Yokota I, Shima K
Department of Pediatrics, Tokushima University School of Medicine.
Rinsho Byori. 1998 Apr;46(4):331-7.
Glutamic acid decarboxylase (GAD) catalyzes the formation of gamma-aminobutyric acid (GABA), which is a major transmitter in the central nervous system. Two forms of GAD (GAD65 and GAD67) are known to be expressed in human tissues and GAD65 is predominantly expressed in pancreatic beta-cells. Recent findings revealed that GAD functions as an autoantigen in human autoimmunity, especially in insulin-dependent diabetes mellitus (IDDM). GAD is a key antigen for the development of autoimmunity against beta-cells and the production of GADAb precedes other autoantibodies such as IAA and ICA512/IA-2Ab prior to the clinical onset of IDDM. At onset, GADAb is detected in 50-80% of patients using RIA or RBA method. Factors that influence the positivities and titers of GADAb at onset, such as onset age, sex, presence of autoimmunity against thyroid, HLA type, have been reported. After onset, GADAb titer decreased more slowly than that of ICA512/IA-2Ab. These findings suggest that autoantibodies against beta-cells, such as GADAb, may develop independently. The presence of GADAb in relatives of IDDM patients and NIDDM patients predicts the development of beta-cell destruction in combination with other anti-islet autoantibodies.
谷氨酸脱羧酶(GAD)催化γ-氨基丁酸(GABA)的形成,γ-氨基丁酸是中枢神经系统中的一种主要神经递质。已知两种形式的GAD(GAD65和GAD67)在人体组织中表达,且GAD65主要在胰腺β细胞中表达。最近的研究发现表明,GAD在人类自身免疫中起自身抗原的作用,尤其是在胰岛素依赖型糖尿病(IDDM)中。GAD是针对β细胞自身免疫发展的关键抗原,在IDDM临床发病前,GAD抗体(GADAb)的产生先于其他自身抗体,如胰岛素自身抗体(IAA)和胰岛细胞抗原512/胰岛抗原2抗体(ICA512/IA - 2Ab)。发病时,使用放射免疫分析(RIA)或放射配体结合分析(RBA)方法,在50 - 80%的患者中可检测到GADAb。已报道了一些影响发病时GADAb阳性率和滴度的因素,如发病年龄、性别、甲状腺自身免疫的存在、人类白细胞抗原(HLA)类型等。发病后,GADAb滴度下降比ICA512/IA - 2Ab更慢。这些发现表明,针对β细胞的自身抗体,如GADAb,可能独立产生。IDDM患者和非胰岛素依赖型糖尿病(NIDDM)患者亲属中GADAb的存在,与其他抗胰岛自身抗体一起可预测β细胞破坏的发生。