Development of Autoantibodies in Patients with Very Early Arthritis – A Follow-up Study - OP 0097
Authors: Nell, Machold, Hoefler, Steiner, Smolen
Along with history and physical examination, assessment of autoantibody status (i.e. rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (CCP)) plays a prominent role in the early diagnosis of rheumatoid arthritis (RA). However, these auto-antibodies may be absent in very early RA, a setting that may confuse the diagnosis when the early clinical presentation is incomplete or atypical. Here, Nell et al explore the dynamics of auto-antibody seropositivity in patients with very early arthritis.
Methods:
200 patients with very early inflammatory arthritis, defined as symptoms less than 3 months in duration with at least one swollen joint and elevated inflammatory markers (ESR or CRP), were assessed at baseline for RA-associated auto-antibodies: IgM-RF by nephelometry; IgG-RF, IgA-RF, and anti-CCP by ELISA. Stability of baseline auto-antibodies was assessed in subjects who maintained a clinical picture consistent with RA during longitudinal follow-up.
Results:
Although only 35 patients (17.5%) met ACR classification criteria for RA at baseline, 102 patients (51%) had clinical RA at first follow-up. Only 82 of these were available at the second follow-up time point. The remaining 98 enrolled patients went on to express clinical phenotypes consistent with other inflammatory and non-inflammatory arthritides.
The mean observation time for follow-up was 32 months. IgM RF at a cut-off level of 50 U/ml was present in 45% of RA patients at baseline but only 38% at second follow-up. IgA-RF was present in 29% of RA patients at baseline but decreased to 27% at second follow-up. Anti-CCP antibodies were present in 41% of RA patients at baseline and increased to 49% at second follow-up. IgM-RF and anti-CCP antibodies, but not IgG-RF or IgA-RF, were significantly associated with the later development of radiographic erosions (p<0.01).
Conclusions:
In general, RA-associated auto-antibodies do not increase over time in very early arthritis patients who go on to develop a sustained clinical picture consistent with RA.
Editorial Comment:
These findings are slightly different from previous investigations showing that the prevalence of RF increases with disease duration, but that CCP antibody remains relatively stable. The reason for this discrepancy may be the inclusion of many patients who did not fulfill classification criteria for RA at the onset of symptoms. If only these patients had been included, then the prevalence of RF and CCP would have likely been higher at baseline. These results highlight the non-specific nature of auto-antibodies in patients with incomplete presentations. Importantly, the authors only present group prevalences, not the number of patients who were initial seropositive and become seronegative, or vice-versa. If an equal number of patients seroconverted as lost their auto-antibody response, then the group prevalence could equal out.