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Objective:To investigate the serum 25-hydroxyvitamin D [25(OH)D] level in patients with Graves' disease (GD) and its correlation with thyrotropin receptor antibody (TRAb) and bone metabolism markers.Methods:A total of 124 patients with newly diagnosed or relapsed GD were selected and divided into three groups according to serum 25(OH)D level, namely vitamin D deficiency group with 25(OH)D <12 μg/L, vitamin D insufficiency group with 25(OH)D of 12 to 20 μg/L, and vitamin D sufficiency group with 25(OH)D ≥ 20 μg/L. The levels of serum 25(OH)D, TRAb, type I procollagen N-terminal pro-peptide (PINP), type I collagen cross-linked C-terminal peptide (S-CTX), parathyroid hormone (PTH), total triiodothyronine (TT 3), total thyroxine (TT 4) and thyroid-stimulating hormone (TSH) were measured in all patients, and the differences of these biochemical indices were compared across groups. Oneway analysis of variance or Kruskal-Wallis test was used for comparison between groups, and Pearson or Spearman correlation analysis was applied for correlation test. Results:The levels of serum TT 3, TT 4, PINP, and S-CTX significantly increased ( P < 0.01) and the level of phosphorus (P) decreased ( P < 0.01) with the decreased vitamin D levels. The levels of PTH and calcium (Ca) were significantly lower in the vitamin D sufficiency group compared with the vitamin D insufficiency group and vitamin D deficiency group ( P < 0.01). Correlation analysis showed that serum 25(OH)D level was negatively correlated with the levels of TT 3, TT 4, PINP, S-CTX, PTH and Ca ( P < 0.01), and positively correlated with the levels of P and TSH ( P < 0.01). Conclusions:Decreased serum 25(OH)D level is closely related with increased bone turnover, PTH, and thyroid hormone levels in patients with GD, but not related with TRAb. Thyroid hormone levels have a certain predictive value regarding vitamin D deficiency in GD patients. It is necessary to monitor the vitamin D levels in patients with GD and provide vitamin D supplementation to reduce the incidence of osteoporosis, improve the effectiveness of antithyroid treatment and reduce the recurrence of GD.
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Objective:To observe the efficacy of methimazole (MMI) combined with 1α-hydroxyvitamin D3 (alfacalcidol, ALF) in patients with Graves disease of high-titer thyrotropin receptor antibodies (TRAb) and to explore new clinical strategies to reduce serum TRAb in Graves disease.Methods:120 patients with Graves disease initially diagnosed in Quanzhou First Hospital Affiliated to Fujian Medical University and the People′s Hospital Affiliated to Quanzhou Medical College from June 2017 to June 2019 were prospectively selected as the research objects. All patients received conventional dose of MMI for anti hyperthyroidism treatment. The patients were randomly divided into three groups: group A [ n=40, treated with MMI combined with high-dose ALF (0.5 μg/d)], group B [ n=37, treated with MMI combined with low-dose ALF (0.25 μg/d)] and group C ( n=43, treated with MMI only). The treatment lasted for 24 weeks. The serum free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid stimulating hormone (TSH) and TRAb in patients before and after above treatments were detected. The blood routine, liver function, alkaline phosphatase (ALP), 25(OH)D, serum calcium (CA) and serum phosphorus were detected regularly. Results:After drug treatment: ⑴ the thyroid function of the three groups returned to normal. The average daily dosage of MMI in group A was significantly lower than that in group B and C ( P<0.05), and that in group B was also lower than that in group C ( P<0.05), with significant difference. After 24 weeks of treatment, the daily dosage of MMI in group A and B was significantly lower than that in group C ( P<0.05). ⑵ There was no significant difference in thyroid function among the three groups. The concentration of serum TRAb in group A was significantly lower than that in group B and C ( P<0.05), and that in group B was also lower than that in group C ( P<0.05). ⑶ During the 24 week follow-up, there was no significant difference in serum 25(OH)D, ALP, Ca and P among the three groups ( P>0.05); no leukopenia in peripheral blood and no abnormal liver function were found in the three groups. Conclusions:MMI combined with ALF can effectively treat Graves′ disease, reduce the dosage of MMI drugs, decline the level of TRAb in the serum of Graves′ patients, and improve the prognosis of Graves′ disease.
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Objective Higher expression of B-cell activating factor (BAFF) in patients with Graves' disease can activate B cells and increase proportion of plasma cells. However, the mechanism is still unclear. This study aims to investigate the effects of T3 on the BAFF level and plasma cell ratio in bone marrow, spleen and peripheral blood of mice, and to explore the mechanism of T3 in affecting the mature and differentiation of B cells. Methods 80 C57BL/6J mice were randomly divided into control group and T3 group, and were given isotonic saline or T3 5/10μg once a day for 6 weeks, respectively. The levels of T3 in peripheral blood of each group were measured with ELISA. Flow cytometry was used to detect the proportion of B220+CD138+ plasma cells and IgM, IgG and IgD expression of B cells in the spleen, bone marrow and peripheral blood. Immunohistochemistry, Western blot and PCR were performed to determine the expression of BAFF in spleen and thyroid. ELISA was used to determine the expression of BAFF in peripheral blood. Results Compared with control group, the levels of T3 in peripheral blood, diet and drinking water in the T3 group were significantly increased after 6 weeks T3 intervention. The mRNA and protein expression of BAFF in spleen mononuclear cells of T3 group (2.03±0.52, 0.50±0.03) were higher than those in control group (1.06±0.19, 0.05±0.01) (P<0.01). HE staining showed that the white medulla in the spleen of the T3 group increased and merged. Flow cytometry indicated that the proportion of spleen plasma cells and antibody expression of B cells in T3 group [(3.92±1.55)%, (75.76±8.88)%] increased compared with control group [(2.43±1.18)%, (65.26±8.38)%] (P<0.05); Proportion of bone marrow plasma cells [(8.48±3.62)%] and antibody expression [(40.63±18.96)%] in T3 group were significantly increased compared with control group [(4.96±3.11)%, (22.89±7.32)%](P<0.05); Peripheral plasma cell ratio [(8.56±4.27)%] and antibody expression [(76.15±9.44)%] were lower than those in control group [(14.70±4.76)%, (84.20±3.98)%](P<0.05); Compared with control group [(5.98±0.78) pg/mL], the BAFF level in peripheral blood increased [(7.61±1.72) pg/mL] (P<0.01). Immunohistochemistry showed that the expression of BAFF increased in mononuclear cells of thyroid of the T3 group. Conclusion T3 could activate BAFF expression in bone marrow, spleen, peripheral blood and thyroid mononuclear cells, and induce differentiation of bone marrow and spleen B cells, thus causing pathological changes in thyroid tissue. Such mechanisms might play an important role in the pathogenesis of thyroid autoimmune diseases.
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Objective To investigate the detection value of thyrotropin receptor antibody(TRAb)in children with autoimmune thyroid disease.Methods During the January 2015 and October 2016,a total of 72 cases of children with autoimmune thyroid dis-ease admitted to our hospital were selected,including 36 cases of Graves disease as the Graves disease group,and 36 cases of Hashi-moto's thyroiditis as Hashimoto's thyroiditis group;36 cases of healthy children in this hospital at the same period were selected as the control group.Children in the Graves disease group and Hashimoto's thyroiditis group were taken routine treament,ane the changes of the serum TRAb level before the treatment and one year after the treatment between the two groups.The positive value range of TRAb level is more than 1.75 U/L,and the positive rate of serum TRAb level before the treatment and one year after the treatment was recorded in the two groups.Results Before treatment,TRAb level of the Graves disease group[(12.79 ± 6.38)U/L]was higher than those in Hashimoto's thyroiditis group[(2.03 ± 0.29)U/L]and the control group[(0.85 ± 0.23)U/L],and the difference was statistically significant(P<0.05);TRAb level of the Hashimoto's thyroiditis group[(2.03 ± 0.29)U/L]was significantly higher than that of the control group[(0.85 ± 0.23)U/L],(P<0.05).After treatment:TRAb level of the Graves disease group[(9.36 ± 12.14)U/L]was significantly higher than those in Hashimoto's thyroiditis group[(1.78 ± 0.38)U/L]and the control group[(0.84 ± 0.29)IU/L],and the difference was statistically significant(P<0.05);TRAb level of the Hashimoto's thyroiditis group was significantly higher than the control group,and the difference was statistically significant(P<0.05).TRAb levels in patients with graves'disease and Hashimoto thyroiditis after treatment were significantly lower than those before treat-ment,and the difference was statistically significant(P<0.05).The positive rates of TRAb level in the Graves disease group before and after treatment were 100%,and the positive rate of TRAb level in Hashimoto's thyroiditis group after treatment(11.11%)de-creased in comparison with the one before treatment(22.22%),and the difference was statistically significant(P<0.05).Conclusion There is a significant change of TRAb level in children with autoimmune thyroid disease.Especially,the change of TRAb level in Graves disease before and after treatment may provide a reference for clinical diagnosis and prognosis evaluation of Graves disease.
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Objective To analysis the expression of thyroid peroxidase antibody (TPOAb) ,thyroglobulin antibody (TGAb) and thyrotropin receptor antibody (TRAb) in vitiligo patients with different stages .Methods A total of 161 cases of vitiligo patients were divided into advanced group (n=84) and stable group (n=77) according to their condition ,and 60 healthy subjects were cho-sen as the control group .The serum levels of TPOAb ,TGAb and TRAb were detected in 3 groups ,and the difference of the expres-sion level and positive rate between the 3 groups were compared .Results The difference of TPOAb ,TGAb and TRAb levels a-mong the 3 groups was statistically significant (H=14 .371 ,6 .335 ,8 .284 ,P<0 .05) .Multiple comparison showed that :TPOAb , TGAb ,TRAb levels of the advanced group were higher than those of the stable group and the control group (Uvs .stable group =9 .380 , 7 .923 ,8 .381 ,P<0 .05 ;Uvs .control group =23 .244 ,19 .026 ,25 .873 ,P<0 .05);TPOAb ,TGAb ,TRAb levels of the stable group were higher than those of the control group(U=11 .356 ,12 .450 ,16 .351 ,P<0 .05) .The levels of TPOAb ,TGAb and TRAb in the 3 groups were as follows :the advanced group> the stable group> the control group .The positive rates of TPOAb ,TGAb and TRAb in the 3 groups were statistically significant(χ2 =18 .676 ,23 .618 ,23 .857 ,P<0 .05) .Multiple comparison showed that :the positive rates of TPOAb ,TGAb ,TRAb of the advanced group were higher than those of the stable group and the control group (χ2vs .stable group=5 .273 ,6 .484 ,6 .305 ,P< 0 .017;χ2vs .control group = 14 .997 ,18 .352 ,17 .829 ,P< 0 .017);the positive rates of TPOAb , TGAb ,TRAb of the stable group were higher than those of the control group(χ2 =5 .233 ,5 .036 ,6 .719 ,P<0 .017) .The positive rates of TPOAb ,TGAb and TRAb in the 3 groups were as follows :the advanced group> the stable group> the control group .Con-clusion The expression of thyroid autoantibodies (TPOAb ,TGAb ,TRAb) is abnormal in vitiligo patients ,and the progression of the disease is also related to the expression level of such antibodies .
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Objective To analysis the expression of thyroid peroxidase antibody (TPOAb) ,thyroglobulin antibody (TGAb) and thyrotropin receptor antibody (TRAb) in vitiligo patients with different stages .Methods A total of 161 cases of vitiligo patients were divided into advanced group (n=84) and stable group (n=77) according to their condition ,and 60 healthy subjects were cho-sen as the control group .The serum levels of TPOAb ,TGAb and TRAb were detected in 3 groups ,and the difference of the expres-sion level and positive rate between the 3 groups were compared .Results The difference of TPOAb ,TGAb and TRAb levels a-mong the 3 groups was statistically significant (H=14 .371 ,6 .335 ,8 .284 ,P<0 .05) .Multiple comparison showed that :TPOAb , TGAb ,TRAb levels of the advanced group were higher than those of the stable group and the control group (Uvs .stable group =9 .380 , 7 .923 ,8 .381 ,P<0 .05 ;Uvs .control group =23 .244 ,19 .026 ,25 .873 ,P<0 .05);TPOAb ,TGAb ,TRAb levels of the stable group were higher than those of the control group(U=11 .356 ,12 .450 ,16 .351 ,P<0 .05) .The levels of TPOAb ,TGAb and TRAb in the 3 groups were as follows :the advanced group> the stable group> the control group .The positive rates of TPOAb ,TGAb and TRAb in the 3 groups were statistically significant(χ2 =18 .676 ,23 .618 ,23 .857 ,P<0 .05) .Multiple comparison showed that :the positive rates of TPOAb ,TGAb ,TRAb of the advanced group were higher than those of the stable group and the control group (χ2vs .stable group=5 .273 ,6 .484 ,6 .305 ,P< 0 .017;χ2vs .control group = 14 .997 ,18 .352 ,17 .829 ,P< 0 .017);the positive rates of TPOAb , TGAb ,TRAb of the stable group were higher than those of the control group(χ2 =5 .233 ,5 .036 ,6 .719 ,P<0 .017) .The positive rates of TPOAb ,TGAb and TRAb in the 3 groups were as follows :the advanced group> the stable group> the control group .Con-clusion The expression of thyroid autoantibodies (TPOAb ,TGAb ,TRAb) is abnormal in vitiligo patients ,and the progression of the disease is also related to the expression level of such antibodies .
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It has been 50 years since the discovery of thyrotropin receptor autoantibody (TRAb). Advances in the knowledge of thyrotropin receptor ( TSHR) structure and function, combined with the elucidation of TSHR signaling and TSHR-autoantibody interaction have greatly facilitated our understanding of TRAb and their clinical applications. Measurement of TRAb activity plays an important role in the diagnosis of Graves' disease ( GD) and Graves' opthalmopathy. It has also been well recognized that TRAb is an effective predictor of GD relapse or remission after antithyroid drug and radioactive iodine treatment. TRAb test is of particular help in pregnant women and lactating mothers with recent iodine load, where radioactive iodine or technetium tests are contraindicated. In addition, it is useful in the diagnosis and differential diagnosis of fetal and neonatal hyperthyroidism as well as some rare forms of thyrotoxicosis in clinical practice. Accumulating evidence also indicates the possible correlation between thyroid cancer occurring in GD patients with positive TRAb and adverse outcomes. However, further innovation and standardization of TRAb tests are required to help pave the way for clinical applications.
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Objective To explore the relationship of thyrotropin receptor antibody (TRAb) and soluble intercellular adhesion molecule-1 ( sICAM-1 ) in patients with thyroid-associated ophthalmopathy ( TAO), and the role played by TRAb and sICAM-1 in the pathogenesis of TAO. Method Twenty-three TAO patients were assigned to groups according to the clinical activity score and EUGOGO. All patients were treated with intravenous methylprednisolone pulse. The levels of serum TRAb and sICAM-1 were evaluated by a competitive radioimmunoassay and enzyme-linked immunosorbent assay respectively before treatment and by the end of each methylprednisolone pulse. Results The differernce in serum TRAb levels was associated with activity scores of TAO (P=0. 020). The change in serum sICAM-1 was associated with durations of TAO ( P = 0.015). During methylprednisolone treatment in active TAO patients, the levels of TRAb kept on decreasing gradually and markedly declined after the third methylprednisolone pulse in active TAO patients (P＜0.05). The trends of changes in serum TRAb and sICAM-1 levels were both different in active and inactive TAO patients by tendency analysis. Conclusion TRAb level was related to the activity of TAO and might serve as a significant predictor of response to methylprednisolone therapy. The negative correlation between sICAM-1 levels and duration of TAO corroborates the role played by ICAM-1 during the early stage of TAO. Higher sICAM-1 levels are not expected to be specific to TAO and may not predict a response to methylprednisolone therapy.
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Objective:To investigate the association of thyrotropin receptor antibodies(TRAb) with the sensitivity to glucocorticoid therapy in Graves′s ophthalmopathy(GO) patients.Methods:Total 37 subjects with active GO were treated with prednisone. According to the relieve degree and clinical activity of their eye symptoms post-steroid treatment, patients were grouped into sensitive group(S) and non-sensitive group(NS). TRAb positive rate and antibody titer of the two groups were compared.Results:In S group( n=28 ), the positive rate and titre of TRAb were 76.53% and (12.54?5.62) U/L, respectively; The positive rate and titre of TRAb post-treatment were 22.18% and (7.82?4.91) U/L, respectively, were significant lower than data prior treatment. In NS group( n=9 ), the positive rate and titre of TRAb prior treatment were 67.24% and (11.07?4.63) U/L, respectively; The positive rate and titre of TRAb post-treatment were 59.74% and (10.81?5.96) U/L, there was no significant difference with data prior treatment. Prior treatment, there was no significant difference of TRAb titres between the two groups. Post-treatment, TRAb titres in NS group were significant higher than in S group.Conclusion:The variations of TRAb level were closely correlated with the sensitivity to glucocorticoid therapy in GO patients. Serum TRAb level can be used as a major index to evaluate therapeutic sensitivity to glucocorticoid therapy in GO.
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It has been reported that receptor-bound blocking type TSH receptor antibody (TRAb) can be converted to the stimulating type by anti-human IgG antibodies. To evaluate the relationship between the conversion of receptor-bound blocking type TRAb to the stimulating type and the biological activity of blocking type TRAb, we compared converting activities of blocking type TRAb from 10 patients with primary nongoitrous hypothyroidism with both the doses of blocking type TRAb which show 50% inhibition of 125I-bTSH binding to the TSH receptor and those which show 50% inhibition of TSH-stimulated cAMP production in cultured rat thyroid cells (FRTL-5). The additions of anti-human IgG antibody to FRTL-5 cell-bound blocking IgGs resulted in the increase in cAMP production in a dose-dependent manner and the converting activities (percent increase of cAMP production) also depended on the doses of blocking IgGs. The converting activities were significantly correlated with the doses of blocking IgGs which showed 50% inhibition of 125I-bTSH binding to the TSH receptor (r = 0.71, p = 0.011). And these converting activities were also significantly correlated with the doses of blocking IgGs which showed 50% inhibition of TSH-stimulated cAMP increase (r = 0.81, p = 0.002), and were negatively correlated with thyroid stimulation blocking antibody activities (r = 0.58, p = 0.02). We have demonstrated that all cell-bound blocking type TRAb were converted to the stimulating type by anti-human IgG antibody and the degree of conversion was negatively correlated with the biological activity of blocking type TRAb.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Antibodies/immunology , Autoantibodies/immunology , Binding, Competitive , Immunoglobulin G/immunology , Immunoglobulins, Thyroid-Stimulating , Receptors, Thyrotropin/immunology , Thyroid Gland/immunologyABSTRACT
An enzyme immunoassay (EIA) for serum thyrotropin receptor antibodies (TRAb) was described. Polystyrene ball (3.2 mm in diameter) coated with solubilized guinea pig fat cell membranes (SGEM) was incubated with human serum and subsequently with horseradish peroxidase (HRP) conjugated staphylococcus protein A in a total volume of 50 ?I. The HRP activity was measured by spectrophotometer in a micro-cell with 3,3'5, 5'-tetramethylbenzydine (TMB) as substrate and 38 of 40 (95%) untreated Graves'patients (0.28?0.06, X?SD) and 15of 15 (100%) relapsed patients (0.25?0.06) had OD values at least 2 SD above normal subjects (0.09 ? 0.03), P