Technology Innovation for Discovering Renal Autoantibodies in Autoimmune Conditions

Autoimmune glomerulonephritis is a homogeneous area of renal pathology with clinical relevance in terms of its numerical impact and difficulties in its treatment. Systemic lupus erythematosus/lupus nephritis and membranous nephropathy are the two most frequent autoimmune conditions with clinical relevance. They are characterized by glomerular deposition of circulating autoantibodies that recognize glomerular antigens. Technologies for studying renal tissue and circulating antibodies have evolved over the years and have culminated with the direct analysis of antigen-antibody complexes in renal bioptic fragments. Initial studies utilized renal microdissection to obtain glomerular tissue. Obtaining immunoprecipitates after partial proteolysis of renal tissue is a recent evolution that eliminates the need for tissue microdissection. New technologies based on 'super-resolution microscopy' have added the possibility of a direct analysis of the interaction between circulating autoantibodies and their target antigens in glomeruli. Peptide and protein arrays represent the new frontier for identifying new autoantibodies in circulation. Peptide arrays consist of 7.5 million aligned peptides with 16 amino acids each, which cover the whole human proteome; protein arrays utilize, instead, a chip containing structured proteins, with 26.000 overall. An example of the application of the peptide array is the discovery in membranous nephropathy of many new circulating autoantibodies including formin-like-1, a protein of podosomes that is implicated in macrophage movements. Studies that utilize protein arrays are now in progress and will soon be published. The contribution of new technologies is expected to be relevant for extending our knowledge of the mechanisms involved in the pathogenesis of several autoimmune conditions. They may also add significant tools in clinical settings and modify the therapeutic handling of conditions that are not considered to be autoimmune.