NOD.β2m～(null).HHD Mouse Autoreactive T Cell Epitope Profile Study

Part ⅠExplore and analyze the epitope spectrum of NOD.β2mnu null.HHD miceObjective:To explore auto-reactive T cell epitope mapping of NOD.[32mnull.HHD mice in different durations,observe the variances of the number,response strength and spectrum.Methods:The NOD.β2mnull.HHD mice were divided into four groups,5-week,10-week,15-week,25-week group.Pathological changes of islets were observed under microscope after HE staining,insulitis scores were also been calculated.Taking advantage of a panel of 28 HLA-A*0201-restricted CD8+T cell epitopes derived from 7 antigens,we implemented an enzyme-linked immunospot assay to detect the response of interferon-y secreting CD8+T cells against antigen-specific 28 epitopes in NOD.p2mnull.HHD mice.Results:The average insulitis score of that of 5-week,10-week,15-week,25-week group was 0.52±0.76、1.05±1.02、1.45±1.37、1.94±1.32(P<0.001=.The number of epitopes which had tested positive response were 12、17、24、17 respectively.Each mice in different groups showed positive response to 2.8,4.0,9.0 and 3.3 epitopes on average.The constitutions of response intensity of all groups were almost the same.The epitope spectrum showed the tendency of "epitope spreading".INS-5 and ZnT8-1 were the positive epitopes of 5-week group,INS-5、IGRP-2、ZnT8-1、ZnT8-2 of 10-week group,INS-3、GAD-2、IGRP-1、IGRP-2、IGRP-3、IGRP-4、IA2-3、ZnT8-1 of 15-week group。The relative positive epitopes of 25-week group were GAD-2 and ZnT8-5.The epitopes located outside of the insulin secretory granules had a increased proportions of whole positive responses as the disease progressing.Conclusion:The mice showed progressive insulitis as the disease developing.Variations existed in the specificity of the CD8+T-cell response between individual mice,while there were some epitopes of which the positive rate were higher than or near 50%,which provided the basis for the individualized T cell epitope vaccine therapy.Part ⅡCross-cultural adaption and psychometric properties of the Chinese version of the Diabetes Behavior Rating ScaleObjective:Self-care behavior plays a major role in diabetic management,however,in the Mainland of China,mature scale has not been developed to evaluate the compliance of self-care,especially for the youths.The purpose of this study is to cross-culturally adapt the Chinese version of the Diabetes Behavior Rating Scale(DBRS),and primarily evaluate its psychometric properties among the type 1 diabetes patients with insulin injection therapy.Methods:The instrument translation included translation,back translation and culture adaption.Psychometric properties of the Chinese version of the DBRS were assessed in a sample of 116 youths(aged 8-26 yr)with type 1 diabetes adapting insulin injection therapy.Statistical analysis included construct validity(exploring factor analysis),internal consistency,test-retest reliability,subscale inter-correlations and criterion validity.The relationship between the glycemic control and diabetic self-care was also explored.Results:Through the exploring factor analysis,the Chinese version of the DBRS was classified to four subscales(temporary response,glucose monitoring,insulin administration and daily life).Cronbach’s a for the total scale was 0.92.The mean inter-item and item-total correlations were 0.35 and 0.54 respectively.Test-retest reliability shows good temporal stability(r=0.81,p=0.001).Negative correlations were found between DBRS scores with the Diabetes Distress Scale(DDS)scores(r=-0.32,p=0.003)and HbAlc levels(r=-0.36,p=0.002).Higher levels of diabetic self-care were significantly associated with lower HbA1c levels.Conclusion:The Chinese version of the DBRS for type 1 diabetes patients with insulin injection therapy is well translated and culturally adapted.The Chinese version shows good overall reliability and validity and appears to be a valuable tool for assessing the diabetic self-care behaviors.Higher DBRS scores correlate with better glycemic control.