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 Blood, 1 January 2008, Vol. 111, No. 1, pp. 302-308.
Prepublished online as a Blood First Edition Paper on September 18, 2007; DOI 10.1182/blood-2007-05-090654.

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NEOPLASIA

Accurate identification of paraprotein antigen targets by epitope reconstruction

Seshi R. Sompuram1,2, Gerassimos Bastas2, Kodela Vani1, and Steven A. Bogen1,2

1 Medical Discovery Partners, Boston, MA; and 2 Department of Pathology and Laboratory Medicine, Boston University School of Medicine, MA

We describe the first successful clinical application of a new discovery technology, epitope-mediated antigen prediction (E-MAP), to the investigation of multiple myeloma. Until now, there has been no reliable, systematic method to identify the cognate antigens of paraproteins. E-MAP is a variation of previous efforts to reconstruct the epitopes of paraproteins, with the significant difference that it provides enough epitope sequence data so as to enable successful protein database searches. We first reconstruct the paraprotein's epitope by analyzing the peptides that strongly bind. Then, we compile the data and interrogate the nonredundant protein database, searching for a close match. As a clinical proof-of-concept, we apply this technology to uncovering the protein targets of para-proteins in multiple myeloma (MM). E-MAP analysis of 2 MM paraproteins identified human cytomegalovirus (HCMV) as a target in both. E-MAP sequence analysis determined that one para-protein binds to the AD-2S1 epitope of HCMV glycoprotein B. The other binds to the amino terminus of the HCMV UL-48 gene product. We confirmed these predictions using immunoassays and immunoblot analyses. E-MAP represents a new investigative tool for analyzing the role of chronic antigenic stimulation in B-lymphoproliferative disorders.


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This article has been cited by other articles:


Home page
 Mol. Cell. ProteomicsHome page
G. Bastas, S. R. Sompuram, B. Pierce, K. Vani, and S. A. Bogen
Bioinformatic Requirements for Protein Database Searching Using Predicted Epitopes from Disease-associated Antibodies
Mol. Cell. Proteomics, February 1, 2008; 7(2): 247 - 256.
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