TY - JOUR
T1 - The use of synthetic peptides for detection of anti-citrullinated protein antibodies in rheumatoid arthritis
AU - Trier, Nicole Hartwig
AU - Holm, Bettina Eide
AU - Heiden, Julie
AU - Slot, Ole
AU - Locht, Henning
AU - Jensen, Bente
AU - Lindegaard, Hanne
AU - Svendsen, Anders
AU - Nielsen, Christoffer Tandrup
AU - Jacobsen, Søren
AU - Theander, Elke
AU - Houen, Gunnar
N1 - Copyright © 2017 Elsevier B.V. All rights reserved.
PY - 2018/3
Y1 - 2018/3
N2 - Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. A characteristic feature of RA is the presence of anti-citrullinated protein antibodies (ACPA). Since ACPAs are highly specific for RA and are often present before the onset of RA symptoms, they have become valuable diagnostic and prognostic. As a result, several assays for detection of ACPAs exist, which vary in sensitivity and specificity. In this study, we analyzed the reactivity of RA sera to selected peptides by solid-phase immunoassays in order to develop an ACPA assay with improved sensitivity and specificity. ACPA levels were determined with respect to sensitivity and specificity in 332 serum samples using the newly developed peptide panel, which was compared to the commercial assays CCPlus (Eurodiagnostica) and CCP3.1 (Inova Diagnostics). A primary panel (peptides 814, 33062 and 33156) was identified, which obtained a sensitivity of 71%, while the complete peptide panel reacted with 79% of RA sera screened. Total specificities of 89% and 80% were obtained for the primary peptide panel and the complete peptide panel. Sensitivities for the commercial assays ranged between 71% and 76% and specificities between 88% and 90%. These findings indicate that the generated peptide panel is optimal for ACPA detection and able to compete with commercial available assays. Collectively, this study may contribute to characterize autoimmunity towards citrullinated proteins and to the development of new and improved diagnostic assays for detection of ACPA and determination of RA.
AB - Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. A characteristic feature of RA is the presence of anti-citrullinated protein antibodies (ACPA). Since ACPAs are highly specific for RA and are often present before the onset of RA symptoms, they have become valuable diagnostic and prognostic. As a result, several assays for detection of ACPAs exist, which vary in sensitivity and specificity. In this study, we analyzed the reactivity of RA sera to selected peptides by solid-phase immunoassays in order to develop an ACPA assay with improved sensitivity and specificity. ACPA levels were determined with respect to sensitivity and specificity in 332 serum samples using the newly developed peptide panel, which was compared to the commercial assays CCPlus (Eurodiagnostica) and CCP3.1 (Inova Diagnostics). A primary panel (peptides 814, 33062 and 33156) was identified, which obtained a sensitivity of 71%, while the complete peptide panel reacted with 79% of RA sera screened. Total specificities of 89% and 80% were obtained for the primary peptide panel and the complete peptide panel. Sensitivities for the commercial assays ranged between 71% and 76% and specificities between 88% and 90%. These findings indicate that the generated peptide panel is optimal for ACPA detection and able to compete with commercial available assays. Collectively, this study may contribute to characterize autoimmunity towards citrullinated proteins and to the development of new and improved diagnostic assays for detection of ACPA and determination of RA.
KW - Anti-Citrullinated Protein Antibodies/metabolism
KW - Arthritis, Rheumatoid/diagnosis
KW - Early Diagnosis
KW - Enzyme-Linked Immunosorbent Assay/methods
KW - Humans
KW - Peptides/chemical synthesis
KW - Predictive Value of Tests
KW - Prognosis
KW - Proteoglycans/chemical synthesis
KW - Sensitivity and Specificity
U2 - 10.1016/j.jim.2017.11.004
DO - 10.1016/j.jim.2017.11.004
M3 - Journal article
C2 - 29128424
SN - 0022-1759
VL - 454
SP - 6
EP - 14
JO - Journal of Immunological Methods
JF - Journal of Immunological Methods
ER -