Adugna Negussie Gudeta, Alexander Lind, Alemayehu Girma, Johanna Lempainen, Jorma Ilonen, Daniel Agardh
{"title":"HLA基因分型埃塞俄比亚1型糖尿病儿童和青少年中糖尿病、乳糜泻和甲状腺相关自身抗体:一项横断面研究","authors":"Adugna Negussie Gudeta, Alexander Lind, Alemayehu Girma, Johanna Lempainen, Jorma Ilonen, Daniel Agardh","doi":"10.1155/pedi/8258430","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background:</b> 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. <b>Methods:</b> 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<i></i> <sup><i>∗</i></sup> 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. <b>Results:</b> The most common haplotype found in participants with T1D was HLA-(DR3)-DQA1<i></i> <sup><i>∗</i></sup> 05-DQB1<i></i> <sup><i>∗</i></sup> 02 haplotype (36.4%) (OR = 5.0; <i>p</i> < 0.000001). In addition, HLA-DRB1<i></i> <sup><i>∗</i></sup> 0405-DQA1<i></i> <sup><i>∗</i></sup> 03-DQB1<i></i> <sup><i>∗</i></sup> 02 (19.3%, OR = 10.8; <i>p</i> < 0.000001), HLA-DRB1<i></i> <sup><i>∗</i></sup> 0405-DQA1<i></i> <sup><i>∗</i></sup> 03-DQB1<i></i> <sup><i>∗</i></sup> 0302 (9.2%, OR = 3.1; <i>p</i>=0.001), and HLA-DRB1<i></i> <sup><i>∗</i></sup> 0401-DQA1<i></i> <sup><i>∗</i></sup> 03-DQB1<i></i> <sup><i>∗</i></sup> 0302 (3.2%, OR = 20.0; <i>p</i>=0.002) were significantly increased among T1D patients. Conversely, HLA-(DR15)-DQB1<i></i> <sup><i>∗</i></sup> 0602, HLA-(DR13)-DQB1<i></i> <sup><i>∗</i></sup> 0603, HLA-(DR1/10)-DQB1<i></i> <sup><i>∗</i></sup> 0501, HLA-(DR13)-DQB1<i></i> <sup><i>∗</i></sup> 0604, HLA-DRB1<i></i> <sup><i>∗</i></sup> 0404-DQA1<i></i> <sup><i>∗</i></sup> 03-DQB1<i></i> <sup><i>∗</i></sup> 04, HLA-(DR7)-DQA1<i></i> <sup><i>∗</i></sup> 0201-DQB1<i></i> <sup><i>∗</i></sup> 02, HLA-(DR11/12/13)-DQA1<i></i> <sup><i>∗</i></sup> 05-DQB1<i></i> <sup><i>∗</i></sup> 0301, and HLA-DRB1<i></i> <sup><i>∗</i></sup> 0403-DQA1<i></i> <sup><i>∗</i></sup> 03-DQB1<i></i> <sup><i>∗</i></sup> 0302 were noted as the most protective haplotypes with a significant <i>p</i> 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 (<i>p</i> < 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 (<i>p</i> < 0.0001). Individuals carrying DR4-DQ8 or DR3-DQ2 haplotypes exhibited a higher prevalence of IA-2A and tTGA (<i>p</i> ≤ 0.05). <b>Conclusions:</b> 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>","PeriodicalId":19797,"journal":{"name":"Pediatric Diabetes","volume":"2025 ","pages":"8258430"},"PeriodicalIF":5.6000,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375835/pdf/","citationCount":"0","resultStr":"{\"title\":\"Diabetes, Celiac, and Thyroid-Related Autoantibodies in HLA Genotyped Ethiopian Children and Adolescents With Type 1 Diabetes: A Cross-Sectional Study.\",\"authors\":\"Adugna Negussie Gudeta, Alexander Lind, Alemayehu Girma, Johanna Lempainen, Jorma Ilonen, Daniel Agardh\",\"doi\":\"10.1155/pedi/8258430\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background:</b> 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. <b>Methods:</b> 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<i></i> <sup><i>∗</i></sup> 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. <b>Results:</b> The most common haplotype found in participants with T1D was HLA-(DR3)-DQA1<i></i> <sup><i>∗</i></sup> 05-DQB1<i></i> <sup><i>∗</i></sup> 02 haplotype (36.4%) (OR = 5.0; <i>p</i> < 0.000001). In addition, HLA-DRB1<i></i> <sup><i>∗</i></sup> 0405-DQA1<i></i> <sup><i>∗</i></sup> 03-DQB1<i></i> <sup><i>∗</i></sup> 02 (19.3%, OR = 10.8; <i>p</i> < 0.000001), HLA-DRB1<i></i> <sup><i>∗</i></sup> 0405-DQA1<i></i> <sup><i>∗</i></sup> 03-DQB1<i></i> <sup><i>∗</i></sup> 0302 (9.2%, OR = 3.1; <i>p</i>=0.001), and HLA-DRB1<i></i> <sup><i>∗</i></sup> 0401-DQA1<i></i> <sup><i>∗</i></sup> 03-DQB1<i></i> <sup><i>∗</i></sup> 0302 (3.2%, OR = 20.0; <i>p</i>=0.002) were significantly increased among T1D patients. Conversely, HLA-(DR15)-DQB1<i></i> <sup><i>∗</i></sup> 0602, HLA-(DR13)-DQB1<i></i> <sup><i>∗</i></sup> 0603, HLA-(DR1/10)-DQB1<i></i> <sup><i>∗</i></sup> 0501, HLA-(DR13)-DQB1<i></i> <sup><i>∗</i></sup> 0604, HLA-DRB1<i></i> <sup><i>∗</i></sup> 0404-DQA1<i></i> <sup><i>∗</i></sup> 03-DQB1<i></i> <sup><i>∗</i></sup> 04, HLA-(DR7)-DQA1<i></i> <sup><i>∗</i></sup> 0201-DQB1<i></i> <sup><i>∗</i></sup> 02, HLA-(DR11/12/13)-DQA1<i></i> <sup><i>∗</i></sup> 05-DQB1<i></i> <sup><i>∗</i></sup> 0301, and HLA-DRB1<i></i> <sup><i>∗</i></sup> 0403-DQA1<i></i> <sup><i>∗</i></sup> 03-DQB1<i></i> <sup><i>∗</i></sup> 0302 were noted as the most protective haplotypes with a significant <i>p</i> 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 (<i>p</i> < 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 (<i>p</i> < 0.0001). Individuals carrying DR4-DQ8 or DR3-DQ2 haplotypes exhibited a higher prevalence of IA-2A and tTGA (<i>p</i> ≤ 0.05). <b>Conclusions:</b> 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>\",\"PeriodicalId\":19797,\"journal\":{\"name\":\"Pediatric Diabetes\",\"volume\":\"2025 \",\"pages\":\"8258430\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2025-08-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375835/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pediatric Diabetes\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1155/pedi/8258430\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Diabetes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/pedi/8258430","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Diabetes, Celiac, and Thyroid-Related Autoantibodies in HLA Genotyped Ethiopian Children and Adolescents With Type 1 Diabetes: A Cross-Sectional Study.
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.
期刊介绍:
Pediatric Diabetes is a bi-monthly journal devoted to disseminating new knowledge relating to the epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes in childhood and adolescence. The aim of the journal is to become the leading vehicle for international dissemination of research and practice relating to diabetes in youth. Papers are considered for publication based on the rigor of scientific approach, novelty, and importance for understanding mechanisms involved in the epidemiology and etiology of this disease, especially its molecular, biochemical and physiological aspects. Work relating to the clinical presentation, course, management and outcome of diabetes, including its physical and emotional sequelae, is considered. In vitro studies using animal or human tissues, whole animal and clinical studies in humans are also considered. The journal reviews full-length papers, preliminary communications with important new information, clinical reports, and reviews of major topics. Invited editorials, commentaries, and perspectives are a regular feature. The editors, based in the USA, Europe, and Australasia, maintain regular communications to assure rapid turnaround time of submitted manuscripts.