| Background:Thyroid associated ophthalmology(TAO),also known as Graves ophthalmopathy or infiltrative exophthalmos,is a common orbital disease.Also,it is autoimmune disease closely related to Graves disease,about 25% to 50% of patients with hyperthyroidism will be affected by TAO as well.The incidence of TAO in men is higher than in women,unlike Graves disease(GD).TAO can have a variety of clinical symptoms.The less severe cases can be classified as tears,photophobia.Slightly severe patients can be manifested as limited eye activity,diplopia,or prominent eye.About 3%-5% of the patients with serious condition have more serious eye disease or loss of vision.There is no significant order of occurrence between TAO patients' ocular manifestations and hyperthyroidism.For some TAO patients,their thyroid functions are worked as normal.Nevertheless,they might be under subclinical hyperthyroidism or only thyroid autoantibodies situation.The pathogenesis of TAO is inconclusive and patients with abnormal thyroid function and eye performance are not completely related to each other.Thyroid hormone is an important factor to maintain normal blood lipid metabolism and protein synthesis.When thyroid hormone is abnormal,it will affect the patient's blood glucose,blood lipid metabolism in varying degrees.The Apolipoprotein(apo)C4 gene is a member of the apolipoprotein C gene family.It is expressed in the liver and has predicted protein structural features of other genes.As a secreted protein,previous results shows that apolipoprotein C4 not only exist in the serum but also can be found in the body fluid,such as the patients' tears.More importantly,APOC4 is higher in tears of TAO patients.Human serum albumin is a major carrier of fatty acids.It affects the pharmacokinetics of many drugs and provides metabolizes for some ligands to make potential toxins harmless.It also plays an important role for both antioxidant capacity in plasma and the nature of the enzymes.At the same time,it has been proved that serum albumin has antioxidant property.As a plasma-derived tear protein,although itssize is tiny,its alteration could be closely related to systemic and eye diseases.Several studies on the imaging of TAO patients have confirmed that lacrimal gland is involved in the occurrence and development of TAO.Nevertheless,there is not enough research related to TAO patients' tears both in China and foreign Countries.The expression difference between of APOC4 and serum albumin in patients and healthy people is not known yet.Objective:Detection of APOC4 and serum albumin levels in serum and tears for healthy people and TAO patients to verify the trend of APOC4 and serum albumin in serum and tears of TAO patients can help to further explore the occurrence and development of lacrimal gland acinar cells in TAO.Finding the trends for TAO patients' biomarkers through monitoring and predicting may also help to develop new therapies.Materials and methods:A total of 28 patients with autoimmune thyroid disease were randomly selected in the Department of Endocrinology and Wards from September 2015 to December2017.General information and other clinical data for patients are recorded such as smoking history and family history of thyroid disease.At the same time,according to Graves disease classification criteria and clinical activity index(Clinical activity score,CAS)standard records,patients' eye-related conditions are collected as well.In addition,14 healthy controls were recruited,including 6 males and 8 females,with a mean age of45 ± 14 years.There were no significant differences in gender and age between the two groups.Also,there were no history of thyroid disease and no other autoimmunity history.All blood and tear samples were collected after their consent.By using centrifugation for the blood samples,serums were obtained and stored-80 ?.200 ul tears were been collected with a blunt tip of a 1 ml syringe and stored at-80?.Serum albumin and APOC4 were tested by using radioimmunoassay.the results were statistically analyzed.Results:1.Serum APOC4 expression in hyperthyroidism exophthalmus group and the expression of hyperthyroidism exophthalmus group were higher than that of healthy controls,and two more had statistically difference(z values 4.2731,4.2731,4.5029,p values < 0.001);Tears APOC4 expression in hyperthyroidism of exophthalmia group and the expression of hyperthyroidism exophthalmus group were higher than that ofhealthy controls,including hyperthyroidism exophthalmus group and hyperthyroidism non exophthalmos,hyperthyroidism exophthalmus compared group compared to healthy controls were statistically difference(z values 4.5041,5047,p values < 0.001),but in hyperthyroidism exophthalmus group and healthy controls and there is no difference between way(z = 0.3682,p = 0.928).2.To express human blood serum albumin in hyperthyroidism exophthalmus group and the expression of hyperthyroidism exophthalmus group were lower than that of healthy controls,and two more were statistically difference(z values 4.2731,4.2731,4.5029,p values 0.024,p < 0.001,p < 0.001).Tears in blood propagated expression in hyperthyroidism exophthalmus group and the expression of hyperthyroidism exophthalmus group were lower than that of healthy controls,and two more were statistically difference(z values 4.5041,,4.5047,0.3682,p values < 0.001).3.APOC4 in the serum in patients with GD group(including hyperthyroidism exophthalmos of exophthalmos and hyperthyroidism group)and healthy controls are statistically difference is compared between(z =-5.23,p < 0.001),the APOC4 tears in patients with TAO group(including hyperthyroidism exophthalmos of exophthalmos and hyperthyroidism group)and healthy controls are statistically difference is compared between(z =-2.83,p < 0.001).Blood propagated in the serum in patients with TAO group(including hyperthyroidism exophthalmos of exophthalmos and hyperthyroidism group)and healthy controls are statistically difference is compared between(z =-5.07,p < 0.001),they propagated tears of blood in patients with TAO group(including hyperthyroidism exophthalmos of exophthalmos and hyperthyroidism group)and healthy controls are statistically difference is compared between(z =-5.233,p < 0.001).4.The expression of APOC4 in serum was correlated with the level of TSH ?TPOAb?TRAb?TT3?TT4?FT3?FT4(correlation coefficient-0.817,0.7,0.769,0.685,0.725,0.576,0.776,P value < 0.001).There was no significant correlation between the expression of APOC4 and gender,age and smoking.The correlation coefficients were-0.198,-0.0358,0.115,P value 0.208,0.826,0.468 respectively.5.There is a correlation between the expression of APOC4 in tears and TSH,TPOAb,TRAb,TT3,TT4 and FT4 levels(correlation coefficients-0.442,0.774,0.549,0.368,0.593,P were 0.624,0.003,P < 0.001,< 0.001 0.017 < 0.001,< 0.001),and FT3,and gender age,smoking was not significantly correlated(the correlation coefficients were0.228,0.214,-0.181,-0.27,P values were 0.146,0.273,0.251,0.084).6.The expression of ALB in serum was correlated with the levels of TSH,TPOAb,TRAb,TT3,TT4,FT3 and FT4(the correlation coefficients were 0.792,-0.604,-0.717,-0.716,-0.655,-0.725,-0.697,P < 0.001 respectively).There was no significant correlation with sex,age and smoking(the correlation coefficient was 0.02,0.093,0.04,and the p values 0.901,0.559,0.803,respectively).7.The expression of ALB in human blood was correlated with the levels of TSH,TRAb,TT3,TT4,FT3 and FT4(the correlation coefficients 0.817,-0.483,-0.646,-0.49,-0.746,-0.502 respectively,p values 0.003,0.001,<0.001,0.001,<0.001,0.001).There was no significant correlation between TPOAb,sex,age and smoking.The correlation coefficients were 0.026,0.075,-0.077,-0.109 and P,respectively,p=0.87,0.635,0.627,0.491.8.The expression of APOC4 in serum and tear was correlated(correlation coefficient 0.617,P < 0.001).The expression of ALB in serum and tear was correlated(0.535,P < 0.001).Conclusions:1.Similar to serum,APOC4 and serum albumin were to be found and expressed in the tears,this indicates that lacrimal gland acinar cells may be involved in the TAO immune process.2.The correlation between serum albumin and APOC4 expression suggests that their expression in tears may reflect immune changes in the eye.3.Serum and tear serum albumin expression was significantly decreased in TAO patients which suggests a reduction in local antioxidant activity in the eye of TAO patients.It might lead to local oxidative stress and accelerate the progression of inflammation.4.APOC4 level was significantly up-regulation in TAO patients.It indicates that thyroid hormone metabolism not only affect the metabolism,but also has a close relationship with the metabolism of apolipoprotein. |
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