BACKGROUND: Anti-citrullinated protein antibodies (ACPA) are associated with increased risk for rheumatoid arthritis. OBJECTIVE: To investigate the effect of the presence and levels of ACPA on arthritis development in patients with arthralgia. METHODS: Patients with arthralgia positive for ACPA or IgM rheumatoid factor (IgM-RF) were tested for the shared epitope (SE) and were prospectively followed up for at least 12 months. Absence of clinical arthritis at inclusion and arthritis development during follow-up were independently confirmed by two investigators. Cox regression hazard analyses were used to calculate hazard ratios (HRs) for arthritis development. RESULTS: 147 patients with arthralgia were included (50 ACPA positive, 52 IgM-RF positive and 45 positive for both antibodies). After a median follow-up of 28 months (interquartile range (IQR) 19-39), 29 patients developed arthritis in a median of 4 (IQR 3-6) joints and 26 (90%) of these were ACPA positive. The presence of ACPA (HR = 6.0; 95% confidence interval (95% CI) 1.8 to 19.8; p = 0.004), but not of IgM-RF (HR = 1.4, 95% CI 0.6 to 3.1) nor the SE (HR = 1.5, 95% CI 0.7 to 3.0), was associated with arthritis development. Within the group of ACPA-positive patients, the risk for arthritis was enhanced by the presence of IgM-RF (HR = 3.0; 95% CI 1.4 to 6.9; p = 0.01) and high ACPA levels (HR = 1.7; 95% CI 1.1 to 2.5; p = 0.008), but not the SE (HR = 1.0; 95% CI 0.5 to 2.1; p = 1.0). CONCLUSION: In patients with arthralgia the presence of ACPA (but not of IgM-RF or SE) predicts arthritis development. The risk in ACPA-positive patients may be further increased by the concomitant presence of IgM-RF or high levels of ACPA.
BACKGROUND: Anti-citrullinated protein antibodies (ACPA) are associated with increased risk for rheumatoid arthritis. OBJECTIVE: To investigate the effect of the presence and levels of ACPA on arthritis development in patients with arthralgia. METHODS:Patients with arthralgia positive for ACPA or IgM rheumatoid factor (IgM-RF) were tested for the shared epitope (SE) and were prospectively followed up for at least 12 months. Absence of clinical arthritis at inclusion and arthritis development during follow-up were independently confirmed by two investigators. Cox regression hazard analyses were used to calculate hazard ratios (HRs) for arthritis development. RESULTS: 147 patients with arthralgia were included (50 ACPA positive, 52 IgM-RF positive and 45 positive for both antibodies). After a median follow-up of 28 months (interquartile range (IQR) 19-39), 29 patients developed arthritis in a median of 4 (IQR 3-6) joints and 26 (90%) of these were ACPA positive. The presence of ACPA (HR = 6.0; 95% confidence interval (95% CI) 1.8 to 19.8; p = 0.004), but not of IgM-RF (HR = 1.4, 95% CI 0.6 to 3.1) nor the SE (HR = 1.5, 95% CI 0.7 to 3.0), was associated with arthritis development. Within the group of ACPA-positive patients, the risk for arthritis was enhanced by the presence of IgM-RF (HR = 3.0; 95% CI 1.4 to 6.9; p = 0.01) and high ACPA levels (HR = 1.7; 95% CI 1.1 to 2.5; p = 0.008), but not the SE (HR = 1.0; 95% CI 0.5 to 2.1; p = 1.0). CONCLUSION: In patients with arthralgia the presence of ACPA (but not of IgM-RF or SE) predicts arthritis development. The risk in ACPA-positive patients may be further increased by the concomitant presence of IgM-RF or high levels of ACPA.
Authors: Francesca Barone; Saba Nayar; Joana Campos; Thomas Cloake; David R Withers; Kai-Michael Toellner; Yang Zhang; Lynette Fouser; Benjamin Fisher; Simon Bowman; Javier Rangel-Moreno; Maria de la Luz Garcia-Hernandez; Troy D Randall; Davide Lucchesi; Michele Bombardieri; Costantino Pitzalis; Sanjiv A Luther; Christopher D Buckley Journal: Proc Natl Acad Sci U S A Date: 2015-08-18 Impact factor: 11.205
Authors: Jeffrey A Sparks; Maura D Iversen; Rachel Miller Kroouze; Taysir G Mahmoud; Nellie A Triedman; Sarah S Kalia; Michael L Atkinson; Bing Lu; Kevin D Deane; Karen H Costenbader; Robert C Green; Elizabeth W Karlson Journal: Contemp Clin Trials Date: 2014-08-20 Impact factor: 2.226
Authors: Julia A Ford; Xinyi Liu; Allison A Marshall; Alessandra Zaccardelli; Maria G Prado; Charlene Wiyarand; Bing Lu; Elizabeth W Karlson; Peter H Schur; Kevin D Deane; Jeffrey A Sparks Journal: Arthritis Care Res (Hoboken) Date: 2019-12 Impact factor: 4.794
Authors: Elizabeth W Karlson; Dirkjan van Schaardenburg; Annette H van der Helm-van Mil Journal: Rheumatology (Oxford) Date: 2014-08-04 Impact factor: 7.580