The use of synthetic peptides for detection of anti-citrullinated protein antibodies in rheumatoid arthritis

Nicole Hartwig Trier; Bettina Eide Holm; Julie Heiden; Ole Slot; Henning Locht; Bente Jensen; Hanne Lindegaard; Anders Svendsen; Christoffer Tandrup Nielsen; Søren Jacobsen; Elke Theander; Gunnar Houen

doi:10.1016/j.jim.2017.11.004

The use of synthetic peptides for detection of anti-citrullinated protein antibodies in rheumatoid arthritis

Nicole Hartwig Trier, Bettina Eide Holm, Julie Heiden, Ole Slot, Henning Locht, Bente Jensen, Hanne Lindegaard, Anders Svendsen, Christoffer Tandrup Nielsen, Søren Jacobsen, Elke Theander, Gunnar Houen

Department of Clinical Medicine

10 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Immunological Methods
Volume	454
Pages (from-to)	6-14
ISSN	0022-1759
DOIs	https://doi.org/10.1016/j.jim.2017.11.004
Publication status	Published - Mar 2018

Keywords

Anti-Citrullinated Protein Antibodies/metabolism
Arthritis, Rheumatoid/diagnosis
Early Diagnosis
Enzyme-Linked Immunosorbent Assay/methods
Humans
Peptides/chemical synthesis
Predictive Value of Tests
Prognosis
Proteoglycans/chemical synthesis
Sensitivity and Specificity

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10.1016/j.jim.2017.11.004

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title = "The use of synthetic peptides for detection of anti-citrullinated protein antibodies in rheumatoid arthritis",

abstract = "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.",

keywords = "Anti-Citrullinated Protein Antibodies/metabolism, Arthritis, Rheumatoid/diagnosis, Early Diagnosis, Enzyme-Linked Immunosorbent Assay/methods, Humans, Peptides/chemical synthesis, Predictive Value of Tests, Prognosis, Proteoglycans/chemical synthesis, Sensitivity and Specificity",

author = "Trier, {Nicole Hartwig} and Holm, {Bettina Eide} and Julie Heiden and Ole Slot and Henning Locht and Bente Jensen and Hanne Lindegaard and Anders Svendsen and Nielsen, {Christoffer Tandrup} and S{\o}ren Jacobsen and Elke Theander and Gunnar Houen",

year = "2018",

month = mar,

doi = "10.1016/j.jim.2017.11.004",

language = "English",

volume = "454",

pages = "6--14",

journal = "Journal of Immunological Methods",

issn = "0022-1759",

publisher = "Elsevier",

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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

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 -

The use of synthetic peptides for detection of anti-citrullinated protein antibodies in rheumatoid arthritis

Abstract

Keywords

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