W118 - Natural Killer Cells as Immunological Signatures of Long-term Stable Remission in Rheumatoid Arthritis

Yann Abraham – Janssen Pharmaceuticals; Kathryn Steel – King's College London; Margaret Ma – National University Singapore; Stephen Rapecki – UCB; Andrew Cope – King's College London; Rowann Bowcutt – UCB; Esperanza Perucha – King's College London

Abstract Text: With the use of modern therapeutics and improved clinical management strategies achieving long-term stable clinical remission in patients with rheumatoid arthritis (RA) is readily achieved. To prevent complications associated with long-term use of immuno-suppressants, drug tapering or complete withdrawal is recommended. However, due to the lack of robust tools in defining a true biological remission state, disease flares remain a frequent outcome, highlighting the need for a more precision medicine-based approach.

Utilising high dimensional immune phenotyping platforms, we set out to define immunological signatures of deep RA remission.

longitudinal disease activity scores (DAS28) and clinical information from the REMission in RA (REMIRA) cohort were used to define distinct patient trajectory groups. Patients who sustained clinical remission over time (denoted as ‘stable remission’) were compared to patients who fluctuated between remission and states of low and moderate disease activity (denoted as ‘intermittent remission’).

Differences in the immune system between remission groups was analysed in an un-biased fashion by mass cytometry (CyToF). Analysis identified a CD8+CD57+ NK cell population associated with stable remission, which was validated by spectral flow cytometry.

Functional studies demonstrated that NK cells associated with stable remission are defined by minimal pro-inflammatory cytokine expression in response to in-vitro IL-2 priming and K562 target cell co-culture (even to below levels of healthy controls). NK cells from active disease demonstrate distinct phenotypic changes associated with enhanced pro-inflammatory cytokine expression.

In conclusion, we have defined NK cell phenotypes and associated in-vitro functional responses as immune signatures of long-term stable RA remission.