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

Trier, Nicole Hartwig; Holm, Bettina Eide; Heiden, Julie; Slot, Ole; Locht, Henning; Jensen, Bente; Lindegaard, Hanne; Svendsen, Anders; Nielsen, Christoffer Tandrup and Jacobsen, Søren, et al. (2017) In Journal of Immunological Methods
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... (More)

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.

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keywords
Anti-citrullinated protein antibodies, Cyclic citrullinated peptides, Rheumatoid arthritis, Streptavidin capture enzyme-linked immunosorbent assay, Synthetic peptides
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Journal of Immunological Methods
publisher
Elsevier
external identifiers
  • scopus:85034859452
ISSN
0022-1759
DOI
10.1016/j.jim.2017.11.004
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English
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yes
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61b061a3-2e02-4ef6-ba69-ba8b50c86d55
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2017-12-28 14:27:23
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2018-01-07 12:29:53
@article{61b061a3-2e02-4ef6-ba69-ba8b50c86d55,
  abstract     = {<p>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.</p>},
  author       = {Trier, Nicole Hartwig and Holm, Bettina Eide and Heiden, Julie and Slot, Ole and Locht, Henning and Jensen, Bente and Lindegaard, Hanne and Svendsen, Anders and Nielsen, Christoffer Tandrup and Jacobsen, Søren and Theander, Elke and Houen, Gunnar},
  issn         = {0022-1759},
  keyword      = {Anti-citrullinated protein antibodies,Cyclic citrullinated peptides,Rheumatoid arthritis,Streptavidin capture enzyme-linked immunosorbent assay,Synthetic peptides},
  language     = {eng},
  month        = {11},
  publisher    = {Elsevier},
  series       = {Journal of Immunological Methods},
  title        = {The use of synthetic peptides for detection of anti-citrullinated protein antibodies in rheumatoid arthritis},
  url          = {http://dx.doi.org/10.1016/j.jim.2017.11.004},
  year         = {2017},
}