Elevated production of B cell chemokine CXCL13 is correlated with systemic lupus erythematosus disease activity

J Clin Immunol. 2010 Jan;30(1):45-52. doi: 10.1007/s10875-009-9325-5. Epub 2009 Sep 23.

Abstract

Introduction: B lymphocyte chemoattractant (BLC/CXCL13), a CXC chemokine, is involved in B1 and B2 cell trafficking for the activation of autoreactive T helper (Th) cells and autoantibody production in target organs during the development of lupus. CXCL13 can induce the trafficking of CXCR5+ T lymphocyte subset designated as follicular helper T lymphocytes (T(FH)) which are specifically involved in autoantibody production.

Materials and methods: We herein measured the plasma concentrations of CXCL13, B-cell-activating factor of the TNF family (BAFF), and T(FH)-cells-related cytokine IL-21 and cell surface expression of T(FH)-related receptor CXCR5 and IL-21R on CD4+Th and CD19+B cells in 35 systemic lupus erythematosus (SLE) patients and 23 sex- and age-matched control subjects (NC) using enzyme-linked immunosorbent assay and flow cytometry, respectively.

Results and discussion: Plasma CXCL13, BAFF, and IL-21 concentrations were significantly higher in SLE patients than NC group (all p < 0.0001). Increase in CXCL13 concentration correlated positively and significantly with SLEDAI score in SLE patients (r = 0.399, p = 0.032). Cell surface expression of CXCR5 on Th and B cells and IL-21R on B cells was however significantly lower in SLE patients than controls (both p < 0.01). It may indicate that most differentiated T(FH) cells migrate out from circulation into lymphoid organ upon activation during the disease development of SLE.

Conclusions: The above results suggest that the elevated production of CXCL13, BAFF, and IL-21 may be associated with the function of T(FH) for the immunopathogenesis in SLE, and CXCL13 may serve as a potential disease marker of SLE.

MeSH terms

  • Adult
  • Antigens, CD / biosynthesis
  • B-Cell Activating Factor / biosynthesis
  • B-Cell Activating Factor / blood
  • B-Cell Activating Factor / genetics
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Biomarkers / blood
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Movement / immunology
  • Cells, Cultured
  • Chemokine CXCL13 / biosynthesis*
  • Chemokine CXCL13 / blood
  • Chemokine CXCL13 / genetics
  • Disease Progression
  • Female
  • Humans
  • Interleukins / biosynthesis
  • Interleukins / blood
  • Interleukins / genetics
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / physiopathology*
  • Male
  • Middle Aged
  • Receptors, CXCR5 / genetics
  • Receptors, CXCR5 / metabolism
  • Receptors, Interleukin-21 / genetics
  • Receptors, Interleukin-21 / metabolism

Substances

  • Antigens, CD
  • B-Cell Activating Factor
  • Biomarkers
  • CXCR5 protein, human
  • Chemokine CXCL13
  • Interleukins
  • Receptors, CXCR5
  • Receptors, Interleukin-21
  • TNFSF13B protein, human
  • interleukin-21