摘要 目的:明确1型糖尿病(T1DM)儿童甲状腺抗体阳性的发生率及其相关因素。方法:回顾性分析我院2005年5月至2011年4月T1DM病例的临床资料,分析甲状腺球蛋白抗体(TGAb)、甲状腺过氧化物酶抗体(TPOAb)与细胞因子IL-2、IL-4、IL-6、IL-10、TNF、IFN-γ和CD3+、CD4+、CD8+淋巴细胞的关系。结果:经筛选后共获得甲状腺双抗体资料完整的T1DM患儿186例,其中甲状腺双抗体正常143例,甲状腺抗体阳性43例(23.1%),其中双抗体阳性21例。诊断为自身免疫性多腺体综合征3型变异型患儿18例(9.7%)。甲状腺抗体阳性组有糖尿病家族史的比例显著高于甲状腺抗体正常组(27.9% vs 14.7%,P<0.05)。甲状腺抗体阳性组患儿年龄大于甲状腺抗体正常组(10.1±3.2岁vs 8.1±4.0岁,P<0.05)。甲状腺抗体阳性组IL-2水平显著高于甲状腺抗体正常组(4.48 ±1.27 pg/mL vs 2.82 ±0.84 pg/mL,P<0.05),而其CD3+细胞比例低于甲状腺抗体正常组[(61±11)% vs (66±11)%, P<0.05)]。结论:儿童T1DM甲状腺抗体阳性率增高可能与遗传背景和T细胞免疫功能紊乱,尤其是IL-2异常升高有关。
Abstract:OBJECTIVE: To investigate the prevalence of positive thyroid antibodies in children with type 1 diabetes mellitus (T1DM) and its influencing factors. METHODS: The clinical data of T1DM children who were treated in the Children′s Hospital of Zhejiang University from May 2005 to April 2011 were retrospectively studied. The relationships of thyroid globulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) with cytokines IL-2, IL-4, IL-6, IL-10, TNF and IFN-γ were evaluated, and the percentages of CD3+, CD4+ and CD8+ T-lymphocytes in peripheral blood were examined. RESULTS: A total of 186 T1DM children with complete data of both TGAb and TPOAb were included in the study, among whom 143 with normal TGAb and TPOAb levels and 43 (23.1%) presented with positive thyroid antibody (including 21 cases with both positive TGAb and positive TPOAb). Eighteen cases (9.7%) were diagnosed as autoimmune polyglandular syndrome type 3 variant (APS3v). Significantly more patients in the positive thyroid antibody group had a family history of diabetes than in the negative thyroid antibody group (27.9% vs 14.7%; P<0.05). The average age of the positive thyroid antibody group was 10.1±3.2 years, which was significantly greater than that in the negative thyroid antibody group (8.1±4.0 years) (P<0.05). The IL-2 level (4.48 ±1.27 pg/mL vs 2.82 ±0.84 pg/mL, P<0.05) and the percentage of peripheral CD3+ T-lymphocyte [(61±11)% vs (66±11)%; P<0.05] were also different between the positive and negative thyroid antibody groups. CONCLUSIONS: Genetic background and abnormal function of T-lymphocytes (especially higher IL-2 level) may be involved in the elevated prevalence of positive thyroid antibody in T1DM children.
[5]Dittmar M, Kahaly GJ. Genetics of the autoimmune polyglandular syndrome type 3 variant[J]. Thyroid, 2010, 20(7): 737-743.
[6]Goodwin G, Volkening LK, Laffel LM. Younger age at onset of type 1 diabetes in concordant sibling pairs is associated with increased risk for autoimmune thyroid disease[J]. Diabetes Care, 2006, 29(6): 1397-1398.
[7]American Diabetes Association. Standards of medical care in diabetes--2007[J]. Diabetes Care, 2007, 30(Suppl 1):S4-S41.
[9]Villano MJ, Huber AK, Greenberg DA, Golden BK, Concepcion E, Tomer Y. Autoimmune thyroiditis and diabetes: dissecting the joint genetic susceptibility in a large cohort of multiplex families[J]. J Clin Endocrinol Metab, 2009, 94(4): 1458-1466.
[10]Kordonouri O, Klinghammer A, Lang EB, Grüters-Kieslich A, Grabert M, Holl RW. Thyroid autoimmunity in children and adolescents with type 1 diabetes: a multicenter survey[J]. Diabetes Care, 2002, 25(8):1346-1350.
[11]Hirschhorn JN. Genetic epidemiology of type 1 diabetes[J]. Pediatr Diabetes, 2003, 4(2): 87-100.
[12]Dong GP, Yu ZS, Liang L, Zou CC, Fu JF, Wang CL. IL-18 gene promoter -137C/G and -607C/A polymorphisms in Chinese Han children with type 1 diabetes mellitus[J]. Int J Immu nogenet, 2007, 34(2): 75-79.
[13]Huber A, Menconi F, Corathers S, Jacobson EM, Tomer Y. Joint genetic susceptibility to type 1 diabetes and autoimmune thyroiditis: from epidemiology to mechanisms[J]. Endocr Rev, 2008, 29(6): 697-725.