自身免疫性甲状腺疾病甲状腺组织中凋亡调控蛋白Fas/FasL、Bcl-2/Bax的表达及意义

目的探讨凋亡调控蛋白Fas/FasL、Bcl-2/Bax在Graves病(GD)和桥本氏病(HT)中的表达及意义。方法取外科手术切取的GD及HT病人甲状腺组织标本,颈部手术时取正常甲状腺组织作为对照;采用免疫组织化学方法检测甲状腺标本Fas/FasL、Bcl-2/Bax的表达和分布状况。结果(1)Fas/FasL在GD和HT甲状腺滤泡上皮细胞表达均较正常对照组增高(P<0.01)。(2)在GD甲状腺滤泡上皮细胞Bcl-2及Bax表达明显高于HT组及正常对照组,以Bcl-2表达强度显著高于同组Bax(P<0.01),而在HT,Bcl-2表达强度与正常对照组比较差异无统计学意义。(3)GD与HT相比较,GD甲状腺滤泡细胞及浸润淋巴细胞Fas,Bcl-2抗原表达均强于HT,但其浸润淋巴细胞表达强度明显低于同组甲状腺滤泡细胞(均P<0.05)。结论Fas/FasL高表达和Bcl-2的低表达可能引起HT甲状腺滤泡上皮细胞的凋亡。在GD,Fas、Bax诱导细胞凋亡的作用可能被高表达Bcl-2对抗,从而致甲状腺体积增大、功能亢进。此外,Bcl-2与Bax表达强度的比值对于凋亡的调控有重要影响作用。     

自身免疫性甲状腺疾病甲状腺组织中bcl-2家族蛋白的表达

目的研究凋亡相关基因bcl鄄2家族蛋白bcl鄄2、mcl鄄1、bcl鄄XL和bax在自身免疫性甲状腺疾病(AITD)甲状腺组织中的表达特征及与AITD发病机制之间的内在联系。方法以甲状腺腺瘤旁正常甲状腺组织为对照(C组,20例),采用免疫组织化学ElivisionTM二步染色法检测凋亡相关蛋白bcl鄄2、mcl鄄1、bcl鄄XL和bax在桥本甲状腺炎(HT组,33例)和Graves病(GD组,28例)患者甲状腺组织中的表达与分布。结果bcl鄄2蛋白表达强度GD组>C组>HT组(P<0.01);mcl鄄1蛋白表达强度GD组>C组>HT组(P<0.01);bcl鄄XL蛋白表达强度HT组和GD组强于C组(P<0.01),但HT组和GD组间差异无统计学意义(P>0.05);bax蛋白的表达强度HT组>GD组和C组(P<0.01),但GD组和C组间差异无统计学意义(P>0.05);HT组中,在淋巴细胞浸润区域附近的甲状腺滤泡上皮细胞(TEC)bcl鄄2表达弱,bax和mcl鄄1表达强;远离淋巴细胞浸润区域的TECbcl鄄2表达强,bax和mcl鄄1表达弱(P<0.05)。结论(1)抗凋亡bcl鄄2和mcl鄄1蛋白在HT中表达的减弱以及在GD中表达的增强对于HT甲状腺滤泡细胞凋亡的增加和GD甲状腺滤泡细胞的增殖可能起一定作用;(2)bax蛋白在HT中表达增强所起的促凋亡的作用对疾病的发生发展起一定作用;(3)bcl鄄2与bax表达强度的比值对于凋亡的调控起重要作用;(4)bcl鄄2家族蛋白bc     

甲状腺过氧化物酶抗体球蛋白抗体微粒体抗体在甲状腺自身免疫性疾病中的改变

目的 观察甲状腺过氧化物酶抗体(TPO Ab)、甲状腺球蛋白抗体(TG Ab)和甲状腺微粒体抗体(TM Ab)在自身免疫性甲状腺疾病(AITD)中的改变,探讨TPO Ab在临床诊断和治疗上的作用和意义.方法 收集AITD患者,根据甲状腺功能不同分为甲状腺功能亢进(简称甲亢)组(Graves病、GD,57例)、甲低组(桥本氏甲状腺炎、HT,48例)、亚甲低组(41例)和AITD复诊组(甲状腺功能恢复正常1～6个月,41例).另取一级亲属无GD或HT的健康人群53例为对照组.采用放射免疫分析法检测血清中甲状腺自身抗体(TPO Ab、TG Ab和TM Ab)及甲状腺激素和促甲状腺激素(FT3、FT4,sTSH)水平.结果 甲亢组、甲低组和亚甲低组中TPO Ab阳性率(87.70%、97.20%、100.00%)均明显高于同组内TG Ab阳性率(43.90%、60.42%、48.78%)和TM Ab阳性率(43.90%、79.10%、60.98%);3种甲状腺自身抗体的阳性率和阳性患者的抗体水平均高于相应的对照组.AITD复诊组的TPO Ab阳性患者的抗体水平[(683.04±606.55)kU/L]明显低于甲亢组、甲低组和亚甲低组[(1049.31±941.00)、(106 440.79±272.38)、(5133.01±4449.67)kU/L].结论 TPO Ab在AITD的诊断更具有代表意义,抗体水平为AITD治疗及预后评估提供了重要的依据.     

自身免疫性甲状腺疾病患者甲状腺内Th1/Th2细胞失衡研究

目的　探讨甲状腺中Th1/Th2 细胞失衡在自身免疫性甲状腺疾病 (AITD)发病中的作用。方法　选取 13例Graves病 (GD)患者、12例桥本甲状腺炎 (HT)患者 ,并以 8例非毒性结节性甲状腺肿患者作为对照进行研究。采用免疫组化染色方法检测这些患者甲状腺内单个核细胞 (ITMC)的γ 干扰素(IFN γ)和白介素 4(IL 4)细胞因子抗原表达 (分别代表Th1,Th2 分泌的细胞因子 ) ,并与外周血甲状腺刺激性抗体 (TSAb)、甲状腺球蛋白抗体 (TGAb)、甲状腺微粒体抗体 (TMAb)等免疫学指标进行相关分析。结果　 ( 1)GD、HT患者ITMC的IL 4、IFN γ阳性表达明显高于对照组 (均P <0 .0 1) ;GD患者ITMC的IL 4阳性表达明显高于IFN γ阳性表达 ;而HT患者ITMC的IFN γ阳性表达则明显高于IL 4阳性表达(均P <0 .0 5 ) ;( 2 )GD患者ITMC的IL 4阳性表达与TSAb显著正相关 (r =0 .67,P <0 .0 1) ,ITMC的IFN γ阳性表达与TSAb无相关性 ;HT患者ITMC的IFN γ阳性表达与TGAb、TMAb均呈显著正相关(分别为r =0 .65 ,r =0 .5 9,均P <0 .0 5 ) ,但ITMC的IL 4阳性表达与TGAb、TMAb均无相关性。结论　GD患者Th1/Th2 细胞平衡失衡偏向以Th2 占优势的免疫应答 ,而HT患者Th1/Th2 平衡失衡偏向以Th1占优势的免疫应答。     

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.     

自身免疫甲状腺病单个核细胞体外培养产生抗甲状腺球蛋白抗体

利用ELISA技术检测自身免疫甲状腺病(AITD)患者周围血单个核细胞(PBMC)体外培养产生甲状腺球蛋白抗体(TGA)。结果表明:体外培养AITD患者PBMC能够产生可测出的TGA,阳性率31.25％。桥本甲状腺炎(HT)较Graves甲亢(GD)更易体外产生TGA,阳性率分别为44.19％和16.22％。美洲商陆刺激体外产生TGA增加,而可溶性甲状腺球蛋白对体外产生TGA无刺激作用。抗甲状腺药物他巴唑能够抑制体外产生TGA。HT患者血清TGA水平与体外产生TGA呈正相关,但未观察到GD患者血清TGA与体外产生TGA的相关性。提示AITD患者体内存在可引起自身抗体产生的免疫调节紊乱、HT与GD在产生自身抗体的机制上可能有所不同。     

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。     

CD54、CD80、HLA-DR在Graves病和桥本甲状腺炎甲状腺滤泡上皮中的表达

目的观察正常人、Graves病（GD）、桥本甲状腺炎（HT）、甲状腺组织CD54、CD80、HLA—DR的表达。方法免疫组化SP法测定上述各组甲状腺组织CD54、CD80、HLA—DR的表达水平。结果正常甲状腺组织甲状腺滤泡上皮细胞（TEC）几乎不表达CD54和HLA—DR，而GD组和HT组有较高水平的CD54和HLA-DR表达，以HT表达水平最高，3组间比较差异有统计学意义（均P〈0．01）；HT患者甲状腺CD80表达高于GD组和正常人，差异有统计学意义（均P〈0．01），GD组甲状腺CD80表达很低，与正常人相比差异没有统计学意义。结论CD54和HLA-DR在GD和HT的发病机制中起重要作用，CD80在HT的发病中起重要作用。     

调节性T细胞和TGF-β1在自身免疫性甲状腺疾病中的作用

目的观察初发自身免疫性甲状腺疾病(AITD)患者外周血中CD4+CD25+调节性T细胞(Treg)数量和功能变化及转化生长因子β1(TGF-β1)水平,探讨其在AITD发病机制中的作用。方法收集初发Graves病(GD)组30例、初发桥本甲状腺炎(HT)组20例、健康对照组20例,用流式细胞仪分析各组外周血CD4+T细胞及CD4+CD25+Treg占CD4+的百分比,RT-PCR法检测各组外周血PBMC中FOXP3 mRNA表达量,ELISA法检测血清TGF-β1含量。结果初发GD、初发HT患者外周血CD4+CD25+Treg占CD4+T细胞的比率、FOXP3 mRNA表达水平均明显低于对照组(P均<0.05),初发GD、初发HT患者外周血清中TGF-β1水平较对照组均显著升高(P均<0.05)。结论 CD4+CD25+Treg、FOXP3及TGF-β1可能参与了AITD的发生、发展过程,Treg数量减少或FOXP3表达不足可反馈性引起血清TGF-β1水平升高。     

自身免疫性甲状腺病的病因

过去,对自身免疫性甲状腺病(AITD)病因的研究多集中于有单一病因解释的Graves病(GD)、桥本氏甲状腺炎(HT)及原发性甲状腺衰竭。随     

Nontoxic nodular goiter and papillary thyroid carcinoma are not associated with peripheral blood lymphocyte sensitization to thyroid cells

We tested the claim that uni- and multinodular goiter (UNG and MNG) and papillary carcinoma (PC) of the thyroid are autoimmune thyroid diseases (AITD) similar to Graves' disease (GD) and Hashimoto's thyroiditis (HT). The expression of HLA-DR on cultured thyroid epithelial cells (thyrocytes) from UNG, MNG, and PC after coculture with autologous peripheral blood mononuclear cells (PBMC) was compared with that on GD and HT cells. The thyrocytes also were cultured with interferon-gamma (IFN gamma) alone. A cytotoxicity assay involving 51Cr-labeled thyrocytes, anti-HLA-DR, and complement was used to determine HLA-DR expression. Stimulation of thyrocytes with 200 U/mL IFN gamma induced HLA-DR (expressed as a cytotoxicity index) equally well on all thyrocytes [AITD (n = 6): IFN gamma, 23.8 +/- 7.7 (+/- SD); unstimulated, 3.6 +/- 2.0; UNG (n = 6), MNG (n = 9), and PC (n = 5): IFN gamma, 22.5 +/- 4.7; unstimulated, 4.0 +/- 3.0]. When cocultured with autologous PBMC, the values were: AITD, 24.9 +/- 10.1; UNG, MNG, and PC, 3.8 +/- 3.7 (P less than 0.001). The supernatants from the AITD cocultures had higher IFN gamma concentrations (by RIA) than those from the other cocultures. We conclude that in UNG, MNG, and PC, the peripheral blood helper T-lymphocytes are not sensitized to thyrocyte membrane antigen(s); consequently, little if any IFN gamma is produced in cocultures, and hence, there is no increase in thyrocyte HLA-DR expression, unlike the situation in AITD (GD and HT). Thus, UNG, MNG, and PC are not primarily autoimmune in nature, as defined by a lack of sensitization of the PBMC of such patients to thyroid antigen(s).     

Anti-Saccaromyces Cerevisiae antibodies (ASCA) are elevated in autoimmune thyroid disease ASCA in autoimmune thyroid disease

Environmental factors have been implicated in the development of autoimmune thyroid disease (AITD). Anti-Saccaromyces Cerevisiae Antibodies (ASCA) were shown to be elevated in several autoimmune diseases. The aim of the study was to determine ASCA levels and their relationship with thyroid autoantibodies in patients with AITD. One-hundred and twelve patients with AITD (age 41.1±12.8 years; F/M:96/16) and 103 healthy controls (38.5±10.3 years; F/M:82/21) were included. Twenty-four patients had Graves disease (GD), and 88 had Hashimoto's thyroiditis (HT). ASCA IgA and IgG, TSH, free T4, anti-thyroglobulin, and anti-thyroid peroxidase antibody concentrations were determined. ASCA IgA positivity in patients with GD (16.6%) was similar to patients with HT (13.6%) and was higher than controls (5.8%). No significant difference was present between the frequencies of IgG positivity among GD (12.5%), HT (7.9%), and control groups (5.8%). The mean levels of ASCA IgA and IgG were comparable within the groups. No correlation of ASCA and anti-thyroglobulin and anti-thyroid peroxidase levels was observed. Increased IgA ASCA positivity is observed in patients with GD, suggesting a role of environmental stimuli in its pathogenesis. The role of ASCA in the etiology of AITD needs to be further examined.     

Association between thyroid stimulating hormone receptor gene intron polymorphisms and autoimmune thyroid disease in a Chinese Han population

Autoimmune thyroid disease (AITD) is a multifactorial disease with a genetic susceptibility and environmental factors. The thyroid stimulating hormone receptor gene (TSHR) which is expressed on the surface of the thyroid epithelial cell is thought to be the main auto-antigen and a significant candidate for genetic susceptibility to AITD. This case-control study aimed at evaluating the association between single nucleotide polymorphisms (SNP) of TSHR and AITD in a Chinese Han population. We recruited 404 patients with Graves' disease (GD), 230 patients with Hashimoto's thyroiditis (HT) and 242 healthy controls. The Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometer (MALDI-TOF-MS) Platform was used to detect five SNPs (rs179247, rs12101255, rs2268475, rs1990595, and rs3783938) in TSHR gene. The frequencies of allele T and TT genotype of rs12101255 in GD patients were significantly increased compared with those of the controls (P=0.004/0.015, OR=1.408/1.446). The allele A frequency of rs3783938 was greater in HT patients than in the controls (P=0.025, OR=1.427). The AT haplotype (rs179247-rs12101255) was associated with an increased risk of GD (P=0.010, OR=1.368). The allele A of rs179247 was associated with ophthalmopathy in GD patients. These data suggest that the polymorphisms of rs12101255 and rs3783938 are associated with GD and HT, respectively.     

Relationship between autoimmune thyroid disease and nephropathy: A clinicopathological study

The association of nephropathy with autoimmune thyroid disease (AITD) has been reported previously. However, there is limited information on the relationship between thyroid autoantibodies and nephropathy. A retrospective study was conducted using the medical records of 246 patients with nephropathy, 82 of whom had concurrent AITD. General characteristics, thyroid function, autoantibodies, and the pathological types of nephropathy were analyzed. Immunohistochemistry was used to detect the thyroglobulin antibody (TG-Ab) and thyroid peroxidase antibody (TPO-Ab) in the kidneys. We found nephropathy patients with AITD exhibited higher serum levels of TPO-Ab, TG-Ab, thyroid-stimulating hormone receptor antibody (TR-Ab), and immunoglobulin G (IgG) (P < .05). Compared with the nephropathy without AITD group, the nephropathy with AITD group exhibited higher proportions of membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS), and relatively lower proportions of mesangial proliferative glomerulonephritis (MsPGN) and minimal change nephropathy (MCN) (P = .005). TPO-Ab and TG-Ab levels in the kidney were more prevalent in nephropathy patients with AITD than those without AITD (P = .015 and P = .026, respectively). Subgroup analysis demonstrated that serum levels of thyroid stimulating hormone (TSH), TG-Ab, TPO-Ab, immunoglobulin M (IgM), and IgG in the MN group were significantly higher, whereas the levels of free thyroxine (FT4) and estimated glomerular filtration rate (eGFR) were lower, as compared with MN with Hashimoto thyroiditis (HT) group (P < .05). TPO-Ab and TG-Ab expression levels in the kidneys were more prevalent in the MN group than in the MN with HT group (P = .034). The expression levels of FT4, TG-Ab, TPO-Ab, and thyroid-stimulating hormone receptor antibody (TSHR-Ab) in the serum were significantly higher in the MN group than in the MN with Graves disease (GD) group (P < .05). The expression of TPO-Ab in the kidneys was more prevalent in the MN group than in the MN with GD group (P = .011). In sum, the expressions of TPO-Ab and TG-Ab were more prevalent in the kidneys of patients with nephropathy and AITD. Our findings indicate that TPO-Ab and TG-Ab may play a role in the development of AITD-related nephropathy.     

自身免疫性甲状腺疾病患者血清瘦素水平观察

目的 观察自身免疫性甲状腺疾病(AITD)中Graves病(GD)和桥本氏甲状腺炎(HT)患者血清瘦素水平,探讨瘦素在AITD发病机制中的免疫学作用.方法 102例体质量指数(BMI)和年龄等因素相匹配的女性AITD初诊患者,根据临床表现及实验室检查结果分为3组:GD甲亢组,HT甲低组,亚甲低组,另设性别、年龄、BMI匹配的对照组.免疫化学发光法检测血清FT3、FT4、sTSH,ELISA法检测血清瘦素水平.结果 GD甲亢组血清FT3、FT4水平[(19.74±15.39)、(78.25±58.68)pmol/L]明显高于对照组[(4.87±0.25)、(15.96±3.15)pmol/L],而sTSH[(0.15±0.08)mU/L]和瘦素水平[(8.73±1.92)μg/L]明显低于对照组[(3.81±0.19)mU/L、(12.38±3.51)μg/L].组间比较差异均有统计学意义(P＜0.01或＜0.05).而HT甲低组兀FT3、FT4水平[(3.36±0.26)、(6.95±3.29)pmol/L]均明显低于对照组(P＜0.05),而sTSH[45.48±35.83)mU/L]和瘦素水平[(17.17±3.82)μg/L]明显高于对照组(P＜0.01或＜0.05).亚甲低组FT3、FT4水平[(4.67±0.60)、(14.87±2.14)pmol/L]与对照组比较差异无统计学意义(P＞0.05),而sTSH[(13.67土8.66)mU/L]和瘦素水平[(16.25±3.67)μg/L]均明显高于对照组(P＜0.01或＜0.05).结论 瘦素在AITD发病机制中可能具有一定的免疫调节作用,而AITD患者瘦素水平也可能受sTSH影响.     

Association of circulating antibodies against double-stranded and single-stranded DNA with thyroid autoantibodies in Graves' disease and Hashimoto's thyroiditis patients.

The occurrence of antinuclear antibody (ANA), rheumatoid factor (RF), antibodies to double-stranded DNA (anti-dsDNA) and to single-stranded DNA (anti-ssDNA) was investigated in 51 patients with autoimmune thyroid diseases (AITD), and in 25 matched control subjects. In comparison with controls, the prevalence of anti-dsDNA was 74.5% in AITD patients (p=0.0001), 82.0% in 39 hyperthyroid Graves' disease (GD) (p=0.0001), and 50.0% in 12 euthyroid Hashimoto's thyroiditis (HT) patients (p=0.0001). The prevalence of anti-ssDNA was 90.1% in AITD (94.8% in GD and 75% in HT; p=0.001). The concentration of both anti-dsDNA and anti-ssDNA were higher (p=0.002) in AITD, in GD (p=0.001), and in HT (p=0.01) patients than in controls. Two patients with AITD were identified as positive for ANA. RF was detected in 4 AITD patients. Positive correlation was noted between anti-dsDNA with T4 (p=0.001), T3 (p=0.002), thyroid peroxidase antibody (anti-TPO) (p=0.0001), and TSH (p=0.001) values but not with thyroglobulin antibody (anti-Tg). Serum anti-ssDNA values were also correlated with T3 (p=0.0001), TSH (p=0.003), and anti-TPO (p=0.0001). However, by using a multiple regression analysis only anti-TPO remained associated with anti-dsDNA and both anti-Tg and anti-TPO with anti-ssDNA values. The predisposition to develop systemic autoimmune disorders is not influenced by thyroid hormones. The elevated prevalence of serum anti-dsDNA and anti-ssDNA in AITD patients points out that we must be aware of the risk for predisposition for the development of other systemic autoimmune diseases.     

Searching for the autoimmune thyroid disease susceptibility genes: from gene mapping to gene function

The autoimmune thyroid diseases (AITD) are complex diseases that are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility, in combination with external factors (e.g., dietary iodine), is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been used to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked with AITD, and in some of these loci putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD) and Hashimoto's thyroiditis (HT), and some are common to both diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g., human leukocyte antigen, cytotoxic T lymphocyte antigen-4) and thyroid-specific genes (e.g., TSH receptor, thyroglobulin). Most likely these loci interact, and their interactions may influence disease phenotype and severity. It is hoped that in the near future additional AITD susceptibility genes will be identified and the mechanisms by which they induce AITD will be unraveled.     

Relation of CD30 molecules on T-cell subsets to the severity of autoimmune thyroid disease.

The prognosis of patients with autoimmune thyroid disease (AITD) varies. To clarify the immunologic differences among patients with various severities of AITD, we examined two types of molecules on peripheral T lymphocytes: CD195 (CCR5), which express dominantly on CD4(+) type 1 helper T (T(H)1) cells, and CD30, which is known as a marker of CD4(+) type 2 helper T (T(H)2) cells and a regulatory molecule of CD8(+) autoreactive cytotoxic T cells. We found presence of patients with high proportion (> 9%) of CD30 expression in CD4(+) cells in a group of patients with Graves' disease (GD) in remission compared to the patients with intractable GD and a decrease in the intensity of CD30 expression on CD8(+) cells from patients with severe Hashimoto's disease (HD) treated for hypothyroidism compared to patients with untreated and euthyroid HD. There was no difference in CD195 expression between these patients with GD or HD with different severities, but there was a decreased intensity of CD195(+) cells in thyrotoxic patients with GD. These results indicate that CD30 molecules on CD4(+) and CD8(+) cells may be related to the severities of GD and HD, respectively.     

促甲状腺激素受体,甲状腺过氧化物酶及甲状腺球蛋白基因表达…

为探讨促甲状腺激素受体。甲状腺过氧化物酶及甲状腺球蛋白ｍＲＮＡ在自身免疫甲状腺疾病（ＡＩＴＤ）病人甲状腺组织的表达情况及其相互关系，应用Ｎｏｒｔｈｅｒｎ印记杂交技术观察了ＴＳＨ受体、ＴＰＯ以及ＴＧ ｍＲＮＡ在７例Ｇｒａｖｅｓ病（ＧＤ），２例桥本甲状腺素炎（ＨＴ）病人甲状腺组织中的表达。研究显示：ＴＳＨ受体ｍＲＮＡ与ＴＰＯ和ＴＧ ｍＲＮＡ在ＧＤ组和ＨＴ组表达不一致，ＧＤ组ＴＳＨ受体ｍＲＮＡ与ＴＰＯ和