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Mol Cell Proteomics. 2016 Jul;15(7):2324-37. doi: 10.1074/mcp.M115.057661. Epub 2016 May 2.

A Contra Capture Protein Array Platform for Studying Post-translationally Modified (PTM) Auto-antigenomes.

Author information

1
From the ‡Biodesign Institute, Center for Personalized Diagnostics, Arizona State University, Tempe, Arizona 85287;
2
§Engineering Arts LLC, Phoenix, Arizona 85076;
3
From the ‡Biodesign Institute, Center for Personalized Diagnostics, Arizona State University, Tempe, Arizona 85287; §Engineering Arts LLC, Phoenix, Arizona 85076;
4
¶Benaroya Research Institute, Seattle, Washington 98101.
5
From the ‡Biodesign Institute, Center for Personalized Diagnostics, Arizona State University, Tempe, Arizona 85287; Ji.Qiu@asu.edu.

Abstract

Aberrant modifications of proteins occur during disease development and elicit disease-specific antibody responses. We have developed a protein array platform that enables the modification of many proteins in parallel and assesses their immunogenicity without the need to express, purify, and modify proteins individually. We used anticitrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) as a model modification and profiled antibody responses to ∼190 citrullinated proteins in 20 RA patients. We observed unique antibody reactivity patterns in both clinical anticyclic citrullinated peptide assay positive (CCP+) and CCP- RA patients. At individual antigen levels, we detected antibodies against known citrullinated autoantigens and discovered and validated five novel antibodies against specific citrullinated antigens (osteopontin (SPP1), flap endonuclease (FEN1), insulin like growth factor binding protein 6 (IGFBP6), insulin like growth factor I (IGF1) and stanniocalcin-2 (STC2)) in RA patients. We also demonstrated the utility of our innovative array platform in the identification of immune-dominant epitope(s) for citrullinated antigens. We believe our platform will promote the study of post-translationally modified antigens at a breadth that has not been achieved before, by both identifying novel autoantigens and investigating their roles in disease development. The developed platforms can potentially be used to study many autoimmune disease-relevant modifications and their immunogenicity.

PMID:
27141097
PMCID:
PMC4937507
DOI:
10.1074/mcp.M115.057661
[Indexed for MEDLINE]
Free PMC Article

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