Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
Clinical Rheumatology
Published in: Clinical Rheumatology 4/2020

01-04-2020 | Rheumatoid Arthritis | Original Article

Meta-analysis: diagnostic accuracy of the citrullinated peptides derived from fibrinogen and vimentin in rheumatoid arthritis

Authors: Xue Li, Zhenni Wang, Han Yi, Jun Xie, Naishuo Zhu

Published in: Clinical Rheumatology | Issue 4/2020

Login to get access

Abstract

Objectives

Anticitrullinated protein/peptide antibodies (ACPAs) have shown valuable effects in the diagnosis of rheumatoid arthritis (RA). Both fibrinogen and vimentin are significant antigens of ACPAs. This study evaluated the diagnostic performance of fibrinogen and vimentin peptides in RA.

Methods

We searched the PubMed, Embase, and Cochrane Library databases for studies published in English until January 2019 that evaluated the utility of the peptides of both vimentin and fibrinogen. The bivariate mixed-effects model and summary receiver operating characteristic (SROC) curve were used to estimate sensitivity and specificity across studies.

Results

Seven peptides from 19 studies were included. The pooled sensitivities of Fibα36–50, Fibα563–583, Fibα580–600, Fibα621–635, Fibβ36–52, Fibβ60–74, and Vim60–75 were 35%, 41%, 18%, 26%, 0.53%, 57%, and 44%, respectively. The pooled specificities of Fibα36–50, Fibα563–583, Fibα580–600, Fibα621–635, Fibβ36–52, Fibβ60–74, and Vim60–75 were 97%, 98%, 98%, 98%, 97%, 98%, and 98%, respectively. The SROC areas under the curve (AUCs) of Fibα36–50, Fibα563–583, Fibα580–600, Fibα621–635, Fibβ36–52, Fibβ60–74, and Vim60–75 were 0.92, 0.85, 0.64, 0.82, 0.91, 0.96, and 0.86, respectively.

Conclusion

Both fibrinogen and vimentin peptides have a high specificity but a relatively low sensitivity in diagnosing RA. The diagnostic accuracies of Fibβ60–74 and Fibβ36–52 were better than those of Vim60–75, Fibα36–50, and Fibα563–583, and all of them were better than that of Fibα621–635 and Fibα580–600.
Key Points
• Our study summarized the diagnostic accuracy of peptides derived from fibrinogen and vimentin and evaluated the diagnostic value of different peptides for RA patients.
• Both fibrinogen and vimentin peptides have a high specificity but a relatively low sensitivity in diagnosing RA.
Appendix
Available only for authorised users
Literature
1.
2.
Shi J, Knevel R, Suwannalai P et al (2011) Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage[J]. Proc Natl Acad Sci U S A 108(42):17372–17377PubMedPubMedCentral
3.
Trouw LA, Mahler M (2012) Closing the serological gap: promising novel biomarkers for the early diagnosis of rheumatoid arthritis. Autoimmun Rev 12(2):318–322PubMed
4.
Badillo-Soto MA, Rodriguez-Rodriguez M, Perez-Perez ME et al (2016) Potential protein targets of the peptidylarginine deiminase 2 and peptidylarginine deiminase 4 enzymes in rheumatoid synovial tissue and its possible meaning. Eur J Rheumatol 3(2):44–49PubMedPubMedCentral
5.
Trier NH, Holm BE, Slot O et al (2016) Physical characteristics of a citrullinated pro-filaggrin epitope recognized by anti-citrullinated protein antibodies in rheumatoid arthritis sera. PLoS One 11(12):e168542
6.
Takizawa Y, Suzuki A, Sawada T et al (2006) Citrullinated fibrinogen detected as a soluble citrullinated autoantigen in rheumatoid arthritis synovial fluids. Ann Rheum Dis 65(8):1013–1020PubMedPubMedCentral
7.
Malakoutikhah M, Gomara MJ, Gomez-Puerta JA et al (2011) The use of chimeric vimentin citrullinated peptides for the diagnosis of rheumatoid arthritis. J Med Chem 54(21):7486–7492PubMed
8.
Reed E, Jiang X, Kharlamova N et al (2016) Antibodies to carbamylated alpha-enolase epitopes in rheumatoid arthritis also bind citrullinated epitopes and are largely indistinct from anti-citrullinated protein antibodies. Arthritis Res Ther 18(1):96PubMedPubMedCentral
9.
Koivula MK, Heliovaara M, Rissanen H et al (2012) Antibodies binding to citrullinated telopeptides of type I and type II collagens and to mutated citrullinated vimentin synergistically predict the development of seropositive rheumatoid arthritis. Ann Rheum Dis 71(10):1666–1670PubMed
10.
Vander CB, Cantaert T, Nogueira L et al (2006) Diagnostic value of anti-human citrullinated fibrinogen ELISA and comparison with four other anti-citrullinated protein assays. Arthritis Res Ther 8(4):R122
11.
Bang H, Egerer K, Gauliard A et al (2007) Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. Arthritis Rheum 56(8):2503–2511PubMed
12.
Luime JJ, Colin EM, Hazes JM, Lubberts E (2010) Does anti-mutated citrullinated vimentin have additional value as a serological marker in the diagnostic and prognostic investigation of patients with rheumatoid arthritis? A systematic review. Ann Rheum Dis 69(2):337–344PubMed
13.
Moher D, Liberati A, Tetzlaff J et al (2010) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 8(5):336–341PubMed
14.
Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324PubMed
15.
Aletaha D, Neogi T, Silman AJ et al (2010) 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62(9):2569–2581PubMed
16.
Whiting P, Rutjes AW, Reitsma JB et al (2003) The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 3:25PubMedPubMedCentral
17.
Cheung MW, Vijayakumar R (2016) A guide to conducting a meta-analysis. Neuropsychol Rev 26(2):121–128PubMed
18.
McKenzie JE, Beller EM, Forbes AB (2016) Introduction to systematic reviews and meta-analysis. Respirology 21(4):626–637PubMed
19.
Jonsson MK, Hensvold AH, Hansson M et al (2018) The role of anti-citrullinated protein antibody reactivities in an inception cohort of patients with rheumatoid arthritis receiving treat-to-target therapy. Arthritis Res Ther:20(1)
20.
Cornillet M, Babos F, Magyar A et al (2018) Seropositivity and antibody profiling of patients are dramatically impacted by the features of peptides used as immunosorbents: a lesson from anti-citrullinated protein/peptide antibody. J Immunol 201(11):3211–3217PubMed
21.
Too CL, Murad S, Hansson M et al (2017) Differences in the spectrum of anti-citrullinated protein antibody fine specificities between Malaysian and Swedish patients with rheumatoid arthritis: implications for disease pathogenesis. Arthritis Rheum 69(1):58–69
22.
Cornillet M, Ajana S, Ruyssen-Witrand A et al (2016) Autoantibodies to human citrullinated fibrinogen and their subfamilies to the α36-50Cit and β60-74Cit fibrin peptides similarly predict radiographic damages: a prospective study in the French ESPOIR cohort of very early arthritides. Rheumatology (United Kingdom) 55(10):1859–1870
23.
Quirke AM, Perry E, Cartwright A, Kelly C, de Soyza A, Eggleton P, Hutchinson D, Venables PJ (2015) Bronchiectasis is a model for chronic bacterial infection inducing autoimmunity in rheumatoid arthritis[J]. Arthritis Rheum 67(9):2335–2342
24.
Kokkonen H, Brink M, Hansson M et al (2015) Associations of antibodies against citrullinated peptides with human leukocyte antigen-shared epitope and smoking prior to the development of rheumatoid arthritis[J]. Arthritis Res Ther 17:125PubMedPubMedCentral
25.
Fernandes-Cerqueira C, Ossipova E, Gunasekera S et al (2015) Targeting of anti-citrullinated protein/peptide antibodies in rheumatoid arthritis using peptides mimicking endogenously citrullinated fibrinogen antigens. Arthritis Res Ther 17(1)
26.
van Heemst J, Trouw LA, Nogueira L et al (2015) An investigation of the added value of an ACPA multiplex assay in an early rheumatoid arthritis setting[J]. Arthritis Res Ther 17:276PubMedPubMedCentral
27.
Janssen KM, de Smit MJ, Brouwer E et al (2015) Rheumatoid arthritis-associated autoantibodies in non-rheumatoid arthritis patients with mucosal inflammation: a case-control study[J]. Arthritis Res Ther 17:174PubMedPubMedCentral
28.
Nogueira L, Cornillet M, Singwe-Ngandeu M, Viatte S, Bas S, Gabay C, Serre G (2014) In Black Africans with rheumatoid arthritis, ACPA recognize citrullinated fibrinogen and the derived peptides alpha36-50Cit38,42 and beta60-74Cit60,72,74, like in Caucasians. Clin Immunol 152(1-2):58–64PubMed
29.
Cornillet M, Sebbag M, Verrouil E, Magyar A, Babos F, Ruyssen-Witrand A, Hudecz F, Cantagrel A, Serre G, Nogueira L (2014) The fibrin-derived citrullinated peptide beta60-74Cit(6)(0),(7)(2),(7)(4) bears the major ACPA epitope recognised by the rheumatoid arthritis-specific anticitrullinated fibrinogen autoantibodies and anti-CCP2 antibodies. Ann Rheum Dis 73(6):1246–1252PubMed
30.
Fisher BA, Bang SY, Chowdhury M et al (2014) Smoking, the HLA-DRB1 shared epitope and ACPA fine-specificity in Koreans with rheumatoid arthritis: evidence for more than one pathogenic pathway linking smoking to disease[J]. Ann Rheum Dis 73(4):741–747PubMed
31.
Lundberg K, Bengtsson C, Kharlamova N, Reed E, Jiang X, Kallberg H, Pollak-Dorocic I, Israelsson L, Kessel C, Padyukov L, Holmdahl R, Alfredsson L, Klareskog L (2013) Genetic and environmental determinants for disease risk in subsets of rheumatoid arthritis defined by the anticitrullinated protein/peptide antibody fine specificity profile. Ann Rheum Dis 72(5):652–658PubMed
32.
Goules JD, Goules AV, Tzioufas AG (2013) Fine specificity of anti-citrullinated peptide antibodies discloses a heterogeneous antibody population in rheumatoid arthritis[J]. Clin Exp Immunol 174(1):10–17PubMedPubMedCentral
33.
Brink M, Hansson M, Mathsson L, Jakobsson PJ, Holmdahl R, Hallmans G, Stenlund H, Rönnelid J, Klareskog L, Rantapää-Dahlqvist S (2013) Multiplex analyses of antibodies against citrullinated peptides in individuals prior to development of rheumatoid arthritis[J]. Arthritis Rheum 65(4):899–910PubMed
34.
Hansson M, Mathsson L, Schlederer T, et al (2012) Validation of a multiplex chip-based assay for the detection of autoantibodies against citrullinated peptides. Arthritis Res Ther 14(5)
35.
Iobagiu C, Magyar A, Nogueira L, Cornillet M, Sebbag M, Arnaud J, Hudecz F, Serre G (2011) The antigen specificity of the rheumatoid arthritis-associated ACPA directed to citrullinated fibrin is very closely restricted[J]. J Autoimmun 37(4):263–272PubMed
36.
van de Stadt LA, de Koning MH, van de Stadt RJ et al (2011) Development of the anti-citrullinated protein antibody repertoire prior to the onset of rheumatoid arthritis[J]. Arthritis Rheum 63(11):3226–3233PubMed
37.
Snir O, Widhe M, Hermansson M et al (2010) Antibodies to several citrullinated antigens are enriched in the joints of rheumatoid arthritis patients[J]. Arthritis Rheum 62(1):44–52PubMed
38.
Sebbag M, Moinard N, Auger I, Clavel C, Arnaud J, Nogueira L, Roudier J, Serre G (2006) Epitopes of human fibrin recognized by the rheumatoid arthritis-specific autoantibodies to citrullinated proteins. Eur J Immunol 36(8):2250–2263PubMed
39.
Sanmarti R, Graell E, Perez ML et al (2009) Diagnostic and prognostic value of antibodies against chimeric fibrin/filaggrin citrullinated synthetic peptides in rheumatoid arthritis[J]. Arthritis Res Ther 11(5):R135PubMedPubMedCentral
40.
Avino A, Gomara MJ, Malakoutikhah M et al (2012) Oligonucleotide-peptide conjugates: solid-phase synthesis under acidic conditions and use in ELISA assays. Molecules 17(12):13825–13843PubMedPubMedCentral
41.
Willemze A, van der Woude D, Ghidey W, Levarht EW, Stoeken-Rijsbergen G, Verduyn W, de Vries RR, Houwing-Duistermaat JJ, Huizinga TW, Trouw LA, Toes RE (2011) The interaction between HLA shared epitope alleles and smoking and its contribution to autoimmunity against several citrullinated antigens. Arthritis Rheum 63(7):1823–1832PubMed
42.
James EA, Rieck M, Pieper J et al (2014) Citrulline-specific Th1 cells are increased in rheumatoid arthritis and their frequency is influenced by disease duration and therapy. Arthritis Rheum 66(7):1712–1722
43.
Snir O, Rieck M, Gebe JA, Yue BB, Rawlings CA, Nepom G, Malmström V, Buckner JH (2011) Identification and functional characterization of T cells reactive to citrullinated vimentin in HLA-DRB1*0401-positive humanized mice and rheumatoid arthritis patients. Arthritis Rheum 63(10):2873–2883PubMedPubMedCentral
44.
Joshua V, Schobers L, Titcombe PJ et al (2016) Antibody responses to de novo identified citrullinated fibrinogen peptides in rheumatoid arthritis and visualization of the corresponding B cells. Arthritis Res Ther 18(1):284PubMedPubMedCentral
45.
Haro I, Gomara MJ, Perez ML et al (2011) Antibodies against beta-fibrin synthetic peptides: a study of their association with the immunogenetic background and disease course of rheumatoid arthritis patients. Eur J Med Chem 46(4):1095–1102PubMed
46.
Ytterberg AJ, Joshua V, Reynisdottir G, Tarasova NK, Rutishauser D, Ossipova E, Haj Hensvold A, Eklund A, Sköld CM, Grunewald J, Malmström V, Jakobsson PJ, Rönnelid J, Padyukov L, Zubarev RA, Klareskog L, Catrina AI (2015) Shared immunological targets in the lungs and joints of patients with rheumatoid arthritis: identification and validation[J]. Ann Rheum Dis 74(9):1772–1777PubMed
Metadata
Title
Meta-analysis: diagnostic accuracy of the citrullinated peptides derived from fibrinogen and vimentin in rheumatoid arthritis
Authors
Xue Li
Zhenni Wang
Han Yi
Jun Xie
Naishuo Zhu
Publication date
01-04-2020
Publisher
Springer London
Published in
Clinical Rheumatology / Issue 4/2020
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-019-04845-2

Other articles of this Issue 4/2020

Clinical Rheumatology 4/2020 Go to the issue

Brief Report

Annexin-A5 resistance and non-criteria antibodies for the diagnosis of seronegative antiphospholipid syndrome

Original Article

eHealth-supported decentralized multi-disciplinary care for gout involving rheumatology, pharmacy, and dietetics: proof-of-concept study

Case Based Review

Insights into the pathogenesis of catastrophic antiphospholipid syndrome. A case report of relapsing catastrophic antiphospholipid syndrome and review of the literature on ischemic colitis

Original Article

High frequency of nocturnal hypertension in lupus nephritis: should ABPM be implemented in usual practice?

Original Article

Evaluating the role of serum sclerostin as an indicator of activity and damage in Egyptian patients with rheumatoid arthritis: university hospital experience

Original Article

Disease activity–based management of rheumatoid arthritis in Dutch daily clinical practice has improved over the past decade
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits