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

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.

MicroRNAs in the key events of systemic lupus erythematosus pathogenesis

“…mir-21, mir-25 and mir-106b, which are elevated in B cells, are upregulated in T cells as well, and the positive correlation with sledai in total pBmcs should not be ascribed to B cells 27 . However, elevated mir-21 in B cells has been confirmed in further studies to be associated with disease severity 144 and lupus nephritis 145 . recently, Wu et al demonstrated elevated levels of mir-7, mir-21 and mir-22 in B cells of newly diagnosed treatment-naïve sle patients 144 .…”

“…3). moreover, in the lupus nephritis group compared to the sle group, mir-145 was upregulated, yet levels of mir-18b, mir-21, mir-29c, mir-345 and mir-365 were alleviated 145 .…”

“…additionally, an mir-7 antagomir is able, via il-21-induced pTeN expression, to elicit a positive effect of il-21 on plasma cells maturation 144 . Very recently, a study done on two ethnicities, chilean and French, determined the mirs expression in B cell subsets of untreated active sle patients 145 . although the number of patients is limited, both ethnicities show the same dissimilarities in mirs expression in naïve cd27-and memory cd27+ B cells.…”

ANA-Negative Presentation of SLE in Man with Severe Autoimmune Neutropenia

“…These new classification criteria take into account additional forms of cutaneous lupus and newly described autoantibodies, which may provide further guidance in clinical judgment of SLE. New promising biomarkers for SLE are currently under development, including microRNA [25], presence of urinary immune cells [26], and genetic biomarkers such as specific polymorphisms of MHC, interferon responsive factors, and integrins [27]. Together with updated classification criteria and new biomarkers, we are hopeful to see an increase in certainty of diagnosis for variable presentations of SLE.…”

Toward Precision Medicine: How Far Is the Goal?

“…In addition to the certain role of polymorphisms in treatment response, recently the involvement of epigenetic mechanisms in personalized medicine has been catching on. This theme is faced by Cacabelos and Duroux-Richard and their respective collaborators [ 11 , 14 ]. Cacabelos, in particular, presented the epigenetics mechanisms in the Alzheimer disease (AD) and aging dealing with the three major regulatory elements—DNA methylation, histone modifications and miRNA regulation—responsible for the control of metabolic pathways at the molecular level [ 11 ].…”