MicroRNA Profiling of B Cell Subsets from Systemic Lupus Erythematosus Patients Reveals Promising Novel Biomarkers.

Isabelle Duroux-Richard,Christian Jorgensen,Fernando Gonzalez,Christine Roubert,Fernando Figueroa,Jimena Cuenca,Rosa Chea,Clara Ponsolles,Yves-Marie Pers,Roser Areny,Alejandro Badilla Piñeiro,Maroun Khoury,Florence Apparailly,Jacqueline Pefaur

doi:10.3390/ijms160816953

Abstract

MicroRNAs control the differentiation and function of B cells, which are considered key elements in the pathogenesis of systemic lupus erythematosus (SLE). However, a common micro(mi)RNA signature has not emerged since published data includes patients of variable ethnic background, type of disease, and organ involvement, as well as heterogeneous cell populations. Here, we aimed at identifying a miRNA signature of purified B cells from renal and non-renal severe SLE patients of Latin American background, a population known to express severe disease. Genome-wide miRNA expression analyses were performed on naive and memory B cells and revealed two categories of miRNA signatures. The first signature represents B cell subset-specific miRNAs deregulated in SLE: 11 and six miRNAs discriminating naive and memory B cells of SLE patients from healthy controls (HC), respectively. Whether the miRNA was up or down-regulated in memory B cells as compared with naive B cells in HC, this difference was abolished in SLE patients, and vice versa. The second signature identifies six miRNAs associated with specific pathologic features affecting renal outcome, providing a further understanding for SLE pathogenesis. Overall, the present work provided promising biomarkers in molecular diagnostics for disease severity as well as potential new targets for therapeutic intervention in SLE.

Highlights

Systemic Lupus Erythematosus (SLE) is a chronic multisystem immune-mediated disease characterized by the production of antinuclear antibodies and periods of clinical remission and flares
We report on miRNAs that are differentially expressed between systemic lupus erythematosus (SLE) and lupus nephritis (LN) patients in B cells that might serve as biomarkers for disease type, potentially leading to new therapeutic strategies
Counterparts, the majority of the miRNAs identified in our study were down regulated in the disease setting. These results suggest that these microRNAs may be important in maintaining the naive or memory phenotype in normal B cells, and that their disturbed expression in the respective SLE B cell subsets is associated with lupus

Summary

Introduction

Systemic Lupus Erythematosus (SLE) is a chronic multisystem immune-mediated disease characterized by the production of antinuclear antibodies and periods of clinical remission and flares. Several miRNAs related to B and T cell differentiation and survival, toll-like receptor (TLR) signaling, cytokine production, as well as innate and adaptive immune processes are known to participate in the pathogenesis of SLE and miRNA profiling studies have identified SLE-specific signatures associated with the disease [1,2]. While all recent studies confirm the aberrant miRNA levels in SLE, a common miRNA signature has not yet emerged, mostly because cohorts of patients used for arrays exhibit variable patterns [7] These dissimilarities highlight the importance of variability in ethnic background, severity and type of disease, as well as the type of biological samples analyzed and the limitation of performing gene expression studies in unfractionated, heterogeneous cell populations. While miRNA-mediated deregulation in SLE has been studied mostly in whole blood or isolated T cells, there are fewer studies that systematically report miRNA changes in lupus B cells

Results

Discussion

Conclusion