title: Evaluation of a specific diagnostic marker for rheumatoid arthritis based on cyclic citrullinated peptide.
abstract: A specific peptide marker for diagnosing rheumatoid arthritis (RA) was found based on cyclic citrullinated peptide (CCP) using the following three steps: (1) analysis of the binding epitope of autoimmune antibodies using ϵ-aminocaproic acid-modified peptides; (2) RA diagnosis using sequence-modified peptides; and (3) evaluation of the peptides' diagnostic performance for RA diagnosis. Ninety-five serum samples were analyzed by ELISA and compared using MedCalc (version 15.2.1). Microplate binding ϵ-aminocaproic acid was added to the N- or C-terminal of the CCP sequence. The N-terminal anchoring peptide assay showed 15% higher specificity compared with the C-terminal anchoring peptide assay. Based on this result, the hydrophilic C-terminal sequence of CCP was substituted with a hydrophobic amino acid. Among the sequence-modified peptides, CCP11A (in which alanine was substituted for the 11th amino acid of CCP) assay showed the highest sensitivity (87%) and specificity (100%) for RA diagnosis. Thus, CCP11A was selected as a possible specific marker peptide for RA diagnosis and further analyzed. The results of this analysis indicated that CCP11A showed better specificity than the CCP assay in both healthy individuals (11% better) and OA cohort (20% better). From these results, CCP11A was evaluated as a specific marker for diagnosing RA with higher diagnostic performance.
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Park
authors.affiliation: Department of Material Science and Engineering, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Pyun
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea; Department of Biological Chemistry, Korea University of Science and Technology, Daejon 305-350, Republic of Korea.
authors.forename: Hafeza
authors.initials: H
authors.lastname: Akter
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea; Department of Biological Chemistry, Korea University of Science and Technology, Daejon 305-350, Republic of Korea.
authors.forename: Binh Thanh
authors.initials: BT
authors.lastname: Nguyen
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea; Department of Biological Chemistry, Korea University of Science and Technology, Daejon 305-350, Republic of Korea. Electronic address: mjkang1@kist.re.kr.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015119:Aminocaproic Acid / Q000737:chemistry; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001666:Binding Sites, Antibody; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D015119:Aminocaproic Acid
keywords: CCP; Diagnostic marker; Osteoarthritis; Rheumatoid arthritis; Sequence modification; ϵ-aminocaproic acid