Bahn R S, Heufelder A E
Department of Internal Medicine, Mayo Clinic/Foundation, Rochester, MN 55905.
Autoimmunity. 1992;13(1):75-9. doi: 10.3109/08916939209014638.
Histologic similarities exist between the tissues involved in the extrathyroidal manifestations of Graves' disease, namely ophthalmopathy and pretibial dermopathy. Both conditions are characterized by an accumulation of glycosaminoglycans (GAGs) and an infiltration of lymphocytes. We have shown that interleukin-1 and transforming growth factor-beta, cytokines released by the local inflammatory cell infiltrate, are capable of stimulating GAG synthesis by retroocular and pretibial fibroblasts. Additionally, affected retroocular and pretibial fibroblasts demonstrate an enhanced induction of HLA-DR in response to interferon-gamma treatment and both cell types express the 72 kDa heat shock protein in vivo and in vitro. Retroocular and pretibial fibroblasts from patients with Graves' ophthalmopathy and pretibial dermopathy thus seem to possess unique immunological features that may render them more susceptible to the autoimmune process in Graves' disease. Chronic stimulation of fibroblasts by cytokines released in the local inflammatory milieu may result in excessive GAG production. The accumulation of these hydrophilic mucopolysaccharides, with its associated edema, leads to the clinical manifestations of Graves' ophthalmopathy and pretibial dermopathy.
格雷夫斯病的甲状腺外表现所涉及的组织，即眼病和胫前皮肤病变，在组织学上存在相似之处。这两种病症的特征都是糖胺聚糖（GAGs）的积聚和淋巴细胞浸润。我们已经表明，局部炎症细胞浸润释放的细胞因子白细胞介素-1和转化生长因子-β能够刺激眼后和胫前成纤维细胞合成GAG。此外，受影响的眼后和胫前成纤维细胞在接受干扰素-γ治疗后，HLA-DR的诱导增强，并且这两种细胞类型在体内和体外均表达72 kDa热休克蛋白。因此，格雷夫斯眼病和胫前皮肤病变患者的眼后和胫前成纤维细胞似乎具有独特的免疫学特征，这可能使它们更容易受到格雷夫斯病自身免疫过程的影响。局部炎症环境中释放的细胞因子对成纤维细胞的慢性刺激可能导致GAG产生过多。这些亲水性粘多糖的积聚及其相关的水肿导致了格雷夫斯眼病和胫前皮肤病变的临床表现。
