Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado 80045, USA.
Curr Opin Endocrinol Diabetes Obes. 2011 Aug;18(4):235-40. doi: 10.1097/MED.0b013e32834803ae.
To update on the clinical trials using antigen-specific therapies in autoimmune diabetes.
Type 1 diabetes is now a predictable disease with the measurement of islet autoantibodies, and the incidence is increasing dramatically. Well tolerated and effective interventions are needed to stop the underlying autoimmune destruction of insulin-producing beta cells. Beta-cell antigens, insulin and glutamic acid decarboxylase, are being used to preserve endogenous insulin production in individuals with new-onset diabetes and to prevent diabetes. The results of antigen-specific immune intervention trials are reviewed and consideration is given to future directions for inducing tolerance in type 1 diabetes.
Antigen-specific immune therapies act by enhancing regulatory T cell function, in animal models often locally and selectively in islets or pancreatic lymph nodes while inhibiting effector T cells. This therapeutic pathway provides a safe treatment to preserve beta cell function in new-onset diabetic individuals with the GAD-Alum vaccine being the most extensively studied therapy. Insulin is being used in many forms to prevent diabetes and stop the underlying autoimmune process. For the future, combination immune therapies targeting different pathways in the immune system will be needed to effectively induce sustained tolerance in type 1 diabetes.
更新自身免疫性糖尿病中使用抗原特异性治疗的临床试验。
通过胰岛自身抗体的检测,1 型糖尿病现在是一种可预测的疾病,其发病率正在急剧上升。需要耐受良好且有效的干预措施来阻止胰岛素产生β细胞的潜在自身免疫破坏。β细胞抗原、胰岛素和谷氨酸脱羧酶被用于在新诊断的糖尿病患者中保留内源性胰岛素的产生,并预防糖尿病。本文综述了抗原特异性免疫干预试验的结果,并考虑了在 1 型糖尿病中诱导耐受的未来方向。
抗原特异性免疫疗法通过增强调节性 T 细胞的功能起作用,在动物模型中通常在胰岛或胰腺淋巴结局部和选择性地起作用,同时抑制效应 T 细胞。这种治疗途径为新诊断的糖尿病个体提供了一种安全的治疗方法,以保留β细胞功能,其中 GAD-Alum 疫苗是研究最多的治疗方法。胰岛素以多种形式用于预防糖尿病和阻止潜在的自身免疫过程。未来,需要针对免疫系统中不同途径的联合免疫疗法,以有效地在 1 型糖尿病中诱导持续的耐受。