Article Text

AB0111 Development of anti–citrullinated protein antibody and rheumatoid factor isotypes in relation to smoking prior to the onset of rheumatoid arthritis
  1. W. Bos1,
  2. L. van de Stadt2,
  3. A. Sohrabian3,
  4. J. Ronnelid3,
  5. D. van Schaardenburg1,1
  1. 1Rheumatology, VU Medical Center
  2. 2Rheumatology, Reade, Amsterdam, Netherlands
  3. 3Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden


Background We and others have previously shown that IgG anti–citrullinated protein antibody (ACPA) and rheumatoid factor (RF) precede the development of RA.1, 2 Furthermore, it was shown that other isotypes of ACPA (IgA, and to lesser extent the IgM isotype) also predate the onset of RA.3 Moreover, smoking has been linked to the development of IgA ACPA in the preclinical phase.3

Objectives To further assess the relationship between ACPA and RF isotypes and smoking in preclinical RA.

Methods Multiple consecutive serum samples from 30 RA patients who had donated blood before disease onset were available for analysis. Per patient, 3 sequential pre-RA serum samples were selected and were tested for IgM, IgA and IgG ACPA and RF isotypes as described previously.3 Smoking status (current or past smoker versus never smoked) was obtained retrospectively by chart review and was available for 24 patients.

Results For IgA ACPA, 57% of the initial samples was positive. This percentage increased tot 75% in the last pre-diagnosis sample. All but one patient was positive for IgG ACPA at all time points. For IgM ACPA, only 20% of patients were initially positive, this increased to 43 % in the last pre-diagnosis sample (table 1). The median ACPA levels rose from 11 to 21, 24 to 394 and 32 to 50 AU/ml for IgA, IgG and IgM, respectively (p 0,07, 0,002 and 0,07, respectively [Kruskal Wallis Test]).

For RF, 67% of the initial samples were positive for IgA, and 13% and 47% for IgG and IgM, respectively. These percentages increased in time to 87%, 37% and 83% of patients, respectively(table 1). The median RF levels rose from 15 to 47, 10 to 29 and 5 to 39 AU/ml for IgA, IgG and IgM, respectively (p 0.04, 0.009 and 0.002, respectively [Kruskal Wallis Test]).

Conclusions In the preclinical phase of RA, IgG ACPA comes first, followed by IgA, and later by IgM. For RF the IgG subtype seems to appear after IgA and IgM. Furthermore, ACPA and RF levels of all isotypes rise over time prior to the clinical diagnosis of RA. Finally, smoking seems to influence both IgA APCA and IgA RF levels, which is in line with the hypothesis that smoking induces or augments an IgA response in the lungs. These data are in line with earlier studies3 and suggest an ongoing anti-citrulline immune stimulation in preclinical RA patients, which does not necessarily start in mucosa-associated lymphoid tissue.

  1. Rantapää-Dahlqvist et al. Arthritis Rheum 2003, 48:2741-2749.

  2. Nielen et al Arthritis Rheum 2004, 50:380-386.

  3. Kokkonen et al. Arthritis Research & Therapy 2011, 13:R13

Disclosure of Interest None Declared

Statistics from

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.