Dysbiosis in Peripheral Blood Mononuclear Cell Virome Associated With Systemic Lupus Erythematosus

Abstract

Objective: Pathogen infection plays a role in the development and progression of systemic lupus erythematosus (SLE). Previous studies showed that peripheral blood mononuclear cells (PBMCs) harbor many viral communities. However, little is known about the viral components and the expression profiles of SLE-associated virome. We aimed to identify viral taxonomic markers of SLE that might be used in the detection of disease or in predicting its outcome.Methods: Non-human sequence data from high-throughput transcriptome sequencing of PBMC samples from 10 SLE patients and 10 healthy individuals were used for taxonomic alignment against an integrated virome reference genome database. Based on abundance profiles of SLE-associated virome species, genera, or host, Random Forests model was used to identify the viruses associated with SLE diagnostic markers. Spearman's correlation and functional clustering was used to analyze the interaction of candidate virome dysbiosis and SLE-associated differentially expressed genes.Results: A total of 419 viruses (38 human associated viruses, 350 phage, and 31 other viruses) was detected and the diversity of the PBMC virome was significantly increased in patients with SLE compared to the healthy controls (HCs). Viral taxa discriminated the cases from the controls, with an area under the receiver operating characteristic curve of 0.883, 0.695, and 0.540 for species, genus, and host, respectively. Clinical subgroup analysis showed that candidate PBMC viral markers were associated with stable-and active-stage SLE. Functional analyses showed that virome dysbiosis was mainly relevant to cellular and metabolic processes. Conclusion:We identified virome signatures associated with SLE, which might help develop tools to identify SLE patients or predict the disease stage.

Viral Infections and Systemic Lupus Erythematosus: New Players in an Old Story

“…Finally, a recent study showed that PBMC virome of SLE patients has a significantly increased diversity compared to HCs and that viral taxa can reliably discriminate cases from controls. These SLE-associated virome signatures might represent a source of biomarkers to predict disease course and outcome [ 217 ].…”

Differential Gene Profiling of Epstein-Barr Virus and Human Endogenous Retrovirus in Peripheral Blood Mononuclear Cells of Patients with Systemic Lupus Erythematosus: Implications for Immune Response

“…Previous studies show upregulation of these cytokines in Europeans 26,29 ; however, in our study, where our population is different from those studies, we observed that the relative expression of both TNFA and INFG decreased signi cantly in patients with SLE compared to control individuals 17 , However, TNF-α also functions as an in ammatory mediator and inducer of apoptosis 30 , while de cient TNF-α production leads to the absence of both germinal centers and follicular dendritic cells 31 , which in murine models has been associated with lupus development 32 . For example, these results could be explained by various factors such as infections such as hepatitis virus, HHV, retrovirus, parvovirus B19, or EBV [33][34][35][36][37] , which have been associated with clinical and immunological manifestations similar to those found in SLE.…”

Virome in immunodeficiency: what we know currently

“…Studies have also provided potential viral markers for autoimmune diseases. In SLE patients, Guo et al [ 96 ] evaluated the diagnostic ability of candidate viral markers and saw associations in five top-ranked viral species, human herpesvirus 8, Salmonella phage STP4a, Salmonella phage S16, Enterobacteria phage mEp460, and Enterobacteria phage QL01. Another study also showed a combination of gut bacteriome and virome could distinguish SLE patients from healthy controls, suggesting that the gut virome might provide future biomarkers of diagnosis for SLE patients.…”