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

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Background: 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. Methods: 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 ∗ 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. Results: The most common haplotype found in participants with T1D was HLA‐(DR3)‐DQA1 ∗ 05‐DQB1 ∗ 02 haplotype (36.4%) (OR = 5.0; p < 0.000001). In addition, HLA‐DRB1 ∗ 0405‐DQA1 ∗ 03‐DQB1 ∗ 02 (19.3%, OR = 10.8; p < 0.000001), HLA‐DRB1 ∗ 0405‐DQA1 ∗ 03‐DQB1 ∗ 0302 (9.2%, OR = 3.1; p = 0.001), and HLA‐DRB1 ∗ 0401‐DQA1 ∗ 03‐DQB1 ∗ 0302 (3.2%, OR = 20.0; p = 0.002) were significantly increased among T1D patients. Conversely, HLA‐(DR15)‐DQB1 ∗ 0602, HLA‐(DR13)‐DQB1 ∗ 0603, HLA‐(DR1/10)‐DQB1 ∗ 0501, HLA‐(DR13)‐DQB1 ∗ 0604, HLA‐DRB1 ∗ 0404‐DQA1 ∗ 03‐DQB1 ∗ 04, HLA‐(DR7)‐DQA1 ∗ 0201‐DQB1 ∗ 02, HLA‐(DR11/12/13)‐DQA1 ∗ 05‐DQB1 ∗ 0301, and HLA‐DRB1 ∗ 0403‐DQA1 ∗ 03‐DQB1 ∗ 0302 were noted as the most protective haplotypes with a significant p 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 ( p < 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 ( p < 0.0001). Individuals carrying DR4‐DQ8 or DR3‐DQ2 haplotypes exhibited a higher prevalence of IA‐2A and tTGA ( p ≤ 0.05). Conclusions: 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.

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