Islet Autoantibodies and Type 1 Diabetes: Does the Evidence Support Screening?

[摘要] Type 1 diabetes (T1D)3 is a chronic progressive autoimmune disorder with complex polygenic susceptibility, usually associated with certain HLA alleles (IDDM1 locus). Environmental factors, which are poorly defined, also contribute to the pathogenesis. T1D is characterized by lymphocyte infiltration into the islets of Langerhans in the pancreas, leading to inflammation and selective destruction of the insulin-producing β-cells, resulting in hyperglycemia (1). Patients with T1D fail to produce insulin and are dependent on exogenous insulin to maintain life. Although it is considerably less common than type 2 diabetes, the worldwide prevalence of T1D is increasing by approximately 3% per annum. The incidence varies widely among countries. In Americans under the age of 20 years, the prevalence of T1D rose by 23% between 2001 and 2009, and >30 000 people are diagnosed annually in the US with T1D. Progression to T1D is typically marked by the presence of islet-specific autoantibodies in the serum. In humans, autoantibodies are present months to years before disease onset, and a similar trend is seen in the nonobese diabetic (NOD) mouse model of autoimmune diabetes (2). The rate of T1D development varies among individuals, possibly due to non-HLA genetic factors and/or environmental factors beyond the initial trigger.Most of the current information on the pathogenesis of T1D from the initial triggers to the final effector stages of β-cell destruction has been derived from animal models that mimic the human disease (3). T lymphocytes are central determinants for β-cell destruction in T1D. Nevertheless, autoantibodies and B lymphocytes are components of some autoimmune diseases and may contribute to the pathogenesis of T1D. Multiple studies have documented the role of autoantibodies and B lymphocytes in NOD mice. Observations include a low incidence of diabetes in NOD mice that are genetically deficient in B lymphocytes and the prevention of diabetes …

[学科分类] 过敏症与临床免疫学