不同类型甲状腺疾病患者可溶性细胞间黏附分子-1变化及临床意义

目的探讨不同类型甲状腺疾病患者可溶性细胞间黏附分子-1(sICAM-1)变化及临床意义。方法选择初诊甲状腺疾病患者137例,其中Graves病(GD)69例(GD组)[伴Graves眼病(GO)20例],桥本甲状腺炎(HT)35例(HT组),单纯性甲状腺肿(SG)20例(SG组),非毒性结节性甲状腺肿(NTNG)13例(NTNG组)。另选健康查体者277例作为对照组。采用125I-sICAM-1 RIA方法检测各组血清sICAM-1,化学发光法检测FT3、FT4、sTSH,放免法检测甲状腺球蛋白抗体(TGAb)、甲状腺微粒体抗体(TMAb),ELISA法检测促甲状腺素受体抗体(TRAb)、甲状腺刺激免疫球蛋白(TSI);采用Spearman等级相关分析,分析sICAM-1与甲状腺功能及甲状腺自身抗体指标的相关性。结果与对照组比较,GD组、HT组sICAM-1明显升高(P均<0.01),GD组与HT组、SG组与NTNG组比较,P均>0.05;GO患者的sICAM-1明显高于非GO患者(P<0.05)。GD组sICAM-1与FT3、FT4呈正相关(r分别为0.467、0.441,P均<0.05),与TRAb、TSI、TGAb、TMAb无明显相关性(P均>0.05)。结论血清sI-CAM-1可作为免疫指标之一,辅助诊断GD、HT等甲状腺疾病。     

血清25羟-维生素D、碘营养状况与自身免疫性甲状腺病的相关性

目的探讨25羟-维生素D[25(OH)D]水平、碘营养状况和自身免疫性甲状腺疾病(AITD)的相关性。方法通过检测380例粤中西部地区居民的空腹血清25(OH)D水平、甲状腺功能、甲状腺自身抗体、尿碘等相关指标等,并比较25(OH)D缺乏患者治疗后相关指标的差异,分析血清25(OH)D、碘营养状况对AITD发病的影响。结果 Graves病(GD)组、桥本甲状腺炎(HT)组25(OH)D3水平显著低于健康对照组(P<0.05)。GD组血清25(OH)D3水平与促甲状腺激素受体抗体(TRAb)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)呈显著负相关,与促甲状腺激素(TSH)呈显著正相关(P<0.01,P<0.05)。HT组血清25(OH)D3水平与抗甲状腺球蛋白抗体(TGAb)、抗甲状腺过氧化物酶抗体(TPOAb)、TSH呈显著负相关,与FT3、FT4呈显著正相关(P<0.01,P<0.05)。在GD组应用甲巯咪唑和HT组应用左甲状腺素的基础上加用活性维生素D连续治疗3个月后,GD组TRAb抗体水平明显降低,HT组TGAb、TPOAb抗体水平也明显降低(均P<0.05)。GD组和HT组尿碘中位数均较对照组高。尿碘高的AITD患者25(OH)D3水平缺乏更明显(P<0.05)。结论 AITD初发患者伴低维生素D水平,其中尿碘高的AITD患者25(OH)D3水平缺乏更明显。补充活性维生素D可降低其自身抗体水平。     

初发Graves病患者血清促甲状腺激素受体抗体水平的影响因素分析

目的分析初发Graves病(GD)患者体内促甲状腺激素受体抗体(TRAb)水平的影响因素。方法初发GD患者378例,采用酶联免疫吸附测定法检测患者血清TRAb,化学发光法检测血清甲状腺过氧化酶抗体(TPOAb)、甲状腺球蛋白抗体(TGAb)、游离甲状腺素(FT4)、游离三碘甲状腺原氨酸(FT3)和促甲状腺激素(TSH)。采用多元逐步回归分析法,以TRAb为应变量,以患者年龄、性别、病程、甲状腺质量、TGAb、TPOAb、是否突眼、FT3、FT4和TSH为自变量建立回归方程。结果甲状腺质量及合并Graves眼病(GO)与初发GD患者体内TRAb水平相关。结论甲状腺质量及合并GO是初发Graves病患者体内TRAb水平的影响因素。     

血清TRAb水平与Graves病患者131I治疗后早发甲减的关系

目的探讨血清促甲状腺激素受体抗体(TRAb)水平在Graves病(GD)患者131I治疗后早发甲状腺功能减低(甲减)发生中的作用,为临床随访监测提供依据。方法将123例GD患者按治疗前血清TRAb水平分为TRAb阳性组(TRAb>15 IU/mL)和TRAb阴性组(TRAb≤15 IU/mL),分别于131I治疗前及治疗后3、6、12个月测定血清游离三碘甲状腺原氨酸(FT3)、游离四碘甲状腺原氨酸(FT4)、促甲状腺激素(TSH)水平,并判定早发甲减发生情况。结果 TRAb阳性组和TRAb阴性组早发甲减率分别为54.72%(29/53)、31.43%(22/70),两组比较P<0.05。结论血清TRAb水平在GD患者131I治疗后早发甲减发生中起重要作用,临床可据此采取相关防治措施。     

Graves病患者131I治愈前后尿微量蛋白的变化观察

目的：探讨Graves病（简称GD）患者131 I治愈前后尿微量蛋白变化的影响因素。方法选择GD患者20例（GD组）,根据131I治愈前后分成治疗前的GD组、治愈3个月R3M组、治愈12个月R12M组,并设正常对照组20例。采用全自动化学免疫发光法检测血清游离甲功3项[包括游离三碘甲状腺原氨酸（ FT3）、游离甲状腺素（ FT4）、促甲状腺素（ TSH）]、促甲状腺受体抗体（ TRAb）、尿微量白蛋白（ Alb）、尿免疫球蛋白（IgG）、尿微球蛋白（β2-MG）含量。采用散射比浊法检测血清中超敏C反应蛋白（hs-CRP）。全自动血凝仪测定血清D-二聚体（ D-D）。 SPECT计算总肾小球滤过率（ TRGFR）。结果 GD组游离甲功3项与各组比较差异有统计学意义（ P＜0.01）。 GD组、R3M组的TRAb、Alb、IgG与其余组比较差异有统计学意义（ P＜0.01）。直线相关分析显示,FT3与Alb、IgG呈显著正相关（ r分别为0.64、0.72, P均＜0.01）, TRAb与Alb、IgG呈显著正相关（ r分别为0.66、0.56,P均＜0.01）。结论 GD肾损害的部位在肾小球,与免疫紊乱关系密切;GD相关抗体的消失可作为判断GD肾损害的恢复及治疗效果的参考指标。     

尿碘与甲状腺疾病相关性的研究

目的 探讨尿碘与甲状腺疾病的关系.方法 采用病例对照研究的方法,选取2011、2012年在山西省地方病防治研究所附属医院就诊的甲状腺疾病患者109例作为病例组,并将患者分为Graves病组(GD组,48人),慢性淋巴细胞性甲状腺炎组(HT组,34人)和甲状腺结节组(27人),同时选取本地区62例健康人群作为对照组.采用砷铈催化分光光度法测定尿碘,电化学发光法检测血清促甲状腺激素受体抗体(TRAb)、抗甲状腺过氧化酶抗体(TPOAb),甲功仪测定吸碘率,B超法测定甲状腺体积,分析各组患者尿碘水平与甲状腺疾病的关系.结果 GD组、HT组、甲状腺结节组和对照组的尿碘中位数分别为:313.95、375.20、220.20、196.50 μg/L,GD组和HT组均高于对照组(Z值分别为3.238、4.275,P均＜0.0125);HT组和甲状腺结节组比较差异有统计学意义(Z=3.762,P＜ 0.0125).GD组、HT组、甲状腺结节组和对照组的吸碘率分别为(84.20±16.90)％、(23.51±6.72)％、(28.34±8.02)％、(29.31±8.41)％;TRAb分别为(58.57±20.31)％、(2.54±1.00)％、(2.98±0.83)％、(3.01±1.21)％; TPOAb分别为(117.03±57.21)％、(251.00±98.20)％、(16.81±9.87)％、(15.00±7.23)％.GD组吸碘率、TPOAb与TRAb均高于对照组(P均＜0.05),HT组的TPOAb高于对照组(P＜0.05).GD组与HT组的尿碘水平与TPOAb正相关(相关系数分别为0.462、0.478,P均＜0.05).结论 Graves病与慢性淋巴细胞性甲状腺炎患者存在碘过量摄入.尿碘测定有助于个体化补碘.     

小剂量甲状腺素治疗能减少Graves病的复发吗?

观察单用抗甲状腺药物 (ATD)治疗组与ATD联合小剂量甲状腺素治疗组之间Graves病(GD)复发率。结果显示两组治疗结束时临床表现、甲状腺功能、TSH受体抗体 (TRAb)阳性率均相似 ,停药 1年GD复发率差异无显著性 ,但复发者甲状腺肿较严重、突眼率较高以及TRAb阳性率较高 (均P <0 .0 1)。     

Graves病甲状腺功能亢进症性肝损害的相关因素分析

目的 探讨影响Graves病甲状腺功能亢进症(甲亢)性肝功能损害的相关因素.方法 回顾性分析天津医科大学总医院2013年1月至2015年12月收治的Graves病住院患者254例,根据肝功能将患者分为Graves病甲亢性肝损害组(A组,n=159)和甲亢肝功能正常组(B组,n=95),比较两组的基础代谢率(BMR)、甲状腺重量、FT3、FT4、促甲状腺激素(TSH)、TSH受体抗体(TRAb)、甲状腺球蛋白抗体(TgAb)、甲状腺过氧化物酶抗体(TPOAb).采用Pearson相关性分析甲状腺重量、BMR、FT3、FT4、TRAb与甲亢性肝损害的相关性,应用Logistic回归分析甲亢性肝损害的独立危险因素.结果 A组的甲状腺重量、BMR、FT3、FT4、TRAb、TPOAb均高于B组,而TSH低于B组(t或z=-4.720～-2.276,P均＜0.05).Pearson相关性分析显示,甲状腺重量、BMR、FT3、FT4、TRAb与甲亢性肝损害的发生呈正相关(r=0.157～ 0.270,P均＜0.05).Logistic回归分析显示,FT3(OR=1.052,95％ CI:1.001～1.105)、BMR(OR=1.019,9.5％ CI:1.006 ～ 1,033)是Graves病甲亢性肝损害发生的独立危险因素(P均＜0.05).结论 Graves病甲亢性肝损害与FT3、FT4、TRAb、BMR、甲状腺重量有关.其中FT3、BMR为甲亢性肝损害发生的独立危险因素.     

甲状腺球蛋白抗体IgG亚型在桥本甲状腺炎中的分布及意义

目的 探讨血清甲状腺球蛋白抗体(TgAb)IgG亚型在桥本甲状腺炎中的分布及意义.方法 收集112例TgAb滴度升高的桥本甲状腺炎患者的血清,按甲状腺功能分为甲状腺功能减低(甲减)组、亚临床甲状腺功能减低(亚甲减)组和甲状腺功能正常组(功能正常组).采用抗原特异性ELISA方法 检测TgAb各IgG亚型阳性率及其滴度.结果 TgAb各IgG亚型阳性率分别为IgG190.2%、IgG2 58.0%、IgG3 19.6%、IgG4 87.5%.甲减组及亚甲减组IgG1亚型滴度的几何均数均高于功能正常组(分别为1:450.8,1:245.5,1:8.7,P＜0.01);甲减组与亚甲减组IgG2亚型滴度的几何均数均高于功能正常组(1:37.3,1:3.2,1:0.2,分别为P＜0.01和P＜0.05),并且甲减组IgG2亚型滴度的几何均数高于亚甲减组(P＜0.05).结论 桥本甲状腺炎TgAb亚型主要由IgG1、IgG2、IgG4组成.高滴度IgG1、IgG2可能与甲状腺功能损伤有关.     

Graves病患者血清氨基端-脑钠肽前体水平的变化

目的 研究Graves病(GD)甲亢患者血清氨基端.脑钠肽前体(NT-proBNP)的变化特点及临床意义.方法 入选GD患者269例,其中初发患者90例.测定血清甲状腺激素、促甲状腺素受体抗体(TRAb)和NT-proBNP水平.结果 血清NT-pmBNP与FT3(r=0.260,P<0.01)、FT4(r=0.297,P<0.01)和心率正相关(r=0.251,P<0.05);与超敏TSH(sTSH)负相关(r=-0.157,P<0.01).校正年龄、性别和体重指数(BMI)后,血清NT-pmBNP仍与FT3、FT4和TRAb正相关(均P<0.01).校正血清FT3,FT4、sTSH、TRAb、年龄、性别、BMI后,初发组和治疗组的血清NT-proBNP差异仍有统计学意义(P<0.01),血清FT4对NT-pwBNP有显著影响(P<0.01),NT-proBNP水平的升高在甲亢已经控制的患者中同样存在.结论 GD患者血清NT-pwBNP水平随着FT4的升高而明显上升,不受性别、年龄和BMI的影响.监测血清NT-pmBNP有助于了解GD患者的血管僵硬度和容量变化,为早期防治甲亢引起的心血管疾病提供依据.     

甲泼尼松龙冲击治疗甲状腺相关性眼病时TRAb和sICAM-1的变化及意义

目的 探讨促甲状腺素受体抗体(TRAb)、可溶性细胞间黏附分子1(sICAM-1)与甲状腺相关性眼病(TAO)病情的相关性,及其在TAO发病机制中的作用.方法 对23例TAO患者,按照临床活动性评分及眼病严重程度分级分组,给予大剂量甲泼尼龙静脉冲击治疗.分别采用放射免疫法和酶联免疫吸附法,于治疗前及每个疗程结束后第2天测定空腹外周静脉血清中TRAb和sICAM-1的浓度.结果 TRAb水平与患者病情活动性相关(P=0.020);sICAM-1水平主要与患者眼病的病程相关(P=0.015);活动性眼病组患者接受激素冲击治疗过程中TRAb的水平持续稳定下降,第3个疗程后TRAb的水平较治疗前显著下降(P＜0.05);重复测量趋势分析示活动性与非活动性眼病患者接受大剂量甲强龙冲击后TRAb和sICAM-1的水平变化趋势均不同.结论 TRAb与TAO的活动性相关,可预测并客观评价糖皮质激素的疗效;sICAM-1与患者眼病的病程相关,但是非特异性使其水平的影响因素较多,不能客观地反映激素治疗的效果.     

Serum concentrations of adiponectin and resistin in hyperthyroid Graves' disease patients

This study was undertaken to determine whether serum adiponectin and resistin levels are influenced by hyperthyroidism and autoimmune factors and to find out whether their levels are dependent on the presence of ophthalmopathy. We measured serum concentrations of adiponectin and resistin in 76 patients (63 women, 13 men) with Graves' disease (GD) and compared them with levels of the control group which consisted of 30 healthy subjects. Patients were separated into two groups according to the presence or the absence of thyroid-associated ophthalmopathy (TAO). TAO (-) group consisted of 26 subjects without eye signs of GD and TAO (+) group included 50 subjects with ophthalmopathy. The latter group was further divided into 2 subgroups: with active TAO [26 patients, clinical activity score (CAS)> or =4] and with inactive TAO (24 patients, CAS<4). Groups did not differ in age, sex, body mass index (kg/m2) and smoking habits. Compared with euthyroid subjects, hyperthyroid GD patients had elevated mean serum adiponectin concentrations (19.96+/-4.97 microg/ml vs 15.01+/-3.99 microg/ml, p<0.001). However we did not observe any disparity between the TAO (-) and TAO (+) groups (20.60+/-5.06 microg/ml vs 19.63+/-4.94 microg/ml, p=ns). Comparing patients with a CAS> or =4 and patients with a CAS<4, we found similar mean serum concentrations of adiponectin (20.04+/-5.01 microg/ml vs 18.74+/-4.83 microg/ml, p=ns). Serum levels of resistin did not differ between the hyperthyroid patients and control subjects (13.11+/-4.26 ng/ml vs 12.82+/-4.75 ng/ml, p=ns). Serum resistin levels did not differ between TAO (+) and TAO (-) groups nor in patients with active and inactive TAO. Serum adiponectin correlated significantly with free T4 (FT4), free T3 (FT3), and TSH-R antibodies (TRAb) in GD patients (r=0.40, 0.41, and 0.37, respectively; p<0.001 for each). Serum resistin levels were not correlated with thyroid hormones and thyroid antibodies. The variables that in simple linear regression analyses were found to be correlated with serum adiponectin were then used in multiple regression analysis. In a model including adiponectin as dependent variable and FT4, FT3 and TRAb levels as independent variables, FT3 and TRAb remained as parameters independently related to adiponectin level (R2=0.35, p<0.001). CONCLUSIONS: Elevated serum adiponectin levels in GD patients are related to the degree of hyperthyroidism and autoimmune process. The presence and activity of ophthalmopathy is not a modifier of serum adiponectin and resistin.     

Serum concentrations of proinflammatory cytokines in Graves' disease: effect of treatment, thyroid function, ophthalmopathy and cigarette smoking

OBJECTIVE: In the present study we have measured the concentrations of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and IL-1 receptor antagonist (IL-1Ra) in the serum of patients with Graves' disease (GD). By multivariate analysis, we have evaluated the effect of antithyroid treatment, thyroid function, the presence or absence of active thyroid-associated ophthalmopathy (TAO), the patient's smoking habits and the relation to circulating anti-thyrotropin (TSH) receptor (TRAb) and anti-thyroperoxidase antibodies (TPOAb). SUBJECTS: We studied 84 GD patients, 51 untreated and 33 receiving methimazole (MMI) therapy. Twenty-three (45%) untreated patients and 18 (54%) patients on MMI had active TAO. We also studied 67 normal subjects as controls. Thirty-one GD patients (43%) and 16 controls (36%) were smokers. RESULTS: Serum IL-6 concentrations were significantly higher in both untreated patients (P<0.001) and treated patients (P<0.006), when compared with controls. Serum sIL-6R concentrations were significantly affected by treatment (P=0.001). Serum IL-1Ra concentrations were not different in GD patients, whether treated or untreated, compared with controls. Serum IL-6 concentrations were not influenced by thyroid function and there was a significant interaction between treatment and the presence of active TAO (P=0.003). In hyperthyroid patients with active TAO serum, sIL-6R concentrations were significantly higher than in those with inactive TAO (P=0.003). In untreated GD patients there was no significant effect of thyroid function and TAO activity on the serum concentrations of TNF-alpha and IL-1 beta. Serum IL-1Ra concentrations were not affected by the presence of TAO. Smoking had no effect on serum IL-6, sIL-6R, TNF-alpha, IL-1 beta and IL-1Ra concentrations, even in the presence of an active TAO. Serum concentrations of IL-6, sIL-6R, TNF-alpha and IL-1 beta and IL-1Ra were not different in patients with and without TRAb or TPOAb, in relation to either thyroid function, TAO activity or smoking. CONCLUSIONS: Our work shows that: (i) the proinflammatory cytokine pattern in GD is greatly influenced by antithyroid drug treatment; (ii) the increased circulating IL-6/sIL-6R concentrations observed in patients with active TAO may derive from the activation of humoral reactions in sites other than the thyroid; and, (iii) cigarette smoking has no effect on serum IL-1/IL-1Ra concentrations in TAO.     

Treatment of Graves' disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study

INTRODUCTION: Hyperthyroid Graves' disease (GD) is a B-cell-mediated condition caused by TSH receptor antibodies (TRAb), which decline when GD remits. Anti-CD20 monoclonal antibody rituximab (RTX) induces transient B-cell depletion that may potentially modify the active inflammatory phase of thyroid-associated ophthalmopathy (TAO). METHODS: Nine patients with GD, (seven with active TAO, two with mild lid signs) were studied. The trial was only approved as an open pilot study; thus we compared the effect of RTX therapy to that of i.v. glucocorticoids (IVGC) in 20 consecutive patients. Patients were treated with RTX (1000 mg i.v. twice at 2-week interval) or with IVGC (500 mg i.v. for 16 weeks). TAO was assessed by the clinical activity score (CAS) and severity was classified using NOSPECS (No signs or symptoms; Only signs (lid); Soft tissue involvement; Proptosis, Extraocular muscle involvement; Corneal involvement; Sight loss). Thyroid function and lymphocyte count were measured by standardized methods. RESULTS: All patients attained peripheral B-cell depletion with the first RTX infusion. Minor side effects were reported in three patients. Thyroid function was not affected by RTX therapy and hyperthyroid patients required therapy with methimazole. After RTX, the changes in the levels of thyroglobulin antibodies, thyroperoxidase antibodies and TRAb were neither significant nor correlated with CD20+ depletion (P = NS). CAS values before RTX were 4.7 +/- 0.5 and decreased to 1.8 +/- 0.8 at the end of follow-up (P < 0.0001) and more significantly compared with IVGC (P < 0.05). Proptosis decreased significantly after RTX both in patients with active TAO (ANOVA; P < 0.0001) and those with lid signs (ANOVA; P < 0.003). The degree of inflammation (class 2) decreased significantly in response to RTX (ANOVA; P < 0.001). Relapse of active TAO was not observed in patients treated with RTX, but occurred in 10% of those treated with IVGC, who also experienced adverse effects more frequently (45 vs 33% of patients). CONCLUSIONS: RTX positively affects the clinical course of TAO, independently of either thyroid function or circulating antithyroid antibodies, including TRAb. If our findings are confirmed in large controlled studies, RTX may represent a useful therapeutic tool in patients with active TAO.     

Analysis of cellular and biochemical contents of broncho-alveolar lavage fluid from patients with pulmonary tuberculosis

To evaluate the local immune response in lung and activity of pulmonary tuberculosis. Broncho-alveolar lavage (BAL) was performed on 15 patients with pulmonary tuberculosis. Patients consisted of nine in the active stage and six in the inactive stage. Acid-fast bacilli (AFB) in BAL fluid (BALF) were found in six out of nine active stage patients (BAL-AFB positive group). The results obtained were as follows; 1) The number of total cells in BALF increased significantly in BAL-AFB positive group. BALF from two patients of this group, who were in the very early stage, revealed that the lymphocytes increased predominantly whereas neutrophils were dominant in BALF from the other four patients. 2) No case showed increase of B cells in BALF. Lymphocytes surface markers were compared between BAL-AFB positive and negative groups. No difference was found in the numbers of OKT3, OKT4 and OKT8. The positive rates of OKIal, and OKT4/8 ratio were both increased in BALF compared to the BAL-AFB positive group. 3) The numbers of OKT4 and OKT4/8 ratio in peripheral blood, which were taken simultaneously with BAL, were decreased in patients in the active stage. 4) Protein, albumin, IgG, IgA, lysozyme and alpha 1-antitrypsin levels in BALF were all increased in tuberculous patients. No correlation between the activity of tuberculosis and levels of protein, albumin, IgG and IgA was observed. Lysozyme level increased in the inactive stage of patients. On the other hand alpha 1-antitrypsin level increased in the active stage. Fibronectin level in BALF from patients was lower than that from normal controls. 5) Smoking habit had no influence on the above results. 6) Only one case showed the appearance of new lesions after BAL procedure as a complication.     

Imbalanced matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 activities in patients with thromboangiitis obliterans

The pathogenic mechanisms of thromboangiitis obliterans (TAO) are not entirely known and the imbalance of matrix metalloproteinases (MMPs) plays a role in vascular diseases. We evaluated the MMP-2 and MMP-9 circulating levels and their endogenous tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in TAO patients with clinical manifestations. The study included 20 TAO patients (n = 10 female, n = 10 male) aged 38-59 years under clinical follow-up. The patients were classified into two groups: (1) TAO former smokers (n = 11) and (2) TAO active smokers (n = 9); the control group included normal volunteer non-smokers (n = 10) and active smokers without peripheral artery disease (n = 10). Patient plasma samples were used to analyze MMP-2 and MMP-9 levels using zymography, and TIMP-1 and TIMP-2 concentrations were determined by enzyme-linked immunosorbent assays. The analysis of MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios (which were used as indices of net MMP-2 and MMP-9 activity, respectively) showed significantly higher MMP-9/TIMP-1 ratios in TAO patients (p < 0.05). We found no significant differences in MMP-2/TIMP-2 ratios (p > 0.05). We found higher MMP-9 levels and decreased levels of TIMP-1 in the TAO groups (active smokers and former smokers), especially in active smokers compared with the other groups (all p < 0.05). MMP-2 and TIMP-2 were not significantly different in patients with TAO as compared to the control group (p > 0.05). In conclusion, our results showed increased MMP-9 and reduced TIMP-1 activity in TAO patients, especially in active smokers compared with non-TAO patients. These data suggest that smoke compounds could activate MMP-9 production or inhibit TIMP-1 activity.     

系统性红斑狼疮患者外周血TB淋巴细胞Fas FasL表达及与凋亡的关系研究

目的探讨系统性红斑狼疮(SLE)患者外周血T、B淋巴细胞Fas、FasL表达及与凋亡的关系.方法采用流式细胞术(FCM)检测了30例SLE活动期患者、30例SLE非活动期患者和30名正常人外周血T、B淋巴细胞的凋亡率及Fas、FasL表达率.结果T、B淋巴细胞的Fas表达率依次为:活动期组＞非活动期组＞正常对照组(P＜0.01);FasL的表达率除B淋巴细胞在SLE活动期显著高于正常对照组外(P＜0.01),其余各组间差异无统计学意义;细胞的凋亡率在活动期显著高于非活动期(P＜0.01),而非活动期与正常对照组差异无统计学意义(P＞0.05):SLE的活动性与T或B细胞的Fas、FasL表达率间无相关关系,而与T或B细胞的凋亡率呈正相关(P＜0.01);无论是T或B细胞,Fas、FasL的表达率与凋亡率间无相关性.结论SLE患者体内外周血淋巴细胞的凋亡受到多种因素影响,但最终仍表现为凋亡率的异常增高,特别是活动期SLE,推测外周血淋巴细胞凋亡率的增高在SLE发病机制中起着重要作用.     

Graves病六种自身抗体的测定及其临床意义

本文报告157例Graves病患者六种自体抗体的测定结果,按临床表现、甲功测定及治疗情况分为未治组(甲)、治疗未控制或复发组(乙)、治疗缓解组(丙)三组。发现甲组患者TRAb、TgAb、TmAb、抗DNA抗体、ANA的阳性率分别为91.2、79.4、79.4、70.6及23.5％;抗体阳性率及结合率乙组与甲组比(除TBII P<0.05外)差异均无显著性;丙组与甲、乙两组相比其TRAb阳性率及TBII差异均有显著性(P<0.01),TmAb结合率与乙组比有显著差异(P<0.05),TgAb、TmAb、抗DNA抗体阳性率有显著差异(与甲组比P<0.01,与乙组比P<0.05);乙、丙两组IAb阳性率为5.6及4.2％。结果提示,Graves病患者血清中存有多种自体抗体,TRAb可作为检测Graves病及判断治疗效果和预后的一种可靠方法。经抗甲药物治疗后其IAb阳性率亦较高。     

Severe thyroid-associated orbitopathy in Hashimoto's thyroiditis. Report of 2 cases

Thyroid-associated orbitopathy (TAO) is characterized by immune-mediated inflammation of the extraocular muscles surrounding orbital connective tissue and adipose tissue. Severe orbitopathy related to autoimmune thyroid disease often occurs in patients with Grave's disease, but it is rare in patients with Hashimoto's thyroiditis. The pathogenesis of TAO is unclear. Several studies have noted a strong correlation between the levels of antibodies to thyrotropin receptor antibody (TRAb) and TAO in Graves' disease. Mild upper eyelid retraction has been reported to be common in Hashimoto's thyroiditis patients, however severe orbitopathy is rare. We report two cases of severe TAO in patients with Hashimoto's thyroiditis who required systemic glucocorticoid therapy and orbital irradiation to treat the TAO. The activity of the TAO was high in both patients, because their clinical activity scores (CAS) for the orbitopathy were high, and magnetic resonance imaging (MRI) showed enlargement of the extraocular muscles and an increase in T2 signal intensity and prolonged T2 relaxation time which indicate an active stage of inflammation. We tested the presence of TRAb by three different assays and were negative in both patients. Since the eye muscle damage cannot be due to TSH receptor antibodies, other pathogenetic mechanisms may be responsible for the orbitopathy in patients with Hashimoto's thyroiditis.     

Immunological aspects of Graves' disease patients in different clinical stages

Humoral immunological differences and the relation between circulating immune complexes (CIC) and the thyrotropin-receptor antibody (TRAB) were evaluated in newly diagnosed (n = 30), relapsed (n = 27) and remission patients (n = 29) with Graves' disease. CIC were assessed by C1q-binding assay (CIC-C1q) and the PEG precipitation test (CIC-PEG); TRAb by the radioreceptor method and microsomal antibody (MAb) by passive hemagglutination test. The data were expressed as mean +/- SE. No difference was observed in the CIC-C1q among newly diagnosed, relapsed and remission patients, but they were elevated vs controls (p less than 0.01, less than 0.05, less than 0.05, respectively). In newly diagnosed subjects with positive TRAb, CIC were higher than in those with negative TRAb (p less than 0.05) and also higher than in relapsed patients with positive TRAb (p less than 0.05). In newly diagnosed group CIC-C1q correlated to TRAb presence but not to TRAb values. CIC-PEG and TRAb levels were similar in newly diagnosed and relapsed patients, being higher than in controls (p less than 0.01) and in remission patients (p less than 0.01). No significant differences were observed in MAb in any of the groups. Conclusions: i) Patients in remission were immunologically active and they differed from newly diagnosed and relapsed patients by CIC-PEG and TRAb values; ii) in hyperthyroid patients with positive TRAb, CIC-C1q were higher at the initial stage of the disease; iii) A direct correlation between CIC-C1q and TRAb presence was observed in newly diagnosed patients, but no relation could be seen in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)