From rheumatic diseases to cancer - role of autoantibodies as diagnostic biomarkers

In rheumatic diseases no individual autoantibody-antigen system has sufficient combination of sensitivity and specificity to serve as a useful diagnostic biomarker. Instead, several antigen-antibody systems constructed as profiles of biomarkers are highly effective in distinguishing one disorder from another. In lupus, anti-double strand DNA and anti-Sm distinguishes it from scleroderma, where the profile is anti-DNA topoisomerase 1 and anti-centromere proteins. The autoantigens are cell components involved in universal and basic gene expression pathways, such as Sm in precursor mRNA splicing and DNA topoisomerase 1 in DNA replication and transcription [1].Autoantibodies in cancer target intracellular molecules referred to as TAAs (tumor-associated antigens). As in rheumatic disorders, no individual autoantibody-antigen system has sensitivity and specificity to serve as a stand-alone diagnostic marker [2]. Most tumors show multiple antibody specificities and with panels of TAA-anti-TAAs (analogous toprofiles) the cumulative sensitivity and specificity reaches diagnostic significance. Different tumorigenesis pathways are activated in similar cell-type tumors from the same organ and are the driving mechanisms behind the autoantibody response. The immune responses are directed to products of oncogenes and tumor-suppressor genes such as p53 and other proteins that regulate and modulate the functions of p53 [3-5].Protein phosphatase 2A (PP2A) is an important tumor suppressor protein. It is a serine/threonine phosphatase and is a trimeric complex. The B subunit is recruited from several intracellular proteins and the type of B subunit determines the substrate of its tumor suppressor activity. One of the B subunits, p90, was identified in our laboratory with autoantibody from a patient with hepatocellular carcinoma [6]. It was found to co-immunoprecipitate with other subunits of PP2A [7] and was shown to function as an inhibitor of the tumor-suppressor activity of PP2A.The