A contra capture protein array platform for studying post-translationally modified (PTM) auto-antigenomes

Kailash Karthikeyan, Kristi Barker, Yanyang Tang, Peter Kahn, Peter Wiktor, Al Brunner, Vinicius Knabben, Bharath Takulapalli, Jane Buckner, Gerald Nepom, Joshua LaBaer, Ji Qiu

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2324-2337
Number of pages14
JournalMolecular and Cellular Proteomics
Volume15
Issue number7
DOIs
StatePublished - Jul 1 2016

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Protein Array Analysis
Rheumatoid Arthritis
Antibodies
Antigens
Autoantigens
Proteins
Antibody Formation
Flap Endonucleases
Insulin-Like Growth Factor Binding Protein 6
Osteopontin
Insulin-Like Growth Factor I
Autoimmune Diseases
Epitopes
Assays
Peptides

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Analytical Chemistry

Cite this

A contra capture protein array platform for studying post-translationally modified (PTM) auto-antigenomes. / Karthikeyan, Kailash; Barker, Kristi; Tang, Yanyang; Kahn, Peter; Wiktor, Peter; Brunner, Al; Knabben, Vinicius; Takulapalli, Bharath; Buckner, Jane; Nepom, Gerald; LaBaer, Joshua; Qiu, Ji.

In: Molecular and Cellular Proteomics, Vol. 15, No. 7, 01.07.2016, p. 2324-2337.

Research output: Contribution to journalArticle

Karthikeyan, K, Barker, K, Tang, Y, Kahn, P, Wiktor, P, Brunner, A, Knabben, V, Takulapalli, B, Buckner, J, Nepom, G, LaBaer, J & Qiu, J 2016, 'A contra capture protein array platform for studying post-translationally modified (PTM) auto-antigenomes', Molecular and Cellular Proteomics, vol. 15, no. 7, pp. 2324-2337. https://doi.org/10.1074/mcp.M115.057661
Karthikeyan, Kailash ; Barker, Kristi ; Tang, Yanyang ; Kahn, Peter ; Wiktor, Peter ; Brunner, Al ; Knabben, Vinicius ; Takulapalli, Bharath ; Buckner, Jane ; Nepom, Gerald ; LaBaer, Joshua ; Qiu, Ji. / A contra capture protein array platform for studying post-translationally modified (PTM) auto-antigenomes. In: Molecular and Cellular Proteomics. 2016 ; Vol. 15, No. 7. pp. 2324-2337.
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