Background:Graves'ophthalmopathy(GO)occurs commonly in children with Graves'disease(GD).However,there are limited studies on the clinical manifestations and thyroid autoantibodies in pediatric GO.The aim of th...Background:Graves'ophthalmopathy(GO)occurs commonly in children with Graves'disease(GD).However,there are limited studies on the clinical manifestations and thyroid autoantibodies in pediatric GO.The aim of this study was to investigate the prevalence and risk factors of GO in childhood GD.Methods:Clinical and biochemical data from children and adolescents with GD were retrospectively reviewed.Eighty patients under 19 years of age were included in the present study.We compared the clinical and biochemical differences between patients with and without GO.Results:Thirty-nine percent of the patients had GO,and 81%of the GO patients were females.Of these,two patients showed unilateral GO.Triiodothyronine(T3)levels were higher in GO patients than in those without GO.Anti-thyroglobulin antibody and thyroid stimulating hormone receptor antibody titers were not significantly different between the two groups.Anti-thyroid peroxidase antibody(TPO Ab)positivity was 68%in the patients with GO and only 47%in the patients without GO.In multivariate regression analysis,high T3 levels and TPO Ab positivity were related to the presence of GO.Conclusion:In children and adolescents with GD,TPO Ab positivity and high T3 levels could act as predictive factors for the presence of GO.展开更多
Purpose:To investigate the role of N6-methyladenosine(m^(6)A)RNA modification in the pathogenesis of Graves'ophthalmopathy(GO).Methods:Surgically excised extraocular muscles from 7 patients with GO and 5 subjects ...Purpose:To investigate the role of N6-methyladenosine(m^(6)A)RNA modification in the pathogenesis of Graves'ophthalmopathy(GO).Methods:Surgically excised extraocular muscles from 7 patients with GO and 5 subjects without GO were used.The global m^(6)A levels in the specimens were determined using an m^(6)A RNA methylation quantification kit.RNA sequencing(RNA-seq)was used to analyze the molecules involved in the regulation of m^(6)A RNA methylation and the differential expression of mRNAs between the two groups(4 eyes,respectively).The expression of m^(6)A RNA modification genes was evaluated by real-time PCR.The functional implications of the gene alterations between the GO and control specimens were determined by Gene Ontology analysis.Results:The m^(6)A level was significantly increased in the specimens of GO patients compared to the control specimens(P<0.05).The expression of m^(6)A methylation regulators,such as WT1 associated protein(WTAP),alkylation repair homolog protein 5(ALKBH5),E74 like ETS transcription factor 3(ELF3),YTH N6-methyladenosine RNA binding protein 2(YTHDF2),YTHDF3 and YTH domain containing 2(YTHDC2),was significantly upregulated(P<0.05).Gene Ontology enrichment analysis showed that the most highly upregulated genes and biological pathways were related to the immune response and inflammatory processes such as lymphocyte activation,leukocyte differentiation,cytokine production and cytokine-mediated signaling pathways.Conclusions:Our results suggest that m^(6)A methylation may play a critical role in the pathogenesis of GO and that targeting genes that regulate m^(6)A methylation may provide a new therapeutic approach for GO.展开更多
文摘Background:Graves'ophthalmopathy(GO)occurs commonly in children with Graves'disease(GD).However,there are limited studies on the clinical manifestations and thyroid autoantibodies in pediatric GO.The aim of this study was to investigate the prevalence and risk factors of GO in childhood GD.Methods:Clinical and biochemical data from children and adolescents with GD were retrospectively reviewed.Eighty patients under 19 years of age were included in the present study.We compared the clinical and biochemical differences between patients with and without GO.Results:Thirty-nine percent of the patients had GO,and 81%of the GO patients were females.Of these,two patients showed unilateral GO.Triiodothyronine(T3)levels were higher in GO patients than in those without GO.Anti-thyroglobulin antibody and thyroid stimulating hormone receptor antibody titers were not significantly different between the two groups.Anti-thyroid peroxidase antibody(TPO Ab)positivity was 68%in the patients with GO and only 47%in the patients without GO.In multivariate regression analysis,high T3 levels and TPO Ab positivity were related to the presence of GO.Conclusion:In children and adolescents with GD,TPO Ab positivity and high T3 levels could act as predictive factors for the presence of GO.
基金This work was supported by grants from the National Natural Science Foundation of China(grant nos.81770943 and 81873681)the Beijing Municipal Science and Technology Commission(Capital Char-acteristic Clinic Applied Research Project,Z161100000516037).
文摘Purpose:To investigate the role of N6-methyladenosine(m^(6)A)RNA modification in the pathogenesis of Graves'ophthalmopathy(GO).Methods:Surgically excised extraocular muscles from 7 patients with GO and 5 subjects without GO were used.The global m^(6)A levels in the specimens were determined using an m^(6)A RNA methylation quantification kit.RNA sequencing(RNA-seq)was used to analyze the molecules involved in the regulation of m^(6)A RNA methylation and the differential expression of mRNAs between the two groups(4 eyes,respectively).The expression of m^(6)A RNA modification genes was evaluated by real-time PCR.The functional implications of the gene alterations between the GO and control specimens were determined by Gene Ontology analysis.Results:The m^(6)A level was significantly increased in the specimens of GO patients compared to the control specimens(P<0.05).The expression of m^(6)A methylation regulators,such as WT1 associated protein(WTAP),alkylation repair homolog protein 5(ALKBH5),E74 like ETS transcription factor 3(ELF3),YTH N6-methyladenosine RNA binding protein 2(YTHDF2),YTHDF3 and YTH domain containing 2(YTHDC2),was significantly upregulated(P<0.05).Gene Ontology enrichment analysis showed that the most highly upregulated genes and biological pathways were related to the immune response and inflammatory processes such as lymphocyte activation,leukocyte differentiation,cytokine production and cytokine-mediated signaling pathways.Conclusions:Our results suggest that m^(6)A methylation may play a critical role in the pathogenesis of GO and that targeting genes that regulate m^(6)A methylation may provide a new therapeutic approach for GO.
