Статья

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

Morgane HumbelService of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandFlorence BellangerService of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandAlice HorisbergerService of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandMadeleine SuffiottiService of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandNatalia FluderService of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandMariko MakhmutovaMachine Learning and Optimization Laboratory, Swiss Federal Institute of Technology in Lausanne, Lausanne, SwitzerlandAmandine MathiasService of Neurology, Department of Clinical Neurosciences, University Hospital of Lausanne and University of Lausanne, Lausanne, SwitzerlandRenaud Du PasquierService of Neurology, Department of Clinical Neurosciences, University Hospital of Lausanne and University of Lausanne, Lausanne, SwitzerlandCraig FenwickService of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandCamillo RibiService of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandDenis ComteService of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

2022en

ABI

Аннотация

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.

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Идентификаторы

DOI: 10.3389/fimmu.2022.843059

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar