Utility of testing for third-generation anticyclic citrullinated peptide (anti-CCP3) antibodies in individuals who present with new musculoskeletal symptoms but have a negative second-generation anticyclic citrullinated peptide (anti-CCP2) antibody test

Andrea Di Matteo; Kulveer Mankia; Leticia Garcia-Montoya; Sana Sharrack; Laurence Duquenne; Jacqueline L Nam; Michael Mahler; Paul Emery

doi:10.1136/rmdopen-2023-003927

Utility of testing for third-generation anticyclic citrullinated peptide (anti-CCP3) antibodies in individuals who present with new musculoskeletal symptoms but have a negative second-generation anticyclic citrullinated peptide (anti-CCP2) antibody test

RMD Open. 2024 Apr 10;10(2):e003927. doi: 10.1136/rmdopen-2023-003927.

Authors

Andrea Di Matteo^{1

2}, Kulveer Mankia^{1

2}, Leticia Garcia-Montoya^{1

2}, Sana Sharrack³, Laurence Duquenne^{1

2}, Jacqueline L Nam⁴, Michael Mahler⁵, Paul Emery^{6

2}

Affiliations

¹ Leeds Institute of Rheumatic and Musculoskeletal Disease, University of Leeds, Leeds, UK.
² NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
³ Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
⁴ Rheumatology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
⁵ Werfen Autoimmunity Technology Center, San Diego, California, USA.
⁶ Leeds Institute of Rheumatic and Musculoskeletal Disease, University of Leeds, Leeds, UK p.emery@leeds.ac.uk.

Abstract

Objectives: To investigate the role of third-generation anticyclic citrullinated peptide (anti-CCP3) antibodies in predicting progression to inflammatory arthritis (IA) in individuals with new musculoskeletal (MSK) symptoms and a negative second-generation anti-CCP antibody test (anti-CCP2-).

Methods: 469 anti-CCP2- individuals underwent baseline anti-CCP3 testing (QUANTA Lite CCP3; Inova Diagnostics) and received a post enrolment 12-month questionnaire. A rheumatologist confirmed or excluded diagnosis of IA. Univariable/multivariable analyses were performed to assess the value of anti-CCP3 in predicting IA development in these anti-CCP2- individuals.

Results: Only 16/469 (3.4%) anti-CCP2- individuals had a positive anti-CCP3 test. Of these 16 individuals, 4 developed IA. In addition, 61/469 (13.0%) anti-CCP2- individuals self-reported, to have developed, IA. Progression was confirmed in 43/61 of them (70.5%); of whom 30/43 (69.8%) and 13/43 (30.2%) were given a diagnosis of IA and rheumatoid arthritis (RA), respectively. In qualitative univariable analysis, anti-CCP3 positivity was associated with self-reported progression (p<0.01) and IA (p=0.03), but not with RA. Anti-CCP3 levels differed significantly between progressors and non-progressors (p<0.01) for all three categories. At the manufacturer's cut-off, OR for progression ranged from 2.4 (95% CI 0.5 to 18.6; RA) to 7.5 (95% CI 2.3 to 24.0; self-reported progression). Interestingly, when cut-offs for anti-CCP3 were optimised, lower values (≥5 units) significantly increased the OR for progression in all three categories. In multivariable analysis, anti-CCP3 positivity at the manufacturer's cut-off did not remain associated with IA progression, while this lower cut-off value (≥5 units) was associated with diagnosis of RA (p=0.02).

Conclusions: Anti-CCP3 testing could improve the prediction of IA development in anti-CCP2- individuals with new MSK symptoms.

Keywords: Anti-Citrullinated Protein Antibodies; Antibodies; Arthritis, Rheumatoid.

MeSH terms

Anti-Citrullinated Protein Antibodies*
Arthritis, Rheumatoid / diagnosis
Autoantibodies*
Humans

Substances

Anti-Citrullinated Protein Antibodies
Autoantibodies