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14-06-2018 | Systemic lupus erythematosus | Article

Anti-carbamylated protein antibodies as a new biomarker of erosive joint damage in systemic lupus erythematosus

Journal: Arthritis Research & Therapy

Authors: Fulvia Ceccarelli, Carlo Perricone, Tania Colasanti, Laura Massaro, Enrica Cipriano, Monica Pendolino, Francesco Natalucci, Riccardo Mancini, Francesca Romana Spinelli, Guido Valesini, Fabrizio Conti, Cristiano Alessandri

Publisher: BioMed Central

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Abstract

Background

The application of more sensitive imaging techniques, such as ultrasonography (US), changed the concept of non-erosive arthritis in systemic lupus erythematosus (SLE), underlining the need for biomarkers to identify patients developing the erosive phenotype. Anti-citrullinated peptide antibodies (ACPA), associated with erosions in inflammatory arthritis, have been identified in about 50% of patients with SLE with erosive arthritis. More recently, anti-carbamylated proteins antibodies (anti-CarP) have been associated with erosive damage in rheumatoid arthritis. We aimed to assess the association between anti-CarP and erosive damage in a large SLE cohort with joint involvement.

Methods

We evaluated 152 patients (male/female patients 11/141; median age 46 years, IQR 16; median disease duration 108 months, IQR 168). All patients underwent blood draw to detect rheumatoid factor (RF) and ACPA (commercial enzyme-linked immunosorbent assay (ELISA) kit), and anti-CarP (“home-made” ELISA, cutoff 340 aU/mL). The bone surfaces of the metacarpophalangeal and proximal interphalangeal joints were assessed by US: the presence of erosions was registered as a dichotomous value (0/1), obtaining a total score (0–20).

Results

The prevalence of anti-CarP was 28.3%, similar to RF (27.6%) and significantly higher than ACPA (11.2%, p = 0.003). Erosive arthritis was identified in 25.6% of patients: this phenotype was significantly associated with anti-CarP (p = 0.004). Significant correlation between anti-CarP titer and US erosive score was observed (r = 0.2, p = 0.01).

Conclusions

Significant association was identified between anti-CarP and erosive damage in SLE-related arthritis, in terms of frequency and severity, suggesting that these antibodies can represent a biomarker of severity in patients with SLE with joint involvement.
Literature
1.
Ceccarelli F, Perricone C, Cipriano E, Massaro L, Natalucci F, Capalbo G, Leccese I, Bogdanos D, Spinelli FR, Alessandri C, Valesini G, Conti F. Joint involvement in systemic lupus erythematosus: from pathogenesis to clinical assessment. Semin Arthritis Rheum. 2017;47:53–64.CrossRefPubMed
2.
Ball EM, Bell AL. Lupus arthritis—do we have a clinically useful classification? Rheumatology (Oxford). 2012;51:771–9.CrossRef
3.
Ceccarelli F, Massaro L, Perricone C, Pendolino M, Cipriano E, Truglia S, Miranda F, Spinelli FR, Alessandri C, Valesini G, Conti F. Jaccoud's arthropathy in systemic lupus erythematosus: clinical, laboratory and ultrasonographic features. Clin Exp Rheumatol. 2017;35:674–7.PubMed
4.
Piga M, Saba L, Gabba A, Congia M, Balestrieri A, Mathieu A, Cauli A. Ultrasonographic assessment of bone erosions in the different subtypes of systemic lupus erythematosus arthritis: comparison with computed tomography. Arthritis Res Ther. 2016;18:222.CrossRefPubMedPubMedCentral
5.
Østergaard M, Pedersen SJ, Døhn UM. Imaging in rheumatoid arthritis--status and recent advances for magnetic resonance imaging, ultrasonography, computed tomography and conventional radiography. Best Pract Res Clin Rheumatol. 2008;22:1019–44.CrossRefPubMed
6.
Delle Sedie A, Riente L, Scire CA, Iagnocco A, Filippucci E, Meenagh G, et al. Ultrasound imaging for the rheumatologist. XXIV. Sonographic evaluation of wrist and hand joint and tendon involvement in systemic lupus erythematosus. Clin Exp Rheumatol. 2009;27:897–901.PubMed
7.
Gabba A, Piga M, Vacca A, Porru G, Garau P, Cauli A, et al. Joint and tendon involvement in systemic lupus erythematosus: an ultrasound study of hands and wrists in 108 patients. Rheumatology (Oxford). 2012;51:2278–85.CrossRef
8.
Wright S, Filippucci E, Grassi W, Grey A, Bell A. Hand arthritis in systemic lupus erythematosus: an ultrasound pictorial essay. Lupus. 2006;15:501–6.CrossRefPubMed
9.
Mediwake R, Isenberg DA, Schellekens GA, van Venrooij WJ. Use of anti-citrullinated peptide and anti-RA33 antibodies in distinguishing erosive arthritis in patients with systemic lupus erythematosus and rheumatoid arthritis. Ann Rheum Dis. 2001;60:67.CrossRefPubMedPubMedCentral
10.
Amezcua-Guerra LM, Marquez-Velasco R, Bojalil R. Erosive arthritis in systemic lupus erythematosus is associated with high serum C-reactive protein and anti-cyclic citrullinated peptide antibodies. Inflamm Res. 2008;57:555–7.CrossRefPubMed
11.
Chan MT, Owen P, Dunphy J, Cox B, Carmichael C, Korendowych E, et al. Associations of erosive arthritis with anti-cyclic citrullinated peptide antibodies and MHC Class II alleles in systemic lupus erythematosus. J Rheumatol. 2008;35:77–83.PubMed
12.
Budhram A, Chu R, Rusta-Sallehy S, et al. Anti-cyclic citrullinated peptide antibody as a marker of erosive arthritis in patients with systemic lupus erythematosus: A systematic review and meta-analysis. Lupus. 2014;23:1156–63.CrossRefPubMed
13.
Shi J, van de Stadt LA, Levarht EW, et al. Anti-carbamylated protein (anti-CarP) antibodies precede the onset of rheumatoid arthritis. Ann Rheum Dis. 2014;73:780–3.CrossRefPubMed
14.
Shi J, van de Stadt LA, Levarht EW, et al. Anti-carbamylated protein antibodies are present in arthralgia patients and predict the development of rheumatoid arthritis. Arthritis Rheum. 2013;65:911–5.CrossRefPubMed
15.
van Delft MAM, Verheul MK, Burgers LE, VFAM D, van der Helm-van Mil AHM, van der Woude D, Huizinga TWJ, REM T, Trouw LA. The isotype and IgG subclass distribution of anti-carbamylated protein antibodies in rheumatoid arthritis patients. Arthritis Res Ther. 2017;19:190.CrossRefPubMedPubMedCentral
16.
Truchetet ME, Dublanc S, Barnetche T, Vittecoq O, Mariette X, Richez C, Blanco P, Mahler M, Contin-Bordes C, Schaeverbeke T, Fédération Hospitalo-Universitaire ACRONIM. Association of the presence of anti-carbamylated protein antibodies in early arthritis with a poorer clinical and radiologic outcome: data from the French ESPOIR cohort. Arthritis Rheumatol. 2017;69:2292–302.CrossRefPubMed
17.
Mastrangelo A, Colasanti T, Barbati C, Pecani A, Sabatinelli D, Pendolino M, Truglia S, Massaro L, Mancini R, Miranda F, Spinelli FR, Conti F, Alessandri C. The role of posttranslational protein modifications in rheumatological diseases: focus on RHEUMATOID ARTHRITIS. J Immunol Res. 2015;2015:712490.CrossRefPubMedPubMedCentral
18.
Pecani A, Alessandri C, Spinelli FR, et al. Prevalence, sensitivity and specificity of antibodies against carbamylated proteins in a monocentric cohort of patients with rheumatoid arthritis and other autoimmune rheumatic diseases. Arthritis Res Ther. 2016;18:276.CrossRefPubMedPubMedCentral
19.
Ziegelasch M, van Delft MA, Wallin P, et al. Antibodies against carbamylated proteins and cyclic citrullinated peptides in systemic lupus erythematosus: results from two well-defined European cohorts. Arthritis Res Ther. 2016;18:289.CrossRefPubMedPubMedCentral
20.
Massaro L, Ceccarelli F, Colasanti T, Pendolino M, Perricone C, Cipriano E, Natalucci F, Capalbo G, Lucchetti R, Pecani A, Vomero M, Mancini R, Spinelli FR, Alessandri C, Valesini G, Conti F. Anti-carbamylated protein antibodies in systemic lupus erythematosus patients with articular involvement. Lupus. 2018 Jan;27(1):105–11.CrossRefPubMed
21.
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725.CrossRefPubMed
22.
Cipriano E, Ceccarelli F, Massaro L, Spinelli FR, Alessandri C, Perricone C, Valesini G, Conti F. Joint involvement in patients affected by systemic lupus erythematosus: application of the swollen to tender joint count ratio. Reumatismo. 2015;67:62–7.CrossRefPubMed
23.
Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002;29:288–91.PubMed
24.
Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M, et al. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum. 1996;39:363–9.CrossRefPubMed
25.
Shi J, Knevel R, Suwannalai P, et al. Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage. Proc Natl Acad Sci U S A. 2011;108:17372–7.CrossRefPubMedPubMedCentral
26.
Backhaus M, Burmester GR, Gerber T, et al. Guidelines for musculoskeletal ultrasound in rheumatology. Ann Rheum Dis. 2001;60:641–9.CrossRefPubMedPubMedCentral
27.
Wakefield RJ, Balint PV, Szkudlarek M, et al. Musculoskeletal ultrasound including definitions for ultrasonographic pathology. J Rheumatol. 2005;32:2485–7.PubMed
28.
Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159–74.CrossRefPubMed
29.
Ceccarelli F, Perricone C, Borgiani P, Ciccacci C, Rufini S, Cipriano E, Alessandri C, Spinelli FR, Sili Scavalli A, Novelli G, Valesini G, Conti F. Genetic factors in systemic lupus erythematosus: contribution to disease phenotype. J Immunol Res. 2015;2015:745647.CrossRefPubMedPubMedCentral
30.
Warchol T, Lianeri M, Lacki JK, Olesińska M, Jagodziński PP. ITGAM Arg77His is associated with disease susceptibility, arthritis, and renal symptoms in systemic lupus erythematosus patients from a sample of the Polish population. DNA Cell Biol. 2011;30:33–8.CrossRefPubMed
31.
de Azevêdo SJ, Monteiro Fernandes K, Trés Pancotto JA, et al. Vitamin D receptor (VDR) gene polymorphisms and susceptibility to systemic lupus erythematosus clinical manifestations. Lupus. 2013;22:1110–7.CrossRef
32.
Ciccacci C, Perricone C, Ceccarelli F, Rufini S, Di Fusco D, Alessandri C, Spinelli FR, Cipriano E, Novelli G, Valesini G, Borgiani P, Conti F. A multilocus genetic study in a cohort of Italian SLE patients confirms the association with STAT4 gene and describes a new association with HCP5 gene. PLoS One. 2014;9:e111991.CrossRefPubMedPubMedCentral
33.
Conigliaro P, Chimenti MS, Triggianese P, Sunzini F, Novelli L, Perricone C, Perricone R. Autoantibodies in inflammatory arthritis. Autoimmun Rev. 2016;15:673–83.CrossRefPubMed
34.
Catrina AI, Svensson CI, Malmström V, Schett G, Klareskog L. Mechanisms leading from systemic autoimmunity to joint-specific disease in rheumatoid arthritis. Nat Rev Rheumatol. 2017;13:79–86.CrossRefPubMed
35.
Mistry P, Kaplan MJ. Cell death in the pathogenesis of systemic lupus erythematosus and lupus nephritis. Clin Immunol. 2017;185:59–73.CrossRefPubMed
36.
Backhaus M, Kamradt T, Sandrock D, Loreck D, Fritz J, Wolf KJ, Raber H, Hamm B, Burmester GR, Bollow M. Arthritis of the finger joints: a comprehensive approach comparing conventional radiography, scintigraphy, ultrasound, and contrast-enhanced magnetic resonance imaging. Arthritis Rheum. 1999;42:1232–45.CrossRefPubMed
37.
Szkudlarek M, Narvestad E, Klarlund M, Court-Payen M, Thomsen HS, Østergaard M. Ultrasonography of the metatarsophalangeal joints in rheumatoid arthritis: comparison with magnetic resonance imaging, conventional radiography, and clinical examination. Arthritis Rheum. 2004;50:2103–12.CrossRefPubMed
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