Circulating circular RNA profiles associated with celiac disease seropositivity in children with type 1 diabetes
IntroductionThe frequency of celiac disease autoantibody (CDAb) positivity in type 1 diabetes (T1D) has increased due to unclear mechanisms, including autoimmune injury. Circular ribonucleic acids (circRNAs) participate in autoimmune diseases, but the roles of circRNAs in T1D with CDAbs are currentl...
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| Format: | Article |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2022.960825/full |
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| author | Juan-juan Zhang Jun-qi Wang Xu Xu Li-dan Zhang Cai-ping Zhang Wen-li Lu Wei-qiong Gu Zhi-ya Dong Yuan Xiao Zhen-wei Xia |
| author_facet | Juan-juan Zhang Jun-qi Wang Xu Xu Li-dan Zhang Cai-ping Zhang Wen-li Lu Wei-qiong Gu Zhi-ya Dong Yuan Xiao Zhen-wei Xia |
| author_sort | Juan-juan Zhang |
| collection | DOAJ |
| description | IntroductionThe frequency of celiac disease autoantibody (CDAb) positivity in type 1 diabetes (T1D) has increased due to unclear mechanisms, including autoimmune injury. Circular ribonucleic acids (circRNAs) participate in autoimmune diseases, but the roles of circRNAs in T1D with CDAbs are currently unknown. This study aimed to determine the frequency of CDAbs in Chinese children with T1D and describe the relationship between CDAbs and circRNAs.Materials and methodsEighty patients diagnosed with T1D were screened for CDAbs and CD-predisposing genes, and circRNAs in peripheral blood mononuclear cells (PBMCs) were collected from 47 patients. The Gene Expression Omnibus (GEO) database was searched for candidate circRNAs in related studies on T1D PBMCs. Data on clinical characteristics (i.e., blood glucose control, residual islet function, and daily insulin dosage) and immunophenotypes (i.e., islet autoantibodies and immune cell subsets) were collected.ResultsIn total, 35.0% of patients were positive for CDAbs. CD-predisposing genes accounted for 52.5% of the genes, and no significant difference in frequency was found between the CDAb-positive (CDAb+) and CDAb-negative (CDAb–) groups. In addition, among the differentially expressed circRNAs from the GEO database, five highly conserved circRNAs homologous to humans and mice were screened, and only the expression of hsa_circ_0004564 in the CDAb+ group significantly decreased (CDAb+ vs. CDAb–:1.72 ± 1.92 vs. 11.12 ± 8.59, p = 6.0 × 10–6), while the expression of hsa_circ_0004564 was upregulated in the general T1D population. Moreover, its parental gene RAPH1 was significantly upregulated (CDAb+ vs. CDAb–:1.26 ± 0.99 vs. 0.61 ± 0.46, p = 0.011). Importantly, the positive correlation between hsa_circ_0004564 and CD3+ cells was validated in children with T1D after adjustments for CDAbs (p = 0.029), while there were no correlations between hsa_circ_0004564 and clinical characteristics or other immune cell subsets (i.e., CD4+ T cells, CD8+ T cells, and natural killer cells).ConclusionThis study highlights the importance of screening for CD in Chinese children with T1D, considering the high prevalence of CDAb positivity and CD-predisposing genes. The profile of candidate circRNAs in children with T1D with CDAbs was different from that in previous reports on general T1D patients from the GEO database. Moreover, hsa_circ_0004564 and its parental gene RAPH1 may be new targets for studying immune mechanisms in children with T1D and CD. |
| first_indexed | 2024-04-12T03:14:52Z |
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| id | doaj.art-f669d4923ab44e788ca2599c00e3902d |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-04-12T03:14:52Z |
| publishDate | 2022-09-01 |
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| series | Frontiers in Pediatrics |
| spelling | doaj.art-f669d4923ab44e788ca2599c00e3902d2022-12-22T03:50:14ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602022-09-011010.3389/fped.2022.960825960825Circulating circular RNA profiles associated with celiac disease seropositivity in children with type 1 diabetesJuan-juan Zhang0Jun-qi Wang1Xu Xu2Li-dan Zhang3Cai-ping Zhang4Wen-li Lu5Wei-qiong Gu6Zhi-ya Dong7Yuan Xiao8Zhen-wei Xia9Department of Pediatrics, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, ChinaDepartment of Pediatrics, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, ChinaDepartment of Pediatrics, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, ChinaDepartment of Pediatrics, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, ChinaDepartment of Pediatrics, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, ChinaDepartment of Pediatrics, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, ChinaDepartment of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, ChinaDepartment of Pediatrics, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, ChinaDepartment of Pediatrics, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, ChinaDepartment of Pediatrics, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, ChinaIntroductionThe frequency of celiac disease autoantibody (CDAb) positivity in type 1 diabetes (T1D) has increased due to unclear mechanisms, including autoimmune injury. Circular ribonucleic acids (circRNAs) participate in autoimmune diseases, but the roles of circRNAs in T1D with CDAbs are currently unknown. This study aimed to determine the frequency of CDAbs in Chinese children with T1D and describe the relationship between CDAbs and circRNAs.Materials and methodsEighty patients diagnosed with T1D were screened for CDAbs and CD-predisposing genes, and circRNAs in peripheral blood mononuclear cells (PBMCs) were collected from 47 patients. The Gene Expression Omnibus (GEO) database was searched for candidate circRNAs in related studies on T1D PBMCs. Data on clinical characteristics (i.e., blood glucose control, residual islet function, and daily insulin dosage) and immunophenotypes (i.e., islet autoantibodies and immune cell subsets) were collected.ResultsIn total, 35.0% of patients were positive for CDAbs. CD-predisposing genes accounted for 52.5% of the genes, and no significant difference in frequency was found between the CDAb-positive (CDAb+) and CDAb-negative (CDAb–) groups. In addition, among the differentially expressed circRNAs from the GEO database, five highly conserved circRNAs homologous to humans and mice were screened, and only the expression of hsa_circ_0004564 in the CDAb+ group significantly decreased (CDAb+ vs. CDAb–:1.72 ± 1.92 vs. 11.12 ± 8.59, p = 6.0 × 10–6), while the expression of hsa_circ_0004564 was upregulated in the general T1D population. Moreover, its parental gene RAPH1 was significantly upregulated (CDAb+ vs. CDAb–:1.26 ± 0.99 vs. 0.61 ± 0.46, p = 0.011). Importantly, the positive correlation between hsa_circ_0004564 and CD3+ cells was validated in children with T1D after adjustments for CDAbs (p = 0.029), while there were no correlations between hsa_circ_0004564 and clinical characteristics or other immune cell subsets (i.e., CD4+ T cells, CD8+ T cells, and natural killer cells).ConclusionThis study highlights the importance of screening for CD in Chinese children with T1D, considering the high prevalence of CDAb positivity and CD-predisposing genes. The profile of candidate circRNAs in children with T1D with CDAbs was different from that in previous reports on general T1D patients from the GEO database. Moreover, hsa_circ_0004564 and its parental gene RAPH1 may be new targets for studying immune mechanisms in children with T1D and CD.https://www.frontiersin.org/articles/10.3389/fped.2022.960825/fulltype 1 diabetesceliac disease autoantibodiesislet autoantibodiescellular immunityhuman leukocyte antigencircular RNAs |
| spellingShingle | Juan-juan Zhang Jun-qi Wang Xu Xu Li-dan Zhang Cai-ping Zhang Wen-li Lu Wei-qiong Gu Zhi-ya Dong Yuan Xiao Zhen-wei Xia Circulating circular RNA profiles associated with celiac disease seropositivity in children with type 1 diabetes Frontiers in Pediatrics type 1 diabetes celiac disease autoantibodies islet autoantibodies cellular immunity human leukocyte antigen circular RNAs |
| title | Circulating circular RNA profiles associated with celiac disease seropositivity in children with type 1 diabetes |
| title_full | Circulating circular RNA profiles associated with celiac disease seropositivity in children with type 1 diabetes |
| title_fullStr | Circulating circular RNA profiles associated with celiac disease seropositivity in children with type 1 diabetes |
| title_full_unstemmed | Circulating circular RNA profiles associated with celiac disease seropositivity in children with type 1 diabetes |
| title_short | Circulating circular RNA profiles associated with celiac disease seropositivity in children with type 1 diabetes |
| title_sort | circulating circular rna profiles associated with celiac disease seropositivity in children with type 1 diabetes |
| topic | type 1 diabetes celiac disease autoantibodies islet autoantibodies cellular immunity human leukocyte antigen circular RNAs |
| url | https://www.frontiersin.org/articles/10.3389/fped.2022.960825/full |
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