Change Of IDO In Thyroid Associated Ophthalmopathy And Clinical Value Of Magnetic Resonance Imaging Compared To Ultrasonography

Purpose: Thyroid associated ophthalmopathy (TAO) is a kind of organ specificautoimmune disease. The activated T cell secrete a variety of cytokines, such as tumornecrosis factor and interferon gamma and affect the fibroblasts which play a key rolein the onset of TAO.Indoleamine2,3-dioxygenase(IDO) could maintain peripheralimmune tolerance and regulate immune response through tryptophan metabolism,play an important role in many autoimmune diseases. Expression of IDO in dendriticcells can inhibit T cell proliferation and induction of Treg cells. By studying theamount and IDO expression of dendritic cells in peripheral blood in TAO, number ofTreg cells and IDO expression in orbital tissue, found that IDO differentiallyexpressed in the TAO, Treg cells decline, analysis the effect of IDO in dendritic cellsto T cell, the influence of CTLA-4-Ig on the IDO and explore the role of IDO in thedevelopment of TAO. Orbital ultrasound and magnetic resonance imaging (MRI)examination is the most commonly used diagnosis means in TAO,both of them couldmeasure the thickness of the extraocular muscles.Clinical research contrast the role ofMRI and ultrasound in the sensitivity of eye muscle enlargement,assessment ofdisease and clinical efficacy of patients in TAO.Methods: Collect orbital fatty tissue of TAO patients and the control group,useReal Time PCR and Western blotting and immunohistochemical method to detecttissue IDO mRNA and protein expression changes. Collect peripheral venous blood ofTAO patients and control group, extraction of mononuclear lymphocytes, study theamount of dendritic cells (pDC and mDC) and IDO expression, the number of Tregcells by flow cytometry analysis. Mixed lymphocyte reaction:use the peripheralvenous blood differentiated into dendritic cells in vitro, and CTLA4-Ig stimulusTAO-DCs.Use the immune magnetic bead separation method for CD4+T cells.Thenmake Dendritic cells and CD4+T cell co-culture and use immune fluorescentdyestuff CFSE as CD4+T cells marker. Analysis T cell proliferation by flowcytometry and contrast the effects of different sources of dendritic cells on CD4+Tcell proliferation. To select61cases of TAO,14cases of healthy controls in clinicalresearch.Give patients with eye B ultrasonic and orbital MRI scan, measure thethickness and SIR of the extraocular muscles, measure transverse diameter of lacrimalgland. Analysis the role of ultrasound and MRI in the clinical evaluation of TAO.Results:1.Compared with the control group, the IDO expression decrease indendritic cells in peripheral blood of TAO patients,as to the number of dendritic cells and Treg cells decline.2.In vitro, the expression of IDO in TAO DCs is lower thannormal group, with CTLA4-Ig stimulation can increase the expression of IDO.3.Mixed lymphocyte reaction, the number of CD4+T cell proliferation is higher inTAO group than the control group, CTLA4-Ig stimulus group is lower than withoutstimulate group.4.The muscle thickness of inferior rectus and lateral medial rectusmuscle is relatively larger in MRI than ultrasound, the difference was statisticallysignificant; but there was no statistical difference in superior rectus and medial rectusmuscle thickness.5. MRI measurement of extraocular muscle thickness, ultrasoundmeasurement of extraocular muscle thickness and MRI measuring tear ducts diameterwere significantly associated with CAS score; inferior rectus,superior rectus,medialrectus muscle were significantly related with CAS score. Evaluated the TAO, MRI issuperior to ultrasound.6.To assess clinical anticipated curative effect, combined MRIof extraocular muscle thickness, SIR and lachrymal diameter with maximumsensitivity (100%) and negative predictive value (100%); CAS score with the largestspecificity (85.71%) and positive predictive value (94.59%).Conclusion:1.IDO expression in peripheral blood dendritic cells and orbital fattytissue decreased in TAO patients. The downregulation of IDO expression in TAO canpromote T cell proliferation, inhibit Treg generated,involved in disease development.2. MRI is more sensitive to double enlargement of the inferior rectus muscle, andMRI is superior to B in clinical evaluation and prediction of clinical expected effect ofTAO.MRI could be used to assist the CAS scores to evaluate TAO and predictcurative effect.