Open Access Highly Accessed Open Badges Research article

Anti-cyclic citrullinated peptide antibody titer predicts time to rheumatoid arthritis onset in patients with undifferentiated arthritis: results from a 2-year prospective study

Nicola Bizzaro1*, Elena Bartoloni2, Gabriella Morozzi3, Stefania Manganelli3, Valeria Riccieri4, Paola Sabatini5, Matteo Filippini6, Marilina Tampoia7, Antonella Afeltra8, Giandomenico Sebastiani9, Claudia Alpini10, Vittorio Bini11, Onelia Bistoni2, Alessia Alunno2, Roberto Gerli2 and the Forum Interdisciplinare per la Ricerca nelle Malattie Autoimmuni (FIRMA Group)

Author Affiliations

1 Laboratorio di Patologia Clinica, Ospedale San Antonio, 33028 Tolmezzo, Italy

2 Struttura di Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Università di Perugia, 06122 Perugia, Italy

3 Dipartimento di Scienze Mediche, Chirurgiche e Neuroscienze, Università degli Studi di Siena, 53100 Siena, Italy

4 Dip. di Medicina Interna e Specialità Mediche, Università Sapienza di Roma, 00185 Roma, Italy

5 UOC di Patologia Clinica, D.E.A. II Umberto I, 84014 Nocera Inferiore, Italy

6 Divisione di Reumatologia, Spedali Civili di Brescia, 25125 Brescia, Italy

7 Laboratorio di Patologia Clinica, Azienda Ospedaliera Universitaria, Policlinico di Bari, 70124 Bari, Italy

8 U.O.C. di Medicina Clinica e Reumatologia, Università Campus Bio-Medico, 00128 Roma, Italy

9 U.O.C. di Reumatologia, Azienda Ospedaliera San Camillo - Forlanini, 00151 Roma, Italy

10 S.C. Analisi Chimico Cliniche, Fondazione IRCCS Policlinico S.Matteo, 27100 Pavia, Italy

11 Dipartimento di Medicina Interna, Università di Perugia, 06122 Perugia, Italy

For all author emails, please log on.

Arthritis Research & Therapy 2013, 15:R16  doi:10.1186/ar4148

Published: 22 January 2013



The diagnostic, predictive and prognostic role of anti-cyclic citrullinated peptide (CCP) antibodies in rheumatoid arthritis (RA) patients is widely accepted. Moreover, detection of these antibodies in subjects presenting with undifferentiated arthritis (UA) is associated with a significant risk to develop the disease. On the other hand, clinical and prognostic significance of evaluating anti-CCP levels in subjects with inflammatory arthritis at disease onset has not been fully clarified. The goal of this prospective study is to analyze the value and prognostic significance of anti-CCP titer quantification in UA subjects.


Serial anti-CCP assays were measured in 192 consecutive patients presenting with UA lasting less than 12 weeks. Clinical and serological data and arthritis outcome were evaluated every 6 months until two years of follow-up.


Anti-CCP positivity, at both low and high titer, and arthritis of hand joints significantly predicted RA at two years, risk increasing in subjects with high anti-CCP titers at baseline. Moreover, time to RA diagnosis was shorter in patients with high anti-CCP2 titers at enrollment with respect to those with low antibody concentration.


Presence of anti-CCP antibodies, at both low and high concentration, is significantly associated with RA development in subjects with recent onset UA. However, time interval from the onset of the first symptoms to the fulfilment of the classification criteria appears to be directly related to the initial anti-CCP level.