Different properties of ACPA and IgM-RF derived from a large dataset: further evidence of two distinct autoantibody systems

IntroductionThe aim of this study was to examine seroconversion and the relationship with age and inflammation of autoantibodies in a large group of patients attending an outpatient rheumatology clinic.MethodsLevels of antibodies to citrullinated proteins/peptides (ACPAs) and IgM rheumatoid factor (IgM-RF) were determined in 22,427 samples collected from 18,658 patients. The diagnosis was derived from a diagnosis registration system. The degree of seroconversion in repeated samples and the correlation of levels with age and inflammatory markers were determined for ACPA and IgM-RF in rheumatoid arthritis (RA) and non-RA patients.ResultsSeventy-one percent of RA patients (n = 1,524) were ACPA-positive and 53% were IgM-RF-positive; in non-RA patients (n = 2,245), the corresponding values were 2% and 4%, respectively. In patients with at least two samples (n = 3,769), ACPA status was more stable than IgM-RF status in RA patients. ACPA- or IgM-RF-negative non-RA patients seldom became positive. ACPA positivity was unrelated to age in both RA and non-RA patients. IgM-RF positivity was unrelated to age in RA patients; however, it increased with age in non-RA patients. The correlation between autoantibody levels and inflammatory markers was low in general and was somewhat higher for IgM-RF than for ACPA.ConclusionsACPA status is more stable in time and with increasing age than IgM-RF status, further establishing its role as a disease-specific marker. ACPA and IgM-RF levels are only moderately correlated with markers of inflammation.

[1]  L. Klareskog,et al.  Longitudinal analysis of citrullinated protein/peptide antibodies (anti-CP) during 5 year follow up in early rheumatoid arthritis: anti-CP status predicts worse disease activity and greater radiological progression , 2005, Annals of the rheumatic diseases.

[2]  G. Burmester,et al.  Rheumatoid factor revisited , 2004, Current opinion in rheumatology.

[3]  D. Kimpel Meta-analysis: Diagnostic Accuracy of Anti–Cyclic Citrullinated Peptide Antibody and Rheumatoid Factor for Rheumatoid Arthritis , 2008 .

[4]  B. Dijkmans,et al.  Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. , 2004, Arthritis and rheumatism.

[5]  B. Dijkmans,et al.  Increased levels of C-reactive protein in serum from blood donors before the onset of rheumatoid arthritis. , 2004, Arthritis and rheumatism.

[6]  T. Matsui,et al.  Diagnostic utility of anti-cyclic citrullinated peptide antibodies for very early rheumatoid arthritis. , 2006, The Journal of rheumatology.

[7]  T. Strandberg,et al.  Filaggrin related antibodies among the aged , 2003, Annals of the Rheumatic Diseases.

[8]  C. Alessandri,et al.  Decrease of anti-cyclic citrullinated peptide antibodies and rheumatoid factor following anti-TNFα therapy (infliximab) in rheumatoid arthritis is associated with clinical improvement , 2004, Annals of the rheumatic diseases.

[9]  R. Caporali,et al.  Predictive Value of Antibodies to Citrullinated Peptides and Rheumatoid Factors in Anti‐TNF‐α Treated Patients , 2007, Annals of the New York Academy of Sciences.

[10]  G Strandberg,et al.  Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project) , 2004, Annals of the rheumatic diseases.

[11]  P. Schur,et al.  Quantifying anti-cyclic citrullinated peptide titres: clinical utility and association with tobacco exposure in patients with rheumatoid arthritis , 2008, Annals of the rheumatic diseases.

[12]  L. Alfredsson,et al.  Immunity to citrullinated proteins in rheumatoid arthritis. , 2008, Annual review of immunology.

[13]  B. Dijkmans,et al.  IgM-rheumatoid factor, anti-cyclic citrullinated peptide, and anti-citrullinated human fibrinogen antibodies decrease during treatment with the tumor necrosis factor blocker infliximab in patients with rheumatoid arthritis. , 2008, The Journal of rheumatology.

[14]  A. Zwinderman,et al.  Clinical significance of rheumatoid factors in early rheumatoid arthritis: results of a follow up study. , 1992, Annals of the rheumatic diseases.

[15]  P. Sarzi-Puttini,et al.  Adalimumab clinical efficacy is associated with rheumatoid factor and anti-cyclic citrullinated peptide antibody titer reduction: a one-year prospective study , 2005, Arthritis research & therapy.

[16]  B. Dijkmans,et al.  Differential response of the rheumatoid factor and anticitrullinated protein antibodies during adalimumab treatment in patients with rheumatoid arthritis. , 2008, The Journal of rheumatology.

[17]  F. V. D. van den Hoogen,et al.  Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. , 1998, The Journal of clinical investigation.

[18]  R. Caporali,et al.  Autoantibody profile in rheumatoid arthritis during long-term infliximab treatment , 2004, Arthritis research & therapy.

[19]  S. van der Linden,et al.  Rheumatoid factor measured by fluoroimmunoassay: a responsive measure of rheumatoid arthritis disease activity that is associated with joint damage , 2002, Annals of the rheumatic diseases.

[20]  H. Heinzl,et al.  Autoantibody profiling in patients with very early rheumatoid arthritis: a follow-up study , 2009, Annals of the rheumatic diseases.

[21]  Y. Goekoop-Ruiterman,et al.  DAS-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis , 2009, Annals of the rheumatic diseases.

[22]  F. Breedveld,et al.  The relation between class-specific serum rheumatoid factors and age in the general population. , 1993, British journal of rheumatology.

[23]  M. Dougados,et al.  Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review , 2005, Annals of the rheumatic diseases.