- Oral presentation
- Open Access
From rheumatic diseases to cancer - role of autoantibodies as diagnostic biomarkers
Arthritis Research & Therapy volume 14, Article number: O2 (2012)
Rheumatology has pioneered in the study of autoantibodies by showing that they are not only involved in pathogenesis but are also highly useful as diagnostic biomarkers. The diagnostic biomarker aspect of autoimmunity has gained increasing importance in cancer and many of the insights gained in Rheumatology have contributed to understanding the significance of autoantibodies in cancer.
Features of autoantibodies in rheumatic disorders
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 .
Features of autoantibodies in cancer
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 . 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 . It was found to co-immunoprecipitate with other subunits of PP2A  and was shown to function as an inhibitor of the tumor-suppressor activity of PP2A.
The immune system is capable of sensing dysregulation of tumorigenesis pathways. The goal of continuing research is in developing TAA-anti-TAAs for detecting cancer in individual patients and profiles which are common to specific types of tumors.
Tan EM: Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol. 1989, 44: 93-151.
Tan EM, Zhang J: Autoantibodies to tumor-associated antigens: reporters from the immune system. Immunol Rev. 2008, 222: 328-340. 10.1111/j.1600-065X.2008.00611.x.
Robles AI, Harris CC: Clinical outcomes and correlates of TP53 mutations and cancer. Cold Spring Harb Perspect Biol. 2010, 2 (3): a001016-10.1101/cshperspect.a001016. Review
Levine AJ, Oren M: The first 30 years of p53: growing ever more complex. Nat Rev Cancer. 2009, 9: 749-758. 10.1038/nrc2723.
Efeyan A, Serrano M: p53: guardian of the genome and policeman of the oncogenes. Cell Cycle. 2007, 6: 1006-1010. 10.4161/cc.6.9.4211.
SooHoo L, Chan EK: Cloning and characterization of a novel 90 kDa 'companion' autoantigen of p62 overexpressed in cancer. Oncogene. 2002, 21: 5006-5015. 10.1038/sj.onc.1205625.
Juntilla MR, Puustinen P, Niemela M, et al: CIP2A inhibits PP2A in human malignancies. Cell. 2007, 130: 51-62. 10.1016/j.cell.2007.04.044.