Changes of thyroid stimulating antibody and thyroid stimulating blocking antibody in treatment of anti-thyroid drugs and combining with levothyrocine to hyperthyroidism / 中华内分泌代谢杂志

Objective Changes of thyroid stimulating antibody(TSAb) and thyroid stimulating blocking antibody(TSBAb) in the treatment of anti-thyroid drugs(ATDs), and the effect of ATDs combining with levothyrocine(LT4) on TSAb and TSBAb were analyzed. Methods Using recombinant Trxfus. TSHRn protein and Trxfus. TSHRc protein as antigens, and TSH receptor antibody(TRAb)-N(TSAb binding hot spots), TRAb-C(TSBAb binding hot spots)in the serum of thyroid disease patients were measured with ELISA. The changes of TRAb-N, TRAb-C over 36 months in 117 TRAb-N positive Graves′ patients with hyperthyroidism were analyzed retrospectively. In the course of treatment, 41 cases as A group with ATDs and LT4 treatment, 76 cases as B group with only ATDs, The changes of TRAb-N and TRAb-C were observed in the two groups. Results (1)According to the change of TRAb-N, 117 TRAb-N positive Graves′ patients with hyperthyroidism were different. In group Ⅰ, 10 patients continued to have persistently positive TSAb and continued to have hyperthyroidism, remission rate 0%. In group Ⅱ, 17 patients showed complicated TRAb-N changes, 12 of 17 patients got relapse, 5 of 17 patients got remission, remission rate 29.4%. And in group Ⅲ, with TRAb-N dropping gradually, 15 of 89 patients got relapse, 74 of the 89 patients got remission, remission rate 83.1%. Three groups were significantly different with x2 test(P0.05). Conclusion TSAb and TSBAb can be used to document TRAb-function, which is significant for us to predict the changes of thyroid function. During ATDs treatment, the temporary early low-dose application of LT4 did not significantly affect TSAb and TSBAb.

Effects of self-made Yishen Antai Decoction combined with progesterone in the treatment of patients with recurrent spontaneous abortion and the effect on pregnancy outcomes and blocking antibodies / 中国生化药物杂志

Objective To investigate the effects of self-made Yishen Antai Decoction combined with progesterone in the treatment of recurrent spontaneous abortion (RSA) and the effect on pregnancy outcomes and blocking antibodies (BA). Methods 100 cases of patients with RSA were randomly divided into the observation group and the control group, 50 cases in each group. The control group was treated with progesterone and on the basis, the observation group was additionally treated with self-made Yishen Antai Decoction. Both groups were intervened till 12 weeks of gestation, and the clinical curative effect was evaluated. Results The total effective rate of treatment, the success rate of pregnancy and the positive rate of blocking antibody (BA) showed significant differences between the observation group and the control group (P< 0.05). After treatment, the total TCM symptom score and serum levels of interleukin-2 (IL-2) and interferon-γ (IFN-γ) were significantly lower while interleukin-10 (IL-10) level was significantly higher in the observation group than the control group (P< 0.05). There were no serious adverse reactions in the two groups. Conclusion Self-made Yishen Antai Decoction is effective and safe in the treatment of RSA. It can significantly improve the success rate of pregnancy and the positive rate of BA, which may be associated with the regulation of IL-2, IL-10 and IFN-γ levels.

A baby with congenital hypothyroidism born to a hypothyroid mother who expressed undiagnosed thyroid stimulation blocking antibody

In adults, hypothyroidism caused by thyroid stimulation blocking antibody (TSB Ab) is rare, and confirmed cases are even fewer, as TSB Ab levels are rarely assayed. However, this may create problems in babies, as the transplacental passage of maternal TSB Ab can cause a rare type of hypothyroidism in the infant. Prompt levothyroxine replacement for the baby starting immediately after birth is important. We describe a congenital hypothyroid baby born to a hypothyroid mother who was not aware of the cause of her hypothyroid condition, which turned out to be associated with the expression of TSB Ab. This cause was confirmed in both the infant and mother using a series of thyroid function tests and measurements of autoantibody levels, including TSB Ab. During periodic follow-up, the TSB Ab and thyroid stimulating hormone receptor antibody titers became negative in the baby at 8 months of age, but remained positive in the mother. Evaluation of hypothyroidism and its cause in mothers during pregnancy is important for both maternal and child health.

A baby with congenital hypothyroidism born to a hypothyroid mother who expressed undiagnosed thyroid stimulation blocking antibody

In adults, hypothyroidism caused by thyroid stimulation blocking antibody (TSB Ab) is rare, and confirmed cases are even fewer, as TSB Ab levels are rarely assayed. However, this may create problems in babies, as the transplacental passage of maternal TSB Ab can cause a rare type of hypothyroidism in the infant. Prompt levothyroxine replacement for the baby starting immediately after birth is important. We describe a congenital hypothyroid baby born to a hypothyroid mother who was not aware of the cause of her hypothyroid condition, which turned out to be associated with the expression of TSB Ab. This cause was confirmed in both the infant and mother using a series of thyroid function tests and measurements of autoantibody levels, including TSB Ab. During periodic follow-up, the TSB Ab and thyroid stimulating hormone receptor antibody titers became negative in the baby at 8 months of age, but remained positive in the mother. Evaluation of hypothyroidism and its cause in mothers during pregnancy is important for both maternal and child health.

Clinical Observation of Habitual Abortion Patients Treated by Yishen Tianjing Zhuyun Prescription Together with Active Lymphocyte Immunotherapy / 广州中医药大学学报

Objective To investigate the therapeutic effect of Yishen Tianjing Zhuyun Prescription(a Chinese herbal recipe consisting of Xianqi Yizhen Capsules and Xianzi Yizhen Capsules, having the actions of strengthening kidney-essence and promoting gestation) together with active lymphocyte immunotherapy for habitual abortion (HA)patients. Methods A total of 139 HA outpatients with negative blocking antibodies(BA)were randomly divided into treatment group(70 cases) and control group(69 cases). The control group was treated only with active lymphocyte immunotherapy, while the treatment group was treated with Yishen Tianjing Zhuyun Prescription and active lymphocyte immunotherapy . Results (1) After treatment, the BA-positive rate was 82.86% in the treatment group and was 60.87% in control group, and there existed significant difference between the two groups (P < 0.05 ). (2) The total anti-abortion effective rate was 87.14% in the treatment group and was 66.67% in control group, the difference being significant between the two groups(P<0.05 ). Conclusion Yishen Tianjing Zhuyun Prescription combined with active lymphocyte immunotherapy is more effective than active lymphocyte immunotherapy alone for the treatment of HA patients with negative BA.

Significance of thyroid stimulating antibody and thyroid stimulating-blocking antibody in children with autoimmune thyroid disease / 中华实用儿科临床杂志

Objective To study the significance of thyroid stimulating antibody (TSAb) and thyroid stimulating-blocking antibody (TSBAb) in children with Graves' disease (GD) or Hashimoto's thyroiditis (HT).Methods Five hundred and twenty-seven cases of serum from 180 children with autoimmune thyroid disease (AITD) children were divided into 282 cases of GD and 245 cases of HT.According to the status of thyroid function,they were divided into 157 cases of hyperthyroidism,91 cases of hypothyroidism and 279 cases of normal thyroid.GD group was subdivided into 127 GD hyperthyroidism and 155 GD remission;HT group was subdivided 30 HT hyperthyroidism,124 HT remission and 91 HT hypothyroidism.Seventy-nine healthy children were taken as the healthy control group.Free triiodothyronine(FT3),free thyroxine(FT4) and sensitive thyroid stimulating hormone(TSH) were detected by chemoluminescence.Serum TSAb and TSBAb were detected by serum TSAb or TSBAb enzyme linked immunosorbent assay (ELISA),respectively.The differences in TSAb and TSBAb among each group were compared and analyzed of find out the relationship between TSAb and TSBAb was performed.Beside,the correlation between TSAb and TSBAb with FT3,FT4,and TSH were analyzed.Results (1) TSAb levels were significant (F =11.995,all P =0.000):the GD group (0.727 ± 0.157) ＞ HT group (0.605 ± 0.148) ＞ healthy control group (0.350 ± 0.105);the difference was significant(F =109.165,P =0.000) among hyperthyroidism group (0.745 ± 0.169) ＞ normal thyroid group (0.647 ± 0.153) ＞hypothyroidism group(0.612 ±0.144) ＞healthy control group (0.350 ±0.105);the difference was significant(F=156.712,P =0.000) in the GD hyperthyroidism group(0.747 ±0.17) ＞ GD remission group (0.640 ± 0.16) ＞ healthy control group (0.350 ± 0.105);the difference was significant (F =109.165,P =0.000) in the HT hyperthyroidism group(0.739 ±0.140) ＞HT remission group(0.655 ±0.135) ＞ HT hypothyroidism group(0.612 ± 0.140) ＞healthy control group (0.350 ±0.105).(2) TSBAb levels were significantly different(F =15.610,P =0.000):the HT group(0.704 ±0.633) ＞ GD group(0.567 ±0.178) ＞ healthy control group (0.334 ±0.104);the difference was significant(F =13.311,P =0.000) in the hypothyroidism group (0.693 ± 0.125) ＞ remission group (0.648 ±0.446) ＞hyperthyroidism group(0.562 ±0.181) ＞healthy control group(0.334 ±0.104);the difference was significant(F =19.269,P =0.000) in the GD remission group (0.672 ±0.572) ＞ GD hyperthyroidism group (0.550 ± 0.187) ＞ healthy control group (0.334 ± 0.104);HT hypothyroidism group (0.693 ± 0.725) was higher than HT hyperthyroidism group(0.618 ±0.142) and HT remission group (0.619 ±0.199),the difference was not significant between HT hyperthyroidism group and HT remission group(F =12.208,P =0.000).(3) TSAb level was positively correlated with TSBAb,FT3 and FT4(r =0.162,0.091,0.194,all P ＜ 0.05) and was negatively correlated with TSH (r =-0.224,P ＜ 0.05).TSBAb levels were negatively correlated with FT3 (r =-0.155,P ＜ 0.05) and was positively correlated with TSH (r =0.131,P ＜ 0.05).Conclusions Thyroid function was related to the serum levels of TSAb and TSBAb.TSAb and TSBAb could be regarded as an important predictive index for children with AITD during the treatment period.

The early changes of humoral immune response after rush immunotherapy with Dermatophagoides farinae (D.f) and Dermatophagoides pteronyssinus (D.p) in house dust mite sensitive asthmatic children / 천식및알레르기

PURPOSE: Rush immunotherapy (RIT) with house dust mite may be effective to treat house dust mite allergic disease, but the mechanisms are not clear. Considerable attention has been devoted to the IgG subclass in relation to clinical outcome. Usually, conventional immunotherapy with D.f and D.p is followed early on by a rise in allergen-specific IgG1 with a gradual decline over time and slow rise in allergen-specific IgG4. Some investigators have implicated that IgG4 is a more important blocking antibody than IgG1 in RIT. But there is no consistent data on the early changes of allergen-specific IgG1 or IgG4. To inves- tigate the alteration of humoral immunity in the mechanism of early phase of RIT, the D.f -specific IgE, IgG1, and IgG4 levels of the RIT group were compared with that of the con- trol group with asthma. METHOD: The RIT group included 17 D.f and D.p-sensitized asthmatic children, who had received RIT with D.f and D.p, and the control group included 15 D.f and D.p-sensitized asthmatic children who had not received RIT. They received RIT to mite for just over 8 weeks until maintenance was achieved. The symptom scores of asthma, skin reactivity to D.f (allergen/histamine ratio), RIT changes of D.f-specific IgE, IgG1, and IgG4 levels were compared before and 8 weeks after for the two groups. D.f-specific IgE, IgG1, and IgG4 levels were measured by ELISA. RESULTS: The symptom scores and the skin reactivity to D.f decreased significantly 8 weeks after RIT. D.f-specific IgG1 levels increased significantly 8 weeks after RIT in the RIT group but not in the control group. But D.f-specific IgE and D.f- specific IgG4 levels did not change 8 weeks after RIT in either of the two groups. CONCLUSION: D.f-specific IgG1 production was increased in the early phase of RIT. These findings suggest that the early clinical changes after RIT may be linked to the early increase of IgG1 blocking antibody.

Changes in Properties of Thyrotropin Receptor Antibodies Following Radioiodine Treatment in Patients with Graves' Disease / 대한내분비학회지

BACKGROUND: It has been suggested that thyroid stimulation blocking antibody (TSBAb) is involved in the development of early hypothyroidism after radioiodine treatment in patient with Graves disease. However, previous studies have reported the effect of radioiodine treatment on overall changes of TSH receptor antibodies without detailed observation of changes in properties of TSH receptor antibodies. The aim of this study is to evaluate the effect of radioiodine treatment on thyroid stimulation antibody (TSAb) or on thyroid stimulation blocking antibody (TSBAb) activities and to see whether the appearance of TSBAb after radioiodine treatment is involved in the development of early hypothyroidism in patients with Graves disease. METHODS: The activities of TSAb, TSBAb were measured serially with human TSH receptor transfected Chinese hamster ovary (CHO) cells in 36 patients with Graves disease who received 131I treatment. In addition to the wild type TSH receptor-expressing cells, we used a chimeric receptor that 90-165 amino acid residues were substituted by those of rat LH/CG receptor (Mc2) for measurement of TSBAb without interference by the presence of TSAb and for evaluation of TSAb epitope spreading. We evaluated the association of early hypothyroidism after 131I treatment with changes of various immunologic parameters. RESULTS: In 14 (39%) of 36 patients, TSBAb activities were present in their sera before or after 131I treatment. Four of them had TSBAb activities before 131 treatment, and 12 newly acquired TSBAb activities after 131I treatment. The existence of TSBAb was not associated with the development of early hypothyroidism after 131I treatment but with low TSAb activities before 131 treatment, high thyroidal uptake of 131I given and with old age. The phenomena of epitope spreading measured by TSAb with Mc2 mutant clone before and after 131I treatment was not infrequent, but it had no clinical relevance. CONCLUSION: These results suggest that the existence of TSBAb may be not a major factor in the development of early hypothyroidism after radioiodine treatment in Graves disease. Other factors such as TSAb activities before radioiodine treatment, the efficiency of thyroidal uptake of 131I or old age are associated with the development of early hypothyroidism.

Measurements of Thyroid Stimulation Blocking Antibody Activities by Chinese Hamster Ovary ( CHO ) cells Expressing Human TSH Receptors in Patients with Primary Hypothyroidism / 대한내분비학회지

BACKGROUND: The Chinese hamster ovary cells transfected with human TSH receptor cDNA (hTSHR-CHO), expressing functional human TSH receptors, are known to be more sensitive in detection of thyroid stimulating antibodies than FRTL-5 cells. There has been no report on the usefulness of these cells to measure thyroid stimulation blocking antibody (TSBAb) activity which is frequently found in patients with primary myxedema, METHODS: We established the optimal assay condition of measurement of TSBAb using hTSHR-CHO cells, and simultaneously measured TSBAb activities with FRTL-5 cells and with hTSHR-CHO cells in 49 patients with primary myxedema, compared them with their thyrotropin binding inhibitor immunoglobulin (TBII) activities. RESULTS: 1) hTSHR-CHO cells specifically bound bTSH and were stimulated by bTSH in terms of cyclic AMP generation in a dose dependent manner. 2) Myxedema IgG suppressed TSH-stimulated cAMP production of hTSHR-CHO cells in a dose dependent manner reaching plateau at the concentration of I g/L. Normal pooled IgG has no suppressive action at the concentration of less than 1 g/L, but caused significant suppression at the concentration of greater than 1g/L. 3) TSBAb activities measured by hTSHR-CHO cells in 49 patients with primary myxedema were as follows: Four of 25 TBII-negative cases (16%) and 22 of 24 TBII-positive cases (92%) had TSBAb activities. Most of TSBAb positive patients (95%), especially in TBII positive cases, showed very high activities of more than 90%. 4) TSBAb activities measured by hTSHR-CHO cells and those by FRTL-5 cells were both positive in 24 patients (49%), both negative in 18 patients (37%), and were discrepant in 7 patients (14%). The TSBAb activities measured with hTSHR-CHO cells and those measured with FRTL-5 cells were significantly correlated (r=0.71, p< 0.01). 5) Forty five percent of patients with primary myxedema had all of 3 kinds of activities (TBII, hTSHR-CHO cell TSBAb, FRTL-5 cell TSBAb), 37% of them had none of 3 activities and 18% of them had 1 or 2 kinds of activities only. CONCLUSION: The usefulness of hTSHR-CHO cells in measurements of TSBAb activities were confirmed. The TSBAb activities of most patients with primary myxedema measured by hTSHR-CHO cells were concordant with those measured by FRTL-5 cells. However, a small subset of patients (18%) had discrepant results in assays of TSH receptor antibodies according to the differences in TSH receptors (rat, human and porcine) used in assay. Such discrepancy may be explained by heterogeneity in epitopes for blocking TSH receptor antibodies.

Clinical Significance and Immunological Characteristics of Blocking TSH Receptor Antibodies in Patients with Hashimoto's Thyroiditis / 대한내분비학회지

BACKGROUND: TSH receptor blocking antibody (TRBAb) is a pathogenic factor in the vast majority of patients with primary myxedema. It has been reported that TRBAbs are found in some patients with chronic goitrous autoimmune thyroiditis (Hashimoto's thyroiditis), but the significance or the role of TRBAb in Hashimotos thyroiditis is not clear, We recently reported that hTSHR-CHO cells which express the functional human TSH receptors are more sensitive and are better in detecting functional TSH receptor antibodies in Graves patients than FRTL-5 cells. We are to investigate the biological role of TRBAb in Hashimotos thyroiditis by measuring thyroid stimulation blocking antibody (TSBAb) activities of Hashimoto's IgG's using hTSHR-CHO cells. Moreover, we are to see if there is any difference in epitope recognition between Hashimotos TRBAb and myxedema's TRBAb by measuring TSBAb activities with mutant receptor expressing cell lines, Mcl+2 and Mc 2 in those patients. METHOD: We measured TSBAb activities of IgGs from patients with primary myxedema (PM, n= 10) and those with hypothyroid (n 20) or euthyroid (n 17) Hashimoto's thyroiditis (HT) using wild type hTSHR-CHO cells (WT) and two chimeric receptor expressing cell lines, Mcl+2 and Mc2. RESULTS: TSBAb activities measured by WT were higher in hypothyroid HT than in euthyroid HT (30.0+-23.2% vs. 6.1+-28.7, p<0.05), and TSBAb-positive rate tend to be higher in the former (20%, 5/20) than in the latter (0%, 0/17, p=0.07). TRBAbs from PM (n=4) had high TBII activities and had persistent blocking activities despite of the replacement of amino acid residue 8~165 of extracellular domain of TSHR with those of rat LH/CGR (Mcl +2). However, TRBAbs from HT (n=4) had no TBII activity at all and lost blocking activities when measured with Mcl+2. CONCLUSION: TRBAbs are found in 20% of hypothyroid patients with Hashimotos thyroiditis in assay using hTSHR-CHO cells, and they seem to play a role in the development of hypothyroidism in some patients with Hashimotos thyroiditis. TRBAbs of Hashimotos thyroiditis are different in epitope recognition from TRBAbs of primary myxedema.

STUDY OF SERUM TRAb IN AUTOIMMUNE THYROID DISEASE WITH ABC- ELISA / 西安交通大学学报(医学版)

In this paper the investigation of using a new method-ABC-ELISA in assay of Autoimmune Thyroid Disease are presented. The sensitivity of ABC-ELISA is compared with that of standard ELISA; Its reliability is proven by the methods of detecting TSAb with FRTL-5. TRAb is detected by ABC-ELISA in 91% of untreated Graves'. TRAb is detected by Standard ELISA in 70% of untreated Graves'. The results of ABC-ELISA in 26 untreated Graves' are equal to that of the method of detecting TSAb with FRTL-5. Therefore, we consider that ABC-ELISA is a sensitive, reproducible, convenient method applicable to clinical practice.