Sera from Patients with IDDM and Healthy Individuals have Antibodies to ICA69 on Western Blots but do not Immunoprecipitate Liquid Phase Antigen

Only Multiple Autoantibodies to Islet Cells (ICA), Insulin, GAD65, IA-2 and IA-2β Predict Immune-Mediated (Type 1) Diabetes in Relatives

“…Peripherin antibodies described in NOD mice [39] has not to our knowledge yet been reported in diabetic humans. ICA-69 is another candidate [40], however antibodies to the recombinant protein were found to be equally common in patients and controls while sera from patients with type 1 diabetes could not immunoprecipitate the antigen from normal islets [41]. Identification of the additional ICA antigen(s) are thus of considerable contemporary interest, since autoimmune responses to it do not appear to be pathogenic; this may have implications for future antigen-based immunotherapies.…”

Cellular and Humoral Immunity against Cow's Milk Proteins in Type 1 Diabetes

“…Molecular mimicry has been proposed after the identification of sequence similarities between BSA and ICA69 [15,47], a protein also present in -cells and once thought to be a diabetesassociated autoantigen [48]; between -casein and carboxypeptidase H and GLUT 2 [26], which have also been postulated as autoantigens [49][50][51]; and between -lactoglobulin and retinol binding protein, which is expressed in -cells [52]. However, none of these human proteins was confirmed to be a major autoantigen in type 1 diabetes [53,54], the specificity of these sequence similarities is unclear, and moreover a concomitant response to the cow's milk protein and corresponding islet protein has never been demonstrated. Furthermore, the varied cow's milk protein targets reported in ours and other cohorts argue against a specific mimicry mechanism.…”

Autoantibodies in Diabetes

“…It seems likely that, as a consequence of islet damage and antigen release in an inflamed islet, there is increased immune reactivity to a wide range of pancreatic islet components. Some of these immune responses are detected at low frequency in the diabetic population, their target antigens may be widely expressed in tissues, and antibodies may be detected in autoimmune diseases other than diabetes [109,110]. There is currently little evidence that detection of autoantibodies to antigens other than insulin, GAD, and IA-2 adds significantly to diabetes prediction.…”