| Part ? Clinical Application of CD8~+ T cell Responses in Pediatrics and Adolescents with Type 1 Diabetes Objective: Type 1 diabetes is characterized by progressing ? cell destruction induced by CD8~+ T cell.The assay of CD8~+ lymphocytes is important for closely reflecting the dynamic revolution of islet autoimmunity.The aim of this study was to study the feature of CD8~+ T cell responses in pediatrics and adolescents with type 1 diabetes,optimize the testing protocol and evaluate the value of them on clinical application.Methods: Taken advantage of a panel of 28 HLA-A2–restricted CD8~+T-cell epitopes,we had implemented an enzyme-linked immunospot(ELISPOT)assay to detect the responses of interferon-? secreting CD8~+ T cell against islet-specific epitopes in 30 type 1 diabetic patients and 18 health controls.Results: The peptides GAD-2,Zn T8-4,Zn T8-1,Zn T8-3,PPI-3 had better diagnostic efficacy in pediatrics and adolescents with new-onset type 1 diabetes(all P < 0.007).The basic testing scheme in combination of 23 peptides reached high accuracy with sensitivity of 88.9% and specificity of 100%.Reduced epitopes to optimize protocols can achieve as high accuracy as the basic one,however the efficacy increased significantly(Positive peptides rate: 38.3%-45.4% v.s.26.8%,all P < 0.005).The positivity of CD8~+ T cell responses especially on peptides Zn T8-1,Zn T8-4 decreased significantly in long-standing patients(94.4% v.s.50%,P=0.035;Zn T8-1: 66.7% v.s.0%,P=0.014;Zn T8-4: 72.2% v.s.0%,P=0.003).Conclusion: Optimized testing schemes performed as well as basic one on identifying type 1 diabetes(Sensitivity: 88.9-100%,Specificity: 72.2-100%).Application of suitable scheme individually can improve the efficacy of diagnosis and application.Part ? Screening for Thyroid Autoimmunity in Type 1 Diabetes Objective: The aim of this study was to investigate in patients with type 1 diabetes(T1D): the prevalence of thyroid autoantibodies(T-Ab);the association between thyroid autoimmunity with either islet autoantibodies or thyroid function;and the differences of thyroid autoimmunity between adults and pediatrics.Methods: 491 T1 D patients were analyzed for thyroid autoimmunity in addition to islet autoantibodies and thyroid function.Results: 22% T1 D patients had thyroid autoantibodies(62% were female;P=0.000).Patients with T-Ab had higher prevalence of islet autoantibodies(all with P<0.05).While thyroid peroxidase(TPOAb)was positively associated with all the 5 islet autoantibodies(all with P< 0.05),thyroglobulin(TGAb)was only associated with glutamic acid decarboxylase(GADA,P=0.005).In addition,the positive number of islet autoantibodies was positively associated with the prevalence of T-Ab(30.2%,P=0.000).22.6% adults with T1 D had T-Ab,the number of adults with double anti-thyroid autoantibodies positivity was more than that in the pediatric group(prevalence of double T-Abs: 57.8% vs.36.4%,P=0.028).The presence of T-Ab was positively associated with serum thyroid-stimulating hormone(TSH)levels(P=0.008).The presence of both anti-thyroid antibodies was positively associated with thyroid dysfunction(prevalence of thyroid dysfunction: 64.2%vs.30.9%,P=0.002).Conclusion: Thyroid autoimmunity was commonly happened in adults and pediatrics with T1 D.Thyroid autoimmunity was associated with female gender,the persistence of GADA and multiple islet autoantibodies positivity.The risk of thyroid autoimmunity did not differ from adults to pediatrics;however,the thyroid autoimmunity was severe in the adults.Multiple anti-thyroid autoantibodies indicated thyroid dysfunction. |
PDF Full Text Request