Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus

Lupus. 2016 May;25(6):582-92. doi: 10.1177/0961203315608254. Epub 2015 Sep 29.

Abstract

Objective: B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) signaling pathways regulate B-cell survival through interactions with their receptors BAFF-R, TACI and BCMA. We evaluated the association of these ligands/receptors on B-cell subsets according to clinical manifestations of systemic lupus erythematosus (SLE).

Methods: BAFF and APRIL serum concentrations were measured in 30 SLE patients by enzyme-linked immunosorbent assay. The BAFF-R, TACI and BCMA expression was analyzed on each B cell subset (CD19 + CD27-CD38-/ + naïve; CD19 + CD27 + CD38-/ + memory; CD19 + CD27-CD38 + + immature and CD19 + CD27 + CD38 + + plasma cells) by flow cytometry, and compared among patients with different clinical manifestations as well as healthy controls (HCs).

Results: Serum BAFF and APRIL levels were high in SLE patients and correlated with the Mex-SLEDAI disease activity index (r = 0.584; p = 0.001 and r = 0.456; p = 0.011, respectively). The SLE patients showed an increased proportion of memory and plasma B cells (p < 0.05). BAFF-R, TACI and BCMA expression in SLE patients was decreased in almost all B cell subsets compared to HCs (p < 0.05). A lower BCMA expression was associated with severe disease activity, glomerulonephritis, serositis and hemolytic anemia (p < 0.01). BCMA expression showed a negative correlation with Mex-SLEDAI score (r = -0.494, p = 0.006).

Conclusions: Decreased BCMA expression on peripheral B cells according to severe disease activity suggests that BCMA plays an important regulating role in B-cell hyperactivity and immune tolerance homeostasis in SLE patients.

Keywords: B cell subsets; BAFF; BAFF receptors; BAFF-R; BCMA; Systemic lupus erythematosus; disease activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • B-Cell Activating Factor / blood*
  • B-Cell Activation Factor Receptor / genetics
  • B-Cell Maturation Antigen / genetics
  • B-Lymphocyte Subsets / metabolism*
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • Immune Tolerance
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / physiopathology*
  • Middle Aged
  • Severity of Illness Index
  • Transmembrane Activator and CAML Interactor Protein / genetics
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / blood*
  • Young Adult

Substances

  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • B-Cell Maturation Antigen
  • TNFRSF13B protein, human
  • TNFRSF17 protein, human
  • TNFSF13B protein, human
  • Transmembrane Activator and CAML Interactor Protein
  • Tumor Necrosis Factor Ligand Superfamily Member 13