| Background:Graves disease (GD), also known as diffuse toxic goiter, is an autoimmunethyroid disease that associated with increased secretion of thyroid hormone. It hastypical symptoms of goiter and high metabolic syndrome, and it is also accompaniedby pathological change of limited fibrous tissue such as Graves ophthalmopathy(GO). So far we have recognized that GO is anorgan-specific autoimmune diseaseagainst extra-ocular muscle and the organizing tissues behind the eye ball, andcurrently this pathological change of fibrous tissue has more likely been consideredto reflect the potential autoimmune process. In GD the thyrotropin receptorantibodies (TRAb) is an important immune indicator and it can also be detected inserum of the most GO patients. However the clinical sensitivity and specificity of themethods of TRAb detection is not very high so that it can not well indicate theprogress and remission of GD and predict the merge of GO. Therefore it is needed todetect TRAb with other autoimmune antibodies which can indicate the existence ofimmune dysfunction to improve prediction and diagnosis value of GD and GO.Zinc transporter8(ZnT8) is a recently discovered auto-antigen of islet βcelland it is reported that this protein can also be expressed in adipose tissue, peripheralblood lymphocytes, thyroid epithelial cells and adrenal. Zinc transporter8autoantibodies (ZnT8A) is associated with islet autoimmune disease and it ispossible to become an autoimmune marker of other autoimmune disease. Thereforethe study focused on the existence of autoantibodies of TRAb and ZnT8A in thesera of GD and GO patients and found the correlation between these twoautoantibodies to provide possible combination in detecting these autoimmuneantibodies in the study on GD and GO pathogenesis and diagnosis. Objective:To detect distributions of the thyrotropin receptor antibodies (TRAb), zinctransporter8antibodies (ZnT8A) and glutamate decarboxylase antibodies (GADA)in health people and patients with Graves disease. To compare the serumautoantibodies levels of these antibodies and analyze correlation between theseantibodies in patients with Graves disease and Graves ophthalmopathy.Method:Randomly selecting52cases with Graves disease who admitted hospitalizationand outpatient treatment in our hospital from November2009to June2011. Bycollect clinical information including general information and thyroid function andother clinical data, they were divided into two groups according to whether therewere occurred ophthalmopathy:(1) pure GD group: A total of30cases, of which5cases were male and25females, age (22~61) years, with an average(43.30±13.67)years, duration (41.01±62.35) months.(2) GO accompanied GDgroup: A total of22cases, of which8cases were male and14were female, age(17~68) years, with an average age (42.64±12.69) years, duration (30.25±47.60)months.70healthy volunteers who were without heart, brain, liver, kidney, andother chronic diseases were recruited, and they had no family history of thyroiddisease and other autoimmune disease history. They were as healthy control group,of which29cases were male and41were female, age (13~50) years, with anaverage age (26.27±14,21) years. These subjects were informed the studies andsigned the written consent. From these subjects the fasting wenous blood wasextracted and sera were prepared and stored in-20C until autoantibodies ofthyrotropin receptor, zinc transporter8and glutamate decarboxylase were measured.All experimental data were analyzed statistically.Results：（1）The clinical informations of the pure GD group and the pure GD group suchas age structure (t=0.466, P=0.498, P>0.05), duration (t=0.624, P=0.535, P>0.05) had no significant differences.（2）The positive percentage of thyrotropin receptor antibodies, zinc transporter8antibodies and glutamate decarboxylase antibodies in Graves disease patients were90.38%(47/52),19.23%(10/52) and76%(3/52). While in healthy control group thepositive percentage of these antibodies were0%(0/70),1.43%(1/70) and1.43%(1/70), respectively.（3）The TRAb lever of pure GD group was91.71±70.50U/L and GOaccompanying GD group was115.37±95.17U/L which no significant differencestatistically (t=0.391, P=0.534, P>0.05). The TRAb positive rates of two groupswere90.91%and90.0%, and there were no significant difference (Fisher’s ExactTest, P=0.10, P>0.05).（4）The ZnT8A levels of pure GD group and GO accompanying GD group were0.013±0.262and0.031±0.079respectively, the difference was statistically significant(t=7.645，P=0.008，P<0.01). The ZnT8positive rate of pure GD group was13.33%and GO accompanying GD group was27.27%which no significant differencestatistically (Fisher’s Exact Test, P=0.290, P>0.05).（5）There were no significant difference between GADA levels (t=1.269，P=0.265，P>0.05) and positive rates (Fisher’s Exact Test, P=0.567, P>0.05) of pureGD group and GO accompanying GD group.（6）There was no statistically linear correlation between TRAb and GADA in GDpatients. While there was linear correlation between TRAb and ZnT8A in GD patient(r=0.295，P<0.05), and the correlation was even stronger in TRAb positive GDpatients (r=0.521，P<0.01). It also showed a strong positive linear correlation inTRAb positive GO patients (r=0.677，P＜0.01).Conclusions：（1）ZnT8A plays an important role in the occurrence of GD, no matter of GOassociated or not.（2）ZnT8A levels were statistically higher in GO merger GD group than pure GDgroup, while TRAb and GADA levels had no significant difference statistically. Itindicates that ZnT8A can be seen as an autoimmune marker which can indicatethe existence of immune dysfunction and it also suggests that ZnT8A positive canindicate the higher risk of suffering from GO and can supply immunological index forearlier precaution, diagnosis and treatment of GO.（3）The ZnT8A positive rates of GO merger GD group were higher than pure GD group. Though there was no significant difference statistically, it still suggests that therole of ZnT8A may be different in the pathogenesis of GD and GO. Since the size ofsample of this study is small, this conclusion should be proved in a larger sample size.（4）There was no statistically linear correlation between TRAb and GADA in GDpatients. While there existed linear correlation between TRAb and ZnT8A in GDpatient (r=0.295), and the correlation was even stronger in TRAb positive GDpatients (r=0.521). There also showed a strong positive linear correlation in TRAbpositive GO patients (r=0.677). It suggests that ZnT8A is related with TRAb whichis specific antibody of Graves disease, and it has greater correlation between thesetwo antibodies in TRAb positive GO patients. ZnT8and TRAb testing may helpdiagnosis of GD and GO.（5）Since it is a retrospective study and the size of the sample is small, also whenwe were collecting cases we excluded type1diabetes and other autoimmune diseasesin patients with Graves disease, so it needs a larger sample size and follow up data toprospect whether or not these ZnT8positive GD patients will merge type1diabetesand other autoimmune disease. |
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