Advancing Autoantibody Detection: A Journey from Conventional to State-of-the-Art Methods

Autoimmune diseases are a diverse group of disorders characterized by immune disturbances that cause aberrant B cell and T cell reactivity to normal constituents of the host1. Autoantibodies are commonly found in individuals with autoimmune diseases. A large number of autoantibodies are directed against intracellular or extracellular targets such as nucleic acids, structural proteins, enzymes, RNA binding proteins, receptors, cytokines, among others2. The detection of these autoantibodies is key to the diagnosis and classification of patients with autoimmune diseases. In addition, some studies have shown that autoantibodies can appear years before the onset of an autoimmune disease; therefore, the detection of these antibodies would serve as early predictors of risk and would also help to choose a possible therapeutic intervention to prevent or delay the disease progression3. Several methods, such as enzyme-linked immunosorbent assay (ELISA), immunofluorescence, fixed tissue or cell-based assays, are commonly used for the detection of autoantibodies. Although these technologies are limited in sensitivity, specificity, and sample throughput, therefore, new experimental techniques are continuously developed to discover novel autoantigens involved in autoimmune diseases4. There are several limitations in the detection of autoantibodies, such as sensitivity and specificity, temporal variability in autoantibody levels, technical limitations, subjective interpretation, and lack of standards and quality controls in the tests. Autoantibody tests are only a diagnostic tool and must be used in combination with clinical evaluation for an accurate diagnosis. In this chapter, we will describe the technologies used in the detection of classic and new autoantibodies, exploring the assessment of clinical relevance, accuracy, validation, and possible regulatory requirements as an approved diagnostic test that could be promoted in routine clinical practice.