THU0104 The temporal profile of antibodies directed against post-translational modifications varies according to isotype and target in patients with new-onset rheumatoid arthritis
Authors: B. Dyke, M. Juarez, H. Bang, C.D. Buckley, A. Filer, K. Raza
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Autoantibodies directed against antigens with post-translational modifications (PTMs), such as citrullination (ACPA), are a hallmark of rheumatoid arthritis (RA)<sup>1</sup>. ACPA titres increase prior to disease onset, but are thought to be relatively stable after symptomatic inflammation is established<sup>2</sup>. The temporal profile of antibodies against acetylated (AAPA) and carbamylated (ACarPA) peptides has not been so comprehensively characterised following the onset of joint swelling<sup>3</sup>. <h3>Objectives</h3> We aimed to track serum levels of anti-PTM antibodies over 18 months in patients with newly-presenting RA in our prospective observational cohort. <h3>Methods</h3> Patients with treatment-naïve inflammatory arthritis donated serum at baseline, 6 and 18 months. 103 patients satisfying ACR/<sup>EULAR 2010</sup> criteria for RA underwent testing for IgG and IgA antibodies against peptides with citrulline (ACPA), carbamylated lysine (ACarPA), and acetylated lysine (AAPA) PTMs using ELISA as previously described<sup>4</sup>. <h3>Results</h3> 57% of participants were female, and 48% and 50% patients were anti-CCP2 or rheumatoid factor positive respectively. Mean age was 56 years (s.d. 15.2), symptom duration 55 days (s.d 22.4), and DAS28CRP 4.4 (s.d. 1.3) at enrolment. Comparing baseline and 18 month median antibody levels measured by optical density, a decrease was observed over time for IgG (0.26 vs 0.17, p&lt;0.0001) and IgA AAPA (0.23 vs 0.09, p&lt;0.0001), as well as both IgG and IgA antibodies against citrullinated peptides (0.47 vs 0.40, p&lt;0.0001 and 0.16 vs 0.12, p&lt;0.0001 respectively). Significant reductions occurred between baseline and 6 months for both IgG (p&lt;0.0001) and IgA (p&lt;0.0001) AAPA antibodies, but not between 6 and 18 month timepoints after correction for multiple testing. A similar pattern was observed for IgA ACPA antibody levels, although IgG ACPA levels did not vary significantly comparing baseline with 6, and 6 with 18 month timepoints. Antibody levels were not influenced by exposure to therapy. Patients seropositive for anti-CCP2 at baseline demonstrated less labile antibody levels, with the exception of sustained increases in IgG ACarPA reactivity compared with seronegative individuals. <b>Abstract THU0104 – figure 1</b> demonstrates bidirectional changes in anti-PTM antibody reactivity at the patient level. <h3>Conclusions</h3> Median AAPA and, to a lesser extent, ACPA levels fell over time, regardless of therapy. This was most marked for the IgA isotype. Differential isotype effects may represent maturation of the autoantibody repertoire from mucosal IgA antibodies involved in the breach of tolerance. Lability of AAPA levels may reflect the relative reversibility of acetylation of a lysine amino acid residue by comparison with citrullination and carbamylation modifications. By contrast, and as observed previously<sup>3</sup>, IgG ACarPA levels increased over time, perhaps reflecting the tendency of the human proteome to accrue carbamylation modifications due to ageing, and metabolic or inflammatory stress. <h3>References</h3> [1] Trouw LA, et al. Nat Rev Rheumatol2017;13: 331–9. [2] Modi S, et al. Clin Exp Immunol2013;173(1):8–17. [3] Spinelli FR, et al. J Rheum Dis Treat2015;1:13. [4] Juarez M, et al. Ann Rheum Dis2016;75:1099–1107. <h3>Acknowledgements</h3> This work was funded via an EU FP7 grant (EuroTeam). KR is funded by the Birmingham NIHR Biomedical Research Centre. <h3>Disclosure of Interest</h3> None declared