Characterisation of Signalling Lymphocytic Activation Molecules (SLAM) in patients with early Rheumatoid Arthritis

Background: The Signalling Lymphocytic Activation Molecule Family (SLAMF) have been identified as important immune regulators widely expressed on immune cells. They have important roles in lymphocyte interactions however, their expression is dysregulated in autoimmune conditions such as SLE [1]. Importantly, RNA sequencing of pre-treatment peripheral blood CD4+ PD-1+ cells from early rheumatoid arthritis (RA) patients indicated upregulation of SLAMF1, SLAMF5, and SLAMF6 compared to CD4+ PD-1- cells [2], however the precise role of these molecules in RA pathogenesis remains to be known.

Objectives: To characterise the expression of SLAMF1-7 on multiple peripheral blood and synovial tissue (ST) cell subsets from treatment-naïve patients with early RA.

Methods: SLAMF protein expression was examined on cryopreserved pretreatment peripheral Blood Mononuclear Cells (PBMCs) from early RA patients (<12 months duration, fulfilling the 2010 ACR/EULAR criteria) by flow cytometry and compared to PBMCs from healthy controls (HC). Median fluorescence of intensity was calculated on all cell types. Mann-Whitney test was used for analysis. Multi-omic single cell analysis was used to examine SLAMF expression on disassociated ST from one treatment naïve RA patient and two patients with established RA.

Results: Significant differences were observed in SLAMF1-SLAMF6 expression on peripheral blood monocytes between HC and treatment-naïve RA patients. Monocytes from RA patients revealed increased expression of SLAMF1 (p=0.016), SLAMF2 (p=0.008), SLAMF4 (p=0.008) and SLAMF5 (p=0.008) and reduced SLAMF3 (p=0.008) and SLAMF6 (p=0.016) compared to HC. Additionally, SLAMF4 expression was significantly elevated on effector CD4+ cells (p=0.016) along with a trend for increased SLAMF4 on central memory CD4+ cells (p=0.056). Multi-omic studies of RA ST suggested SLAMF expression differs in RA ST compared to the periphery with SLAMF2 expressed on T and B cells from RA patients with early and established disease. Furthermore, SLAMF6 was expressed on T cells from patients with established RA while SLAMF5 and SLAMF7 were expressed on established RA synovial macrophages.

Conclusion: SLAMF receptors are differentially expressed between different peripheral blood immune cell populations from HC and RA patients and between RA PBMCs and ST indicating their potential role as biomarkers in RA pathogenesis. Further studies examining the functional relevance of SLAMF expression at different stages of disease progression are warranted and may reveal their potential as future immunoregulatory targets for patients with RA.