From basic research to clinical practice

Abstract

The understanding of type 1 diabetes (T1DM) has undergone a profound transformation over the past decades. Traditionally regarded as a disease beginning with the onset of clinical hyperglycemia, T1DM is now recognized as a dynamic autoimmune process that starts years before clinical manifestation and progresses through well-defined stages. This new paradigm has established autoantibodies against pancreatic β-cell antigens as essential biomarkers for early detection, risk stratification, disease classification, and the identification of individuals who may benefit from interventions aimed at preserving β-cell function. Translating this biological knowledge into clinical practice has required the development of reliable, sensitive, and standardized immunodiagnostic tools.

For nearly three decades, our research group has contributed to this translational process through the development of an integrated platform based on the expression and characterization of recombinant human autoantigens and their application in different immunoanalytical technologies. From the initial studies using recombinant GAD65 to the incorporation of proinsulin, IA-2, and ZnT8, the optimization of both prokaryotic and eukaryotic expression systems enabled the production of antigens with appropriate immunochemical properties for application in radiobinding assays (RBA), enzyme-linked immunosorbent assays (ELISA), surface plasmon resonance (SPR), flow cytometric microsphere-based immunoassays (FloCMIA), and platforms employing chimeric recombinant molecules.

These developments have not only expanded the diagnostic capabilities for autoimmune diabetes but have also enabled a more comprehensive characterization of the autoimmune response, improved the differential diagnosis of adult autoimmune diabetes, facilitated the implementation of screening strategies, and provided innovative tools adapted to emerging clinical scenarios. Today, the availability of disease-modifying therapies and the implementation of prediction and staging programs demand robust, accessible, cost-effective, and clinically validated immunoanalytical methods.

The experience of our laboratory illustrates how basic research in molecular biology, protein engineering, and immunochemistry can be translated into technological innovations with direct clinical impact. In the new era of T1DM, autoantibodies are no longer viewed solely as diagnostic markers but as critical tools for identifying individuals at risk of progression to clinical T1DM, selecting candidates for disease-modifying therapies, and advancing toward a preventive and precision medicine approach. This trajectory exemplifies the essence of translational research: transforming discoveries generated at the laboratory bench into tangible clinical benefits for individuals at risk of, or living with, autoimmune diabetes.