Background/Purpose: Circulating anti-citrullinated peptide antibodies (ACPA) have been proposed as an important clinical test for stratification of patients presenting with rheumatoid arthritis (RA). ACPA may be present in the serum of subjects several years before the onset of symptoms, and studies suggest that the presence of ACPA may predict more severe and erosive disease. However, studies to date investigating whether the two subgroups of RA (defined by the presence and absence of ACPA) have differing pathologies at the level of the synovial tissue, have yielded conflicting results.[1,2] The aims of our study were to examine synovial tissue immunophenotype according to ACPA status in patients with a clinical diagnosis of RA, and to determine the nature of the relationship between synovial infiltrate, response to treatment and erosions on plain film radiographs.

Methods: Consecutive patients with RA were prospectively recruited from rheumatology clinics and underwent clinical, serological and radiological assessment before and after treatment with non-biologic DMARD (nbDMARD) or TNF inhibitors (TNFi). Synovial tissue was obtained by arthroscopy from involved knee joints and immunohistologically stained for cell specific markers of B-cells (CD19), T-cells (CD3, CD4 and CD8), macrophages (CD68) and the blood vessel marker FVIII. Sections were scored using a validated semi-quantitative scoring method and analysis of synovial immuno-phenotype by ACPA status and EULAR response criteria to treatment was performed.

Results: 123 subjects (78 ACPA+) were included in the study. The synovium from ACPA+ RA was characterised by significantly higher CD19+ B-cells (p<0.05), CD3+ T cells (p<0.05) and CD8+ T cells (p<0.05), compared with ACPA- RA. CD19+ B-cells were also significantly higher in the synovium of ACPA+ patients naïve to treatment (p=0.04) (fig. 1). In addition, both CD19+ B-cell and CD4+ T-cell infiltrates were higher in patients who had evidence of erosive disease at follow-up (p=0.0163; p=0.0024, respectively).  RA patients achieving a moderate-good EULAR response to nbDMARD or TNFi also had significantly higher infiltrates of CD3+ cells (P<0.05).  Finally, CD68+ and CD8+ cells were significantly higher in TNFi responders vs non responders (p<0.05)

Conclusion: ACPA+ RA patients demonstrate significantly higher synovial B and T cell infiltrates and higher B cells were identified in treatment-naïve patients and associated with the erosions. 1            van Oosterhout M, et al. Arthritis Rheum 2008;58:53–60. 2            Gomez-Puerta JA, et al.. Arthritis Res Ther 2013;15:R182. Figure 1: