (ZnT8A), tissue transglutaminase (tTGA), and thyroid peroxidase (TPOA) were analyzed using antibody detection by agglutination PCR (ADAP) assays.</p><p><strong>Results:</strong> <br></p><p>The most common haplotype found in participants with T1D was HLA-(DR3)-DQA1<em> </em>^∗05-DQB1<em> </em>^∗02 haplotype (36.4%) (OR = 5.0; <em>p</em> < 0.000001). In addition, HLA-DRB1<em> </em>^∗0405-DQA1<em> </em>^∗03-DQB1<em> </em>^∗02 (19.3%, OR = 10.8; <em>p</em> < 0.000001), HLA-DRB1<em> </em>^∗0405-DQA1<em> </em>^∗03-DQB1<em> </em>^∗0302 (9.2%, OR = 3.1; <em>p</em> = 0.001), and HLA-DRB1<em> </em>^∗0401-DQA1<em> </em>^∗03-DQB1<em> </em>^∗0302 (3.2%, OR = 20.0; <em>p</em> = 0.002) were significantly increased among T1D patients. Conversely, HLA-(DR15)-DQB1<em> </em>^∗0602, HLA-(DR13)-DQB1<em> </em>^∗0603, HLA-(DR1/10)-DQB1<em> </em>^∗0501, HLA-(DR13)-DQB1<em> </em>^∗0604, HLA-DRB1<em> </em>^∗0404-DQA1<em> </em>^∗03-DQB1<em> </em>^∗04, HLA-(DR7)-DQA1<em> </em>^∗0201-DQB1<em> </em>^∗02, HLA-(DR11/12/13)-DQA1<em> </em>^∗05-DQB1<em> </em>^∗0301, and HLA-DRB1<em> </em>^∗0403-DQA1<em> </em>^∗03-DQB1<em> </em>^∗0302 were noted as the most protective haplotypes with a significant <em>p</em> value and, with ORs ranging from 0.05 to 0.5. The overall frequency of any islet autoantibodies in children and adolescents with T1D was 81.1% compared to 5.5% in the control group (<em>p</em> < 0.0001). While comparing antibody positivity between individuals with T1D and controls, GADA was found in 69% versus 2%, IA-2A in 24% versus 1.5%, ZnT8A in 32% versus 2%, tTGA in 14% versus 2%, and TPOA in 17% versus 5%, respectively (<em>p</em> < 0.0001). Individuals carrying DR4-DQ8 or DR3-DQ2 haplotypes exhibited a higher prevalence of IA-2A and tTGA (<em>p</em> ≤ 0.05).</p><p><strong>Conclusions:</strong> <br></p><p>The HLA risk profile typical of sub-Saharan African population was observed in Ethiopians with T1D. Furthermore, they have a notably high prevalence of autoantibodies associated with T1D, CD, and AITD, which differs from earlier reports from the region but aligns with patterns observed in Caucasians.</p>