Green L M, LaBue M, Lazarus J P, Colburn K K
JL Pettis, Veterans Medical Center, Department of Research-151, Loma Linda, CA 92357, USA.
Lupus. 1995 Jun;4(3):187-96. doi: 10.1177/096120339500400305.
MRL-lpr/lpr mice are genetically predisposed to develop a systemic lupus erythematosus-like syndrome that is clinically very similar to the human disease. The results presented here demonstrate, for the first time to our knowledge, that MRL-lpr/lpr mice also develop thyroiditis as part of their systemic autoimmune disorder. The thyroid gland was infiltrated by immunocomponent cells with defined lymphoid follicular centers and extensive interstitial lymphocytes dispersed throughout the thyroid epithelium. All the diseased mice were hypothyroid with reduced, relative levels of thyroid hormone (free T4) and elevated levels of thyroid-stimulating hormone (TSH). They also had high concentrations of circulating IgG class autoantibodies directed against thyroglobulin, thyroperoxidase and double-stranded DNA. The MRL-+/+ age-matched allelic counterpart mice had relatively few lymphocytes in their thyroid tissue, and normal levels of thyroxine and TSH. The non-diseased mice also had undetectable levels of thyroid reactive autoantibodies tested for by enzyme-linked immunosorbent assays. Collectively these findings document that the MRL-lpr/lpr mice spontaneously develop autoimmune thyroiditis and can be used as a model for the study of thyroid-specific autoimmunity.
MRL-lpr/lpr小鼠具有遗传易感性,易患一种系统性红斑狼疮样综合征,在临床上与人类疾病非常相似。据我们所知,此处呈现的结果首次证明,MRL-lpr/lpr小鼠还会发生甲状腺炎,作为其系统性自身免疫性疾病的一部分。甲状腺被免疫细胞浸润,有明确的淋巴滤泡中心,大量间质淋巴细胞分散在整个甲状腺上皮中。所有患病小鼠均为甲状腺功能减退,甲状腺激素(游离T4)相对水平降低,促甲状腺激素(TSH)水平升高。它们还具有高浓度的循环IgG类自身抗体,这些抗体针对甲状腺球蛋白、甲状腺过氧化物酶和双链DNA。年龄匹配的MRL-+/+等位基因对照小鼠甲状腺组织中的淋巴细胞相对较少,甲状腺素和TSH水平正常。通过酶联免疫吸附测定检测,未患病小鼠的甲状腺反应性自身抗体水平也无法检测到。这些发现共同证明,MRL-lpr/lpr小鼠自发发生自身免疫性甲状腺炎,可作为研究甲状腺特异性自身免疫的模型。