Elevated blood Hsp60, its structural similarities and cross-reactivity with thyroid molecules, and its presence on the plasma membrane of oncocytes point to the chaperonin as an immunopathogenic factor in Hashimoto's thyroiditis
Elevated blood Hsp60, its structural similarities and cross-reactivity with thyroid molecules, and its presence on the plasma membrane of oncocytes point to the chaperonin as an immunopathogenic factor in Hashimoto's thyroiditis
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DOI：
10.1007/s12192-013-0460-9
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发表时间：
2014-05-01
影响因子：
3.8
通讯作者：
Cappello, Francesco
中科院分区：
文献类型：
--
作者：
Gammazza, Antonella Marino;Rizzo, Manfredi;Cappello, Francesco
热休克蛋白60可能在各种炎症和自身免疫性疾病中发挥的作用正在研究中，但关于桥本甲状腺炎（HT）的信息很少。为了填补这一空白，在目前的工作中，我们将注意力集中在Hsp 60参与HT发病机制。我们发现，与对照组相比，HT患者血液中的Hsp 60水平升高。伴侣蛋白免疫定位在甲状腺组织标本HT患者，无论是在甲状腺细胞和癌细胞（Hurthle细胞）与对照组（甲状腺肿）相比，具有较高的水平。在肿瘤细胞中，我们发现Hsp 60不仅在细胞质中，而且在质膜上，如双免疫荧光细针穿刺细胞学所示。通过生物信息学分析，我们发现Hsp 60分子中与甲状腺球蛋白（TG）和甲状腺过氧化物酶（TPO）分子具有显著的结构相似性，这支持了抗TG和TPO的自身抗体可能识别癌细胞质膜上的Hsp 60的观点。这也得到了ELISA获得的数据的支持，显示抗TG和抗TPO抗体与人重组Hsp 60交叉反应。细胞表面的抗体-抗原（Hsp 60）反应可以很好地介导甲状腺细胞的损伤和破坏，使炎症持续存在。重组Hsp 60的实验没有显示HT患者外周血单个核细胞产生细胞因子的刺激。总之，这些结果使我们假设Hsp 60可能是通过抗体介导的免疫机制在HT发病机制中的积极参与者。
The role Hsp60 might play in various inflammatory and autoimmune diseases is under investigation, but little information exists pertaining to Hashimoto's thyroiditis (HT). With the aim to fill this gap, in the present work, we directed our attention to Hsp60 participation in HT pathogenesis. We found Hsp60 levels increased in the blood of HT patients compared to controls. The chaperonin was immunolocalized in thyroid tissue specimens from patients with HT, both in thyrocytes and oncocytes (Hurthle cells) with higher levels compared to controls (goiter). In oncocytes, we found Hsp60 not only in the cytoplasm but also on the plasma membrane, as shown by double immunofluorescence performed on fine needle aspiration cytology. By bioinformatics, we found regions in the Hsp60 molecule with remarkable structural similarity with the thyroglobulin (TG) and thyroid peroxidase (TPO) molecules, which supports the notion that autoantibodies against TG and TPO are likely to recognize Hsp60 on the plasma membrane of oncocytes. This was also supported by data obtained by ELISA, showing that anti-TG and anti-TPO antibodies cross-react with human recombinant Hsp60. Antibody-antigen (Hsp60) reaction on the cell surface could very well mediate thyroid cell damage and destruction, perpetuating inflammation. Experiments with recombinant Hsp60 did not show stimulation of cytokine production by peripheral blood mononuclear cells from HT patients. All together, these results led us to hypothesize that Hsp60 may be an active player in HT pathogenesis via an antibody-mediated immune mechanism.