Abstract
The increased incidence of autoantibodies in malignancies has been described since the 1970s. Thus the ability to determine molecular fingerprinting of autoantibodies (antibody signatures) may provide useful clinical diagnostic and prognostic information. This review describes the use of several proteomics approaches for the identification of antigens recognized by these autoantibodies. Serological proteome analysis combines separation of tumor cell proteins on two-dimensional gel electrophoresis gels, Western blotting with sera of patients and healthy subjects, and identification of the detected antigens by MS. Alternatively multiple affinity protein profiling combines isolation of the antigens recognized by patient antibodies by two-dimensional immunoaffinity chromatography and identification by MS/MS. The use and limitations of reverse phase protein microarrays for testing patient serum containing autoantibodies are also considered. Lastly the most important difficulty of any proteomically identified autoantibody signature is validation in patient cohorts or clinical samples.
Highlights
The increased incidence of autoantibodies in malignancies has been described since the 1970s
The observation that patients’ sera sometimes recognize tumor-associated antigens raises the possibility that detection of this humoral immune response could provide both diagnostic and prognostic information
The ability to determine a molecular fingerprinting of autoantibodies or of complementary antigens would be relevant for serological screening tests for malignancies
Summary
The increased incidence of autoantibodies in malignancies has been described since the 1970s. The serological identification of human tumor antigens that could be at the origin of patients’ autoantibodies was pursued as soon as the 1970s by Old and co-workers [14, 15] For this purpose, they developed an approach called autologous typing. Using autologous serum and cultured cell lines from cancer patients and extensive absorption analyses, a few antigens were detected and further defined with the techniques available in those days Molecular characterization of these antigens was generally beyond reach primarily because the antibodies were not of high titer, and their clinical value remained subject to debate. The observation that patients’ sera sometimes recognize tumor-associated antigens raises the possibility that detection of this humoral immune response could provide both diagnostic and prognostic information. This ability can be termed “cancer immunomics” (12, 16 –18)
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