Evidence that nasal insulin induces immune tolerance to insulin in adults with autoimmune diabetes.

Objective: Insulin in pancreatic β-cells is a target of autoimmunity in type 1 diabetes. In the NOD mouse model of type 1 diabetes, oral or nasal administration of insulin induces immune tolerance to insulin and protects against autoimmune diabetes. Evidence for tolerance to mucosally administered insulin or other autoantigens is poorly documented in humans.

Measurement of islet cell antibodies in the Type 1 Diabetes Genetics Consortium: efforts to harmonize procedures among the laboratories.

Background: and

Purpose: Three network laboratories measured antibodies to islet autoantigens. Antibodies to glutamic acid decarboxylase (GAD65 [GADA]) and the intracellular portion of protein tyrosine phosphatase (IA-2(ic) [IA-2A]) were measured by similar, but not identical, methods in samples from participants in the Type 1 Diabetes Genetics Consortium (T1DGC).

Methods: All laboratories used radiobinding assays to detect antibodies to in vitro transcribed and translated antigen, but with different local standards, calibrated against the World Health Organization (WHO) reference reagent.

Autoimmunity to both proinsulin and IGRP is required for diabetes in nonobese diabetic 8.3 TCR transgenic mice.

T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) induce diabetes in nonobese diabetic (NOD) mice. TCR transgenic mice with CD8(+) T cells specific for IGRP(206-214) (NOD8.3 mice) develop accelerated diabetes that requires CD4(+) T cell help.

Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP.

Type 1 diabetes (T1D) is characterized by immune responses against several autoantigens expressed in pancreatic beta cells. T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) can induce T1D in NOD mice. However, whether immune responses to multiple autoantigens are caused by spreading from one to another or whether they develop independently of each other is unknown.

Development of autoantibodies to islet antigens during childhood: implications for preclinical type 1 diabetes screening.

Objective: Serum islet antibodies signify increased risk for type 1 diabetes (T1D). Knowledge of the relationship between age and seroconversion would guide screening for at-risk individuals. We aimed to determine the effectiveness of islet antibody screening in early childhood, in particular the proportion of negative children who subsequently seroconverted.