Investigation of the Correlation between Graves’ Ophthalmopathy and CTLA4 Gene Polymorphism
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Abstract:
Graves' disease (GD) is an autoimmune inflammatory disease, and Graves' ophthalmopathy (GO) occurs in 25-50% of patients with GD. Several susceptible genes were identified to be associated with GO in some genetic analysis studies, including the immune regulatory gene CTLA4. We aimed to find out the correlation of CTLA4 gene polymorphism and GO. A total of 42 participants were enrolled in this study, consisting of 22 patients with GO and 20 healthy controls. Chi-square or Fisher's exact test were used to appraise the association between Graves' ophthalmopathy and CTLA4 single nucleotide polymorphisms (SNPs). All regions of CTLA4 including promoter, exon and 3'UTR were investigated. There was no nucleotide substitution in exon 2 and exon 3 of CTLA4 region, and the allele frequencies of CTLA4 polymorphisms had no significant difference between patients with GO and controls. However, the genotype frequency of "TT" genotype in rs733618 significantly differed between patients with GO and healthy controls (OR = 0.421, 95%CI: 0.290-0.611, p = 0.043), and the "CC" and "CT" genotype in rs16840252 were nearly significantly differed in genotype frequency (p = 0.052). Haplotype analysis showed that CTLA4 Crs733618Crs16840252 might increase the risk of GO (OR = 2.375, 95%CI: 1.636-3.448, p = 0.043). In conclusion, CTLA4 Crs733618Crs16840252 was found to be a potential marker for GO, and these haplotypes would be ethnicity-specific. Clinical application of CTLA4 Crs733618Crs16840252 in predicting GO in GD patients may be beneficial.Keywords:
Graves' ophthalmopathy
Genotype frequency
Graves' ophthalmopathy
Genetic predisposition
Gene polymorphism
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Objective To explore the value of serum thyrotrophin receptor antibody (TRAb) on the pathological mechanism of Graves ophthalmopathy.Methods Two hundred and nineteen newly diagnosed Graves disease patients who were divided into Graves ophthalmopathy group (n=121) and without Graves ophthalmolpathy group (n=98) were tested serum concentration with thyroid function,thyroperoxidase antibodies (TPOAb),thyroglobulin antibodies (TgAb) and TRAb.According to the consensus statement of the European Group on Graves ophthalmopathy,clinical activity score (CAS)and severity evaluation were carried out on Graves ophthalmopathy patients.Results There was no significant difference in serum concentration of free thyroxine (FT4),free triiodothyronine (FT3),TPOAb and TRAb between the Graves ophthalmopathy group and the without Graves ophthalmopathy group.Serum concentration of TRAb was not correlated with the severity and CAS of Graves ophthalmopathy.Conclusions The CAS and the severity of Graves ophthalmopathy were irrelevant to the serum concentration of TRAb.Therefore,the correlation between TRAb and Graves ophthalmopathy still needs further study.
Key words:
Graves disease; Graves ophthalmopathy; Thyrotrophin receptor antibody
Trab
Graves' ophthalmopathy
Thyroid peroxidase
Thyrotropin receptor
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Objective To comparison the differences between Graves' ophthalmopathy and ophthalmic Graves' disease,then to provide a method of clinical diagnosis.Methods Clinical Clinical analysis and comparison of 69 Cases of Graves' ophthalmopathy and 38 cases of ophthalmic Graves' disease.Resluts The resluts showed that both diseases had common ocular features of broomsymptom lid retraction,upper lid lag and exophthalmos.Graves' ophthalmopathy tended to be obvious symptoms,occured in binocular,exophthalmos with a longer courselater,but ophthalmic Graves disease patients were more of young people,most with no obvious symptoms,occured in one eye exophthalmos.Triiodothyronine,thyroxine and thyrotropin in patients of ophthalmic Graves' disease were usually in normal common level by laboratory examinations when in Graves' ophthalmopathy patients they were more higher.Conclusion We should give exact diagnosis on Grave's ophthalmopathy by laboratory examinations.Except for Hyperthyroidism,ophthalmic Graves' disease's diagnosis should give X ray and B ultrasonography on orbit to eliminate site occupancy.Clinical doctor should improve recognition on Graves' ophthalmopathy and ophthalmic Graves' disease,to reduce misdiagnosis and missed diagnosis.
Exophthalmos
Graves' ophthalmopathy
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Graves' ophthalmopathy is the most common extra-thyroid manifestation in patients with Graves' disease, based on inflammatory and autoimmune conditions in orbital tissue. This practical guideline was formed by a multidiciplinary team, and is intended to provide guidance for diagnosis and management of Graves' ophthalmopathy in daily clinical practice to improve quality of care and treatment outcome.
Graves' ophthalmopathy
Guideline
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Th1 and Th2-like cytokines are involved in the pathogenesis of Graves' disease. The shift in balance in IL-12/IL-5 cytokines was applied in judging the immunological events in 74 patients with Graves' disease (50 had ophthalmopathy) during methimazole therapy and in 15 controls. The serum levels of IL-12 and IL-5 were measured with enzyme-linked immunosorbent assay in all Graves' patients. Twelve cases for IL-5 and 20 cases for IL-12 were positive. In Graves' patients only those without ophthalmopathy had higher levels of IL-12 when compared to controls (192.66 ± 29.19 vs. 85.09 ± 8.95 pg/ml, P < 0.04). After 2 months of methimazole therapy in Graves' patients without ophthalmopathy an increase in the ratio of IL-12 to IL-5 was also observed as compared to those with eye symptoms (91.78 ± 34.14 vs. 20.72 ± 6.36, P < 0.015). Age-related difference in the serum level of IL-5 could be demonstrated between Graves' patients without and those with ophthalmopathy aged ≤ 35 years (4.89 ± 0.57 vs. 50.14 ± 20.2 pg/ml, P < 0.002). No association was found among the serum levels of IL-5 or IL-12, thyroid hormones and TSH receptor antibodies.The results demonstrated a difference in the balance shift of IL-12/IL-5 between Graves' patients with and without ophthalmopathy. The increased ratio of IL-12 to IL-5 after methimazole therapy could be explained by the elevation of serum IL-12 due to methimazole therapy and the age-related decrease of serum IL-5.
Graves' ophthalmopathy
Methimazole
Pathogenesis
Thyrotropin receptor
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Objective To investigate the significance of detecting serum thyrotropin receptor antibodies(TRAb) in patients with Graves disease or Graves ophthalmopathy.Methods Serum TRAb was measured using radioimmunoassay in 83 patients with Graves disease(group A),73 patients with Graves ophthalmopathy(group B).Patients with Graves ophthalmopathy were assessed using clinical activity score(CAS) and the severity of Graves ophthalmopathy was evaluated using NOSPECS Grade.Results Serum concentration of TRAb was positively correlated with the activity and severity of Graves ophthalmopathy,which was higher in patients with middle and serious Graves ophthalmopathy than that in those with slight Graves ophthalmopathy(P0.05).ConclusionSignificant increase of serum TRAb may be taken as one of the markers to predict the development and guide the treatment in the patients with Graves ophthalmopathy.
Trab
Graves' ophthalmopathy
Clinical Significance
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Graves' disease is the most prevalent cause of hyperthyroidism worldwide. Adiponectin, the most abundant adipokine, plays a significant role in a cluster of prevalent diseases connected to metabolic disorders.Although the association between adiponectin and Graves' disease has been studied, the existing data is inconsistent. Therefore, we conducted this systematic review and meta-analysis to evaluate the relationship between adiponectin levels and Graves' disease.We performed a systematic electronic search on PubMed, EMBASE, Scopus and Cochrane Library using predefined keywords. We used the NHLBI quality assessment tools to assess the included studies.There were 11 studies involving 781 subjects included in our qualitative synthesis, while 6 studies were included in our quantitative synthesis. We observed significantly increased adiponectin levels in Graves' disease patients compared to controls (MD 2.983 [95% CI 0.138-5.828]) and hypothyroidism patients (MD 3.389 [95% CI 1.332-5.446]). Nevertheless, no significant MD was observed when comparing Graves' disease patients with and without Graves' ophthalmopathy (MD -27.124 [95% CI -88.893 - 34.645]).Adiponectin levels were significantly higher in patients with Graves' disease compared to controls and hypothyroidism patients. However, patients with and without Graves' ophthalmopathy did not present a significant mean difference in adiponectin levels.
Graves' ophthalmopathy
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Background: Ophthalmopathy Graves’ is one of the serious complications of Graves’ diseases, that can decrease the quality of life of the patient. The pathogenesis is not well understood, resulting in less effective therapy and resulting in permanent eye function impairment. Objective: To determine the ratio of thyroid stimulating hormone receptor antibody (TRAb) between Graves’ disease patients with and without ophtalmopaty. Methods: This is a cross-sectional study involving 50 patients with Graves’ active disease, who underwent treatment at Endocrine and Metabolic Unit of Internal Disease, Outpatient Installation of Dr. Soetomo General Hospital Surabaya. Graves’ ophthalmopathy was determined when extracted eksoftalmus or eyelid retraction with thyroid dysfunction was found. Levels of thyroid-stimulating hormone (TSH) and FT4 were measured using the ELISA method. Meanwhile, TRAb level was measured using third generation thyroid binding inhibiting immunoglobulins (TBII) with ELISA method. Results: There were 25 (50%) patients in the active Graves’ patient group with and without ophthalmopathy, respectively, with age ranging from 20 to 65 years old. The median value of TRAb patients with Graves ‘disease with ophthalmopathy was 3.21 IU/l, which is higher and statistically significant (p = 0.001) than TRAb levels of patients with Graves’ disease without ophthalmopathy, with median value of 1.81 IU/l. Conclusion: Higher levels of TRAb were found and statistically significant in Graves ‘disease patients with ophthalmopathy than Graves’ patients without ophthalmopathy.
Trab
Graves' ophthalmopathy
Outpatient clinic
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Graves’ ophthalmopathy (GO), also known as thyroid-associated orbitopathy, is the main extrathyroidal manifestation of Graves’ disease.The symptoms of GO range from sore, gritty, and red eyes to do...
Tocilizumab
Graves' ophthalmopathy
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Objective To analyze the correlation between the therapeutic effect of Graves'hyperthyroidism and the outcomes of Graves' ophthalmopathy after 131I therapy,and to explore the effect of 131I treatment on turnout of Graves' ophthalmopathy.Methods Six hundreds and fifty-two patients of Graves' disease accompanied with Graves' ophthalmopathy,received one-time 131I treatment according to routine procedure.We recorded exophthalmometer readings,the signs and symptoms of eyes before therapy.Regular follow-up and appraisal of curative effect were carried out.Results At least six months after 131Itherapy,the effective rate of Graves' hyperthyroidism and Graves' ophthalmopathy were 94.3％ and 73.3％respectively.The total effective rate of hyperthyroidism with ophthalmophy was 71.2％.There was a significant correlation between the prognosis of Graves' ophthalmopathy and therapeutic efficacy of hyperthyroidism (r=0.302,P＜0.05).The outcomes of Graves' ophthalmopathy had no statistically differences between cured and hypothyroidism groups after 131I therapy (x2=0.296,P＞0.05).Conclusions The key to treat Graves' ophthalmopathy is the cure of Graves' hyperthyroidism through 131I therapy.The timely diagnosis and replacement treatment of hypothyroidism can effectively avoid the aggravation of Graves'ophthalmopathy after 131I therapy.
Key words:
Graves ophthalmopathy; Iodine radiosotopes; Drug therapy
Graves' ophthalmopathy
Radioiodine therapy
Antithyroid drugs
Therapeutic effect
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