Analysis of the receptor BCMA as a biomarker in systemic lupus erythematosus patients

Abstract

B cell activating factor (BAff) and a proliferation-inducing ligand (ApRiL) play central roles in B cell development and maturation. Soluble forms of their receptors can be generated by proteolytic cleavage; however, their physiological and clinical roles are unknown. this study aimed to assess the relationships between the receptor soluble B cell maturation antigen (sBcMA) and clinical variables in systemic lupus erythematosus (SLe) patients. Serum cytokine concentrations were measured by ELISA for 129 SLE patients and 34 healthy controls (HCs), and the expression of the receptor BCMA was evaluated on B and plasma cells from 40 subjects. SLE patients showed aberrant expression of the receptor BcMA on B and plasma cells. Soluble levels of the receptor sBcMA and its ligands sApRiL and sBAFF were increased in SLE patients compared with HCs. Additionally, sBCMA (r s = 0.6177) and sAPRIL (r s = 0.4952) correlated strongly with disease activity. Active SLE patients who achieved low disease activity showed decreased sBCMA (53.30 vs 35.30 ng/mL; p < 0.05) and sBAFF (4.48 vs 2.27 ng/mL; p < 0.05) serum levels after treatment, while sAPRIL expression remained unchanged. At a cutoff value of 22.40 ng/mL, sAPRIL showed high sensitivity (96.12%) and specificity (94.12%) for discrimination between HCs and SLE patients, while sBAFF showed lower sensitivity (82.2%) but higher specificity (94.1%) at a cutoff of 1.195 ng/mL. Relatively high levels of sAPRIL and sBCMA clustered active SLE patients. the receptor sBcMA could be a potential biomarker of disease activity in SLe.Systemic lupus erythematosus (SLE) is a chronic autoimmune disease caused by perturbations in the immune system. The extreme heterogeneity of this disease is primarily explained because genetic background confers susceptibility and environmental factors act as triggers that contribute to disease initiation and progression 1 . A key point in SLE pathogenesis is an imbalance between apoptotic cell numbers and apoptotic material disposal that leads to activation of the humoural response. The serological hallmark of SLE is the production of autoantibodies, which target antigens located in the nucleus or destined for the cell surface in the cytoplasm and are secreted by cells 2 . As T and B cell abnormalities are thought to be central to the disease process 3 , the cytokines that promote B cell differentiation and loss of tolerance have emerged as essential players in the pathophysiology of SLE 1,4 . In the regulation of B cell activation, several members of the tumour necrosis factor (TNF) superfamily participate, including B cell activating factor (BAFF) and A Proliferation-Inducing Ligand (APRIL). These stimulating factors play central roles in B cell development and maturation 5 . Altered serum levels of these cytokines have been found in autoimmune diseases such as SLE 6-11 , rheumatoid arthritis 12,13

Characterization of B- and T-Cell Compartment and B-Cell Related Factors Belonging to the TNF/TNFR Superfamily in Patients With Clinically Active Systemic Lupus Erythematosus: Baseline BAFF Serum Levels Are the Strongest Predictor of Response to Belimumab after Twelve Months of Therapy

“…Circulating sTACI, identified as a potential biomarker in autoimmune diseases, is shed from the membrane of activated B cells and plasma cells (Hoffmann et al, 2015). It functions as an immunoregulator, because its decoy function reduces BAFF-and APRIL-mediated survival of different B cell subpopulations (Salazar-Camarena et al, 2020). The reduction of B-cell hyperactivation after therapy with Belimumab could explain the parallel decrease of sTACI, that was demonstrated to be increased in SLE patients in correlation with disease activity (Hoffmann et al, 2015).…”

“…However, its independent contribution is weak, as demonstrated by our model. Recently, the expression of BCMA on B cells was shown to decrease in active SLE (Salazar-Camarena et al, 2016), however the soluble form, sBCMA, was increased in serum and correlated with disease activity and anti-dsDNA levels (Salazar-Camarena et al, 2020). BCMA was found to be expressed also on the surface of T cells regulating their expansion within the lymph node germinal centers (GC) (Coquery et al, 2015).…”

Prevalence of Novel Myositis Autoantibodies in a Large Cohort of Patients with Interstitial Lung Disease

“…It will be of interest to evaluate whether autoantibody positive idiopathic IP benefits from combining anti-fibrotic therapy with B cell targeted therapy when compared with antibody negative idiopathic IP. Such a study will benefit from additional serological parameters to signal immune activation status to determine whether ILD progression and autoantibody detection is paralleled by an ongoing immune response [51,52]. However, these studies may be difficult to realize because immunosuppressants can have a harmful effect in IPF in general [53,54].…”

New biomarkers in SLE: from bench to bedside

“…Recently, three members of the BAFF family (BAFF, APRIL and soluble BCMA) have been assessed in the same cohort of SLE patients to evaluate their potential use as biomarkers for diagnosis and follow up [ 32 ]. Despite the underexpression of membrane BCMA on lupus B cells, the soluble form of the receptor is detectable in higher amounts in SLE sera.…”

“…The three cytokines are all present in higher amounts in sera from active patients and decrease in remission. They display a similar ability to distinguish normal subjects from SLE patients, with APRIL and soluble BCMA showing a higher specificity and sensitivity than BAFF [ 32 ].…”