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  • Review Article
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The influence of ACPA status and characteristics on the course of RA

Abstract

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, and affects 0.5–1% of the population. Although it poses a considerable health problem, relatively little remains known about the disease pathogenesis and etiology. In the past decade, anti-citrullinated protein antibodies (ACPA) have emerged as suspects in the development and/or progression of RA. Citrullinated proteins—containing the amino acid citrulline, generated post-translationally from arginine—are found in the joints of patients with RA, but are not specific for the disease. This situation contrasts with the presence of ACPA, which are mostly found in individuals with RA. Intriguingly, ACPA can also be found in individuals before symptom onset. In these instances the ACPA response seems to be in its infancy, recognizing only a few citrullinated antigens and not using the full isotype repertoire. These characteristics of the ACPA response mature before clinical disease precipitates. Evidence is emerging that ACPA status can further characterize the heterogeneous RA phenotype, not only with respect to outcome, but perhaps also with respect to intervention. This Review summarizes the evolution of the ACPA response and its putative role in disease pathogenesis, as well as its relationship with clinical phenotype and diagnostic potential.

Key Points

  • The identification of anti-citrullinated protein antibodies (ACPA) has resulted in the identification of a subset of patients with RA with a more homogeneous outcome

  • ACPA are highly specific for RA and can be present years before the first clinical sign of the disease

  • Maturation of the ACPA response is associated with the emergence of clinical symptoms and the transition to RA

  • The presence of ACPA in RA is associated with greater radiological joint damage and with different response to therapy

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Figure 1: ACPA production by B cells can be stimulated by autoreactive T cells.
Figure 2: Fine specificity and isotype profiles are important characteristics of an ACPA response.
Figure 3: The maturation of the anti-citrullinated antibody response in the development of RA.

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Willemze, A., Trouw, L., Toes, R. et al. The influence of ACPA status and characteristics on the course of RA. Nat Rev Rheumatol 8, 144–152 (2012). https://doi.org/10.1038/nrrheum.2011.204

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