SLAMF Receptor Expression Identifies an Immune Signature That Characterizes Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology, linked to alterations in both the innate and the adaptive immune system. Due to the heterogeneity of the clinical presentation, the diagnosis of SLE remains complicated and is often made years after the first symptoms manifest, delaying treatment, and worsening the prognosis. Several studies have shown that signaling lymphocytic activation molecule family (SLAMF) receptors are aberrantly expressed and dysfunctional in SLE immune cells, contributing to the altered cellular function observed in these patients. The aim of this study was to determine whether altered co-/expression of SLAMF receptors on peripheral blood mononuclear cells (PBMC) identifies SLE characteristic cell populations. To this end, single cell mass cytometry and bioinformatic analysis were exploited to compare SLE patients to healthy and autoimmune diseases controls. First, the expression of each SLAMF receptor on all PBMC populations was investigated. We observed that SLAMF1+ B cells (referred to as SLEB1) were increased in SLE compared to controls. Furthermore, the frequency of SLAMF4+ monocytes and SLAMF4+ NK were inversely correlated with disease activity, whereas the frequency SLAMF1+ CD4+ TDEM cells were directly correlated with disease activity. Consensus clustering analysis identified two cell clusters that presented significantly increased frequency in SLE compared to controls: switch memory B cells expressing SLAMF1, SLAMF3, SLAMF5, SLAMF6 (referred to as SLESMB) and circulating T follicular helper cells expressing the same SLAMF receptors (referred to as SLEcTFH). Finally, the robustness of the identified cell populations as biomarkers for SLE was evaluated through ROC curve analysis. The combined measurement of SLEcTFH and SLEB1 or SLESMB cells identified SLE patients in 90% of cases. In conclusion, this study identified an immune signature for SLE based on the expression of SLAMF receptors on PBMC, further highlighting the involvement of SLAMF receptors in the pathogenesis of SLE.

SAP-expressing T peripheral helper cells identify systemic lupus erythematosus patients with lupus nephritis

“…Genetic loci encoding the SLAMF genes are associated with SLE risk, particularly polymorphisms in SLAMF3, SLAMF4, and SLAMF6 (1-3). However, only small differences in cell surface SLAMF expression levels have been described in SLE compared to controls, which are not consistently seen across studies (4)(5)(6). We found that SLAMF3 and SLAMF6 expression can be detected on 98% of circulating T cells in SLE and healthy controls (7).…”

Transcriptomic analysis of B cells suggests that CD70 and LY9 may be novel features in patients with systemic lupus erythematosus

“…Upregulated LY9 and LY108 expression in T cells from SLE patients was found to serve as a major costimulus for Th17 differentiation and IL-17 production [ 34 ]. Using single-cell mass cytometry to identify the expression of all SLAMF receptors on SLE PBMCs, Humbel, Bellanger [ 35 ] found that naïve B cells coexpressing SLAMF1 and LY9 and switch memory B cells coexpressing SLAMF1, LY9, SLAMF5 and SLAMF6 were significantly increased in SLE patients. However, the expression of LY9 in total B cells showed no significant difference between SLE patients and HCs.…”

Systemic lupus in the era of machine learning medicine

“…62 63 70 74 75 80 Important immune pathways were identified including extrafollicular B cell involvement, 54 DNA methylation, 65 expansion of major helper T cell subsets and unique proliferating (Ki-67+) immune cell subsets, 76 and signalling lymphocytic activation molecule family receptors on peripheral blood mononuclear cells. 64 Diagnostic models SLE diagnostic models were used to identify patients with SLE compared with healthy controls and from other autoimmune rheumatic diseases (eg, rheumatoid arthritis, Sjögren disease, systemic sclerosis, multiple sclerosis), Kikuchi disease and other forms of nephropathy for LN reports 23…”