| BackgroundThyroid associated ophthalmopathy is an inflammatory process in theorbital associated with thyroid autoimmune,it is one of the most commonorbital disease.The clinical manifestation of TAO is various.Patients withTAO can have ocular surface discomfort, such as excess tearing,increased sensitivity to light, upper eyelid retraction. Some seriousmanifestation include diplopia, unilateral or bilateral exophthalmos,vision loss and even blindness and other symptoms. Thyroid function ofTAO can be expressed as hyperthyroidism, euthyroidism orhypothyroidism. The pathogenesis of TAO is complicated andcontroversial, the argument is more recognized that TAO is anautoimmune disease. Thyroid stimulating hormone receptor(TSHR) playsan important role in TAO occurrence and development, so far, thyrotropinreceptor antibody(TRAb) is considered to play a certain role in indicatingTAO recurrence risk and prognosis evaluation. Thyroid peroxidase(TPO)is the key enzyme during thyroid hormones synthesis. In normalcondition, it is expressed on thyroid follicular cells, but it was releasedinto the blood when thyroid follicular cells were destroyed, this processcan induce thyroid peroxidase antibody producing and cause a series ofimmune responses.TPOAb expression in autoimmune thyroid disease issignificantly higher than in other thyroid function abnormalities, it can be considered as autoimmune disease biomarker and prognosis indicators.But a large scale of clinical observations show that TAO ocularmanifestations are not completely parallel with the level of serumTRAb, or even has the opposite manifestations. Therefore, whether thelevel of serum TRAb can be judged as criteria of TAO remainscontroversial.TAO is a multisystem inflammatory disease. As component of localimmune system, larcrimal gland may be involved in the occurrence anddevelopment of TAO. Lymphocytes infiltration in larcrimal gland werefound in TAO patients, cytokines produced by these lymphocytes canpromote orbital inflammatory response. In addition, orbital fibroblastsexpress multiple enzymes involved in the biosynthesis of theglycosaminoglycans(GAG) as well as hyaluronan, a large amount ofGAG and hyaluronan was produced secondary by cytokines production,which resulted in increased lacrimal gland volume and orbital edema,these are consistent with imaging performance of TAO patient’s lacrimalgland. TSHR can expressed on thyroid follicular cells as well as lacrimalacinar cells, this cross antigen may be involved in the immune responseprocess of TAO. Tear was secreted by lacrimal gland and can lubricationocular surface, providing nutrients and involving in immune defense.Immune active ingredient and lymphocytes infiltrated in orbital tissuewhich can induce cytokines producing and involve in the local inflammatory response. Lacrimal gland can express TSHR, indicatingTRAb might express in tear, and tear TRAb expression may be muchmore involved in orbital immune than serum TRAb expression.Meanwhile, TPOAb can reach orbital tissue and lacrimal gland throughblood circulation and cause ocular surface damage. Until now there arevery few studies about antibody expression in tears, antibodies in tear ofTAO patients and healthy populations are still unclear. Studying onassociated antibody expression in tear can help to explore the role oflacrimal gland in occurrence and development of TAO, to find newbiomarkers and clinical therapeutic effect indicators for TAO. In addition,tear collecting in this study is non-invasive method which and can beeasily accepted by TAO patients.ObjectiveTo characterize the expression of TRAb and TPOAb in tears of TAOpatients and healthy controls, looking for more accurate markers andpotential therapeutic targets for TAO.Materials and methods42patients with autoimmune thyroid disease who admittedhospitalization and outpatient treatment in our hospital from July2013toFebruary2014were recruited. The general information and clinical data,eye condition(according to Clinical activity score(CAS,Mourits,1989)and Classification standard of Graves eye disease(ATA,1997)) were collected.34healthy controls were recruited, who have no autoimmunedisease history, thyroid disease history or family history were excluded,mean age of the controls is28.09±6.17years. Informed consent wassigned before blood and tear sample were collected. Serum and tearsample were collected and frozen at-80℃. TPOAb and TRAb levelswere tested by radioimmunoassay. All experimental data were analyzedstatistically.Results1. TPOAb and TRAb expression in serum and tear were significantdifferent between TAO patients and healthy controls(t=2.888,2.888,2.288,3.349,p=0.000,0.002,0.002,0.007).2. TPOAb and TRAb level in both serum and tear of TAO patientswere higher than in control group.3. In TAO patients group, serum and tear TPOAb expression weremoderately correlated (r=0.640,p <0.001).Serum and tear TRAbexpression had mild correlation(r=0.264,p=0.027).4. TAO patients were grouped into four subgroup according to the CAS,both TPOAb and TRAb expression in serum and tear among thesubgroups had no significant difference.Conclusions1. Similar to serology, TPOAb and TRAb do expressed in tear,which combined with imaging and pathology studies, indicated lacrimal acinar cells may participate in immune process of TAO.2. TPOAb and TRAb expression were different between serum andtear indicated that there were some biomarker in tear, which could beused for TAO diagnosis.3. The correlation between serum TPOAb and tear TPOAb alongwith the correlation between serum TRAb and tear TRAb indicated thatthese biomarkers expression in tear can reflect local immune in eye.4. The group size of this study is limited, so a large scale ofrecruitment is needed in the following studies besides that smokingcontrol group is also need to be included. |
PDF Full Text Request