Development and deployment of antigen arrays for investigation of B-cell fine specificity in autoimmune disease

Abstract

Recent developments in proteomic technologies have enabled the high-throughput, multiplex measurement of large panels of antibodies in biological fluids of patients with immune-driven diseases. Antigen microarrays are increasingly being used to delineate the natural history of autoantibody formation and epitope spread, and thus gain insight into the pathogenesis of autoimmune diseases, as well as into host immunity and its shortcomings. Characterization of autoimmunity that precedes the onset of clinically apparent disease has the potential to guide disease prevention using either conventional immunosupression or novel, antigen-specific tolerizing therapies. In addition, autoantibody profiling has the potential to identify molecular subtypes of a disease, which could allow for prediction of disease outcomes such as severity, tissue damage, and response to therapy.

Figure 1

Schematic representation of planar and bead-based microarrays. A. Planar antigen microarrays, B. Bead-based peptide antigen array, C. Bead-based protein antigen array. In all cases, antigen is bound to the experimental surface, probed with antibody-containing fluid sample, washed, incubated with secondary detection antibody, and visualized for quantitation of primary antibody reactivity.