格雷夫斯病和桥本甲状腺炎中的血清CD40/CD40L系统与可溶性Fas、FasL及自身免疫反应的体液标志物相关。
Serum CD40/CD40L system in Graves' disease and Hashimoto's thyroiditis related to soluble Fas, FasL and humoral markers of autoimmune response.
作者信息
Mysliwiec Janusz, Oklota Magdalena, Nikolajuk Agnieszka, Waligorski Dariusz, Gorska Maria
机构信息
Department of Endocrinology, Diabetology and Internal Diseases, Medical University of Bialystok, Poland.
出版信息
Immunol Invest. 2007;36(3):247-57. doi: 10.1080/08820130601069715.
Activated CD4 T cells' express CD40 ligand (CD154) interacting with CD40 on the B cells surface, protecting them from Fas-mediated apoptosis and in this study, influence humoral response. The aim of the study was to assess soluble CD40 and CD154 in Graves' disease (GD) and Hashimoto's thyroiditis (HT) in relation to Fas and FasL and to the markers of humoral response: aTPO, aTG and aTSHR. The study was carried out in 5 groups of subjects: 1/14 patients with GD in euthyreosis on methimazol (euGD), 2/20 patients with hyperthyroid GD (hrGD), 3/15 patients with HT in euthyreosis on levothyroxine (euHT), 4/16 patients with hypothyroid Ht (hoHT), 5/12 healthy volunteers, age and sex-matched to groups 1-4. The serum levels of CD40, CD154, Fas and FasL, aTPO and aTG were determined by ELISA and aTSHR was determined by the RIA method. CD40 serum concentration was significantly higher in hoHT individuals: 55.8 (24.0-83.2) pg/ml (p<0.01) and euHT patients: 51.2 (20.0-80.1) (p<0.05) as compared to the controls. Also sCD40L values were significantly increased in euHT individuals: 5.1 (1.0-11.8) (p<0.05) and hoHT patients: 3.9 (0.7-11.2) ng/ml (p<0.05) as compared to the controls. There was a positive correlation between sCD40 and sCD154 in the patients studied (r=0.36, p<0.001). In HT patients we found positive correlations between sCD40 and aTPO (r=0.45, p<0.001) and sFas (r=0.36, p<0.05) as well as a negative correlation between sCD40 and FasL (r=-0.24, p<0.05). In GD patients there was a positive correlation between sCD40 and aTSHR (r=0.28, p<0.05). In summary, our results suggest that CD40/CD154 interaction plays an important role in the regulation of autoimmune humoral response, both in Hashimoto's thyroiditis and Graves' disease. Fas-mediated apoptosis seems to be involved in this process especially in Hashimoto thyroiditis. Soluble CD40 may serve as a marker of the active stage of autoimmune thyroid disease.
活化的CD4 T细胞表达与B细胞表面的CD40相互作用的CD40配体（CD154），保护B细胞免受Fas介导的凋亡，并且在本研究中，影响体液免疫反应。本研究的目的是评估Graves病（GD）和桥本甲状腺炎（HT）中可溶性CD40和CD154与Fas、FasL以及体液免疫反应标志物：抗甲状腺过氧化物酶抗体（aTPO）、抗甲状腺球蛋白抗体（aTG）和促甲状腺素受体抗体（aTSHR）的关系。该研究在5组受试者中进行：1/14例服用甲巯咪唑处于甲状腺功能正常状态的GD患者（甲状腺功能正常的GD，euGD），2/20例甲状腺功能亢进的GD患者（甲亢性GD，hrGD），3/15例服用左甲状腺素处于甲状腺功能正常状态的HT患者（甲状腺功能正常的HT，euHT），4/16例甲状腺功能减退的HT患者（甲减性HT，hoHT），5/12名年龄和性别与1 - 4组匹配的健康志愿者。通过酶联免疫吸附测定（ELISA）法测定血清中CD40、CD154、Fas和FasL、aTPO和aTG的水平，通过放射免疫分析（RIA）法测定aTSHR。与对照组相比，hoHT患者的CD40血清浓度显著更高：55.8（24.0 - 83.2）pg/ml（p<0.01），euHT患者的CD40血清浓度也显著更高：51.2（20.0 - 80.1）（p<0.05）。与对照组相比，euHT患者的可溶性CD40配体（sCD40L）值也显著升高：5.1（1.0 - 11.8）（p<0.05），hoHT患者的sCD40L值为3.9（0.7 - 11.2）ng/ml（p<0.05）。在所研究的患者中，sCD40与sCD154之间存在正相关（r = 0.36，p<0.001）。在HT患者中，我们发现sCD40与aTPO（r = 0.45，p<0.001）和sFas（r = 0.36，p<0.05）之间存在正相关，以及sCD40与FasL之间存在负相关（r = -0.24，p<0.05）。在GD患者中，sCD40与aTSHR之间存在正相关（r = 0.28，p<0.05）。总之，我们的结果表明，CD40/CD154相互作用在桥本甲状腺炎和Graves病的自身免疫体液免疫反应调节中起重要作用。Fas介导的凋亡似乎参与了这一过程，尤其是在桥本甲状腺炎中。可溶性CD40可能作为自身免疫性甲状腺疾病活动期的标志物。
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