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

IF 5.6 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Pediatric Diabetes Pub Date : 2025-08-17 eCollection Date: 2025-01-01 DOI:10.1155/pedi/8258430
Adugna Negussie Gudeta, Alexander Lind, Alemayehu Girma, Johanna Lempainen, Jorma Ilonen, Daniel Agardh
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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. 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引用次数: 0

摘要

背景:朗格汉斯胰岛中抗β细胞成分的自身抗体是1型糖尿病(T1D)的特征。埃塞俄比亚人1型糖尿病(T1D)的遗传和自身免疫决定因素尚未完全确定,研究表明,与高加索人相比,埃塞俄比亚人与T1D相关的自身抗体发生率较低。该研究旨在确定埃塞俄比亚患有T1D的儿童和青少年中与1型糖尿病(T1D)、乳糜泻(CD)和自身免疫性甲状腺疾病(AITD)相关的自身抗体以及人类白细胞抗原(HLA)基因型的发生情况。方法:这项横断面研究包括206名T1D儿童和青少年(年龄从1岁到18岁),中位病程为6年,以及200名年龄匹配的对照儿童(年龄从1岁到6岁)。参与者从埃塞俄比亚的Adama、Asella和Bishoftu医院招募。该研究涉及HLA等位基因的基因分型,特别是HLA- dqa1, DQB1和DRB1²* 04(包括DR4亚型)。此外,采用凝集PCR (ADAP)检测针对谷氨酸脱羧酶(GADA)、胰岛素瘤相关蛋白(IA-2A)、锌转运蛋白8 (ZnT8A)、组织转谷氨酰胺酶(tTGA)和甲状腺过氧化物酶(TPOA)的自身抗体。结果:T1D患者中最常见的单倍型为HLA-(DR3)- dqa1 ∗05-DQB1 ∗02 (36.4%)(OR = 5.0; p < 0.000001)。此外,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), HLA-DRB1 ∗0401-DQA1 ∗03-DQB1 ∗0302 (3.2%,OR = 20.0; p=0.002)在T1D患者中显著增加。相反,HLA-(DR15)- dqb1 ∗0602、HLA-(DR13)- dqb1 ∗0603、HLA-(DR1/10)- dqb1 ∗0604、HLA-(DR13)- dqb1 ∗0404-DQA1 ∗03-DQB1 ∗04、HLA-(DR7)- dqa1 ∗0201-DQB1 ∗0301、HLA-(DR11/12/13)- dqa1∗0403-DQA1 ∗0301和HLA- drb1 ∗0403-DQA1∗03-DQB1 ∗0302被认为是最具保护性的单倍型,p值显著,ORs范围为0.05 ~ 0.5。儿童和青少年T1D患者出现胰岛自身抗体的总频率为81.1%,而对照组为5.5% (p < 0.0001)。在比较T1D患者和对照组的抗体阳性率时,GADA为69%,IA-2A为24%,1.5%,ZnT8A为32%,2%,tTGA为14%,2%,TPOA为17%,5% (p < 0.0001)。携带DR4-DQ8或DR3-DQ2单倍型的个体IA-2A和tTGA患病率较高(p≤0.05)。结论:在埃塞俄比亚T1D患者中观察到撒哈拉以南非洲人群的典型HLA风险特征。此外,他们与T1D、CD和AITD相关的自身抗体的患病率明显较高,这与该地区早期的报告不同,但与在高加索人中观察到的模式一致。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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

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.

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来源期刊
Pediatric Diabetes
Pediatric Diabetes 医学-内分泌学与代谢
CiteScore
6.60
自引率
14.70%
发文量
141
审稿时长
4-8 weeks
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.
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