Abstract

The identification of panels of tumor antigens that elicit an antibody response may have utility in cancer screening, diagnosis, and establishing prognosis. Until now, autoimmunity in cancer has been mainly revealed in solid tumors. The aim of this study was to apply the proteomic approach to the identification of proteins that commonly elicit a humoral response in acute leukemia (AL). Sera from 21 newly diagnosed patients with AL, 20 patients with solid tumors, and 22 noncancer controls were analyzed for antibody-based reactivity against AL proteins resolved by two-dimensional electrophoresis. As a result, autoantibody against a protein identified by mass spectrometry as Rho GDP dissociation inhibitor 2 was detected in sera from 15 of 21 patients with AL (71%). By contrast, such antibody was detected in sera from one of 20 patients with solid tumors (5%) and one of 22 noncancer controls (4.5%). Five other protein autoantibodies were also found in AL patients with a high frequency and constituted the major target antigens of the AL autoimmune response. The findings of autoantibodies against Rho GDP dissociation inhibitor 2 and other proteins in sera of patients with AL suggest that the proteomic approach we have implemented may have utility for the development of a serum-based assay for AL screening and diagnosis.

Highlights

  • The identification of panels of tumor antigens that elicit an antibody response may have utility in cancer screening, diagnosis, and establishing prognosis

  • There is some evidence that chronic lymphocytic leukemia (CLL)1 B-lymphocytes are frequently committed to production of natural autoantibodies, and the occurrence of autoantibodies in CLL is of prognostic relevance (14 –16)

  • We report in this study that sera from 71% of the acute leukemia (AL) patients exhibited IgG-based reactivity against proteins identified as GDP dissociation inhibitor (GDI)

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Summary

Introduction

The identification of panels of tumor antigens that elicit an antibody response may have utility in cancer screening, diagnosis, and establishing prognosis. Autoantibody against a protein identified by mass spectrometry as Rho GDP dissociation inhibitor 2 was detected in sera from 15 of 21 patients with AL (71%) By contrast, such antibody was detected in sera from one of 20 patients with solid tumors (5%) and one of 22 noncancer controls (4.5%). There is substantial evidence for a humoral immune response to cancer in humans as demonstrated by the identification of antibodies against a number of intracellular and surface antigens in patients with various tumor types [1,2,3]. Proteomics-based Identification of Leukemia Antigens immune response to acute leukemia (AL) in humans and whether the autoantibodies are specific to AL, we implemented a proteomic approach to identify proteins that induce an antibody response in patients with AL. Five other protein autoantibodies were found in AL patients with a significantly higher frequency and constituted the major target antigens of the AL autoimmune response

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