Department of Biochemistry, Nara Medical University, Kashihara, Japan; Department of General Medicine, Nara Medical University, Kashihara, Japan.
Clin Exp Immunol. 2013 Oct;174(1):1-9. doi: 10.1111/cei.12142.
The regenerating gene (Reg) was isolated originally as a gene specifically over-expressed in regenerating pancreatic islets and constitute a growth factor family. Reg gene product (Reg) is important in the pathophysiology of various human inflammatory diseases. Recently, the possible involvement of human REG in the regeneration of salivary ductal epithelial cells of patients with primary Sjögren's syndrome (SS) was reported. However, the expression of the REG family genes in minor salivary glands (MSG) and the occurrence of anti-REG Iα autoantibodies in SS patients were obscured. In this study, we examined the expression of REG family genes in the MSG of SS and screened anti-REG Iα autoantibodies in SS. The mRNA levels of REG family genes in MSG were quantified using real-time reverse transcription-polymerase chain reaction (RT-PCR) and REG Iα expression in the MSG was analysed by immunohistochemistry. The mRNA level of REG Iα in the MSG of SS patients was significantly higher than that of control. REG Iα protein was expressed highly in SS ductal epithelial cells. Anti-REG Iα autoantibodies in the sera were found in 11% of SS. All the MSG in the anti-REG Iα autoantibody-positive group showed REG Iα expression, whereas only 40% showed REG Iα expression in the anti-REG Iα autoantibody-negative group. The anti-REG Iα autoantibody-positive group showed significantly lower saliva secretion and a higher ratio of grade 4 (by Rubin-Holt) in sialography. These data suggest strongly that autoimmunity to REG Iα might play a role in the degeneration of MSG ductal epithelial cells in primary SS.
再生基因（Reg）最初被分离出来，作为在再生胰岛中特异性过表达的基因，并构成生长因子家族。Reg 基因产物（Reg）在各种人类炎症性疾病的病理生理学中具有重要意义。最近，有报道称人类 REG 可能参与原发性干燥综合征（SS）患者唾液腺导管上皮细胞的再生。然而，REG 家族基因在小唾液腺（MSG）中的表达以及 SS 患者抗 REG Iα 自身抗体的发生情况尚不清楚。在这项研究中，我们检测了 SS 患者 MSG 中 REG 家族基因的表达，并筛选了 SS 患者的抗 REG Iα 自身抗体。使用实时逆转录聚合酶链反应（RT-PCR）定量测定 MSG 中 REG 家族基因的 mRNA 水平，并通过免疫组织化学分析 MSG 中 REG Iα 的表达。SS 患者 MSG 中 REG Iα 的 mRNA 水平明显高于对照组。REG Iα 蛋白在 SS 导管上皮细胞中高表达。在 11%的 SS 患者血清中发现了抗 REG Iα 自身抗体。抗 REG Iα 自身抗体阳性组的所有 MSG 均显示 REG Iα 表达，而抗 REG Iα 自身抗体阴性组中只有 40%显示 REG Iα 表达。抗 REG Iα 自身抗体阳性组的唾液分泌明显减少，唾液腺造影显示 4 级（Rubin-Holt 分级）的比例更高。这些数据强烈表明，REG Iα 的自身免疫可能在原发性 SS 中 MSG 导管上皮细胞的退化中起作用。
