Key role of CXCL13/CXCR5 axis for cerebrospinal fluid B cell recruitment in pediatric OMS

J Neuroimmunol. 2012 Feb 29;243(1-2):81-8. doi: 10.1016/j.jneuroim.2011.12.014. Epub 2012 Jan 20.

Abstract

To study aberrant B cell trafficking into the CSF in opsoclonus-myoclonus syndrome (OMS), chemoattractants CXCL13 and CXCL12, and B cell frequency and CXCR5 expression, were evaluated. CSF CXCL13 concentration and the CSF/serum ratio were higher in untreated OMS than controls, related directly to OMS severity and inversely to OMS duration, and correlated with CSF B cell frequency and oligoclonal bands. CXCL12 showed the opposite pattern. Selective accumulation of CXCR5+ memory B cells in CSF was found. In ACTH-treated OMS, CXCL13, but not CXCL12, was lower. These data implicate the chemokine/chemoreceptor pair CXCL13/CXR5 in B cell recruitment to the CNS in OMS. CXCL13 and CXCL12 may serve as reciprocal biomarkers of disease activity, but CXCL13 also had utility as a treatment biomarker.

Trial registration: ClinicalTrials.gov NCT00806182.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use
  • Adrenocorticotropic Hormone / pharmacology
  • Adrenocorticotropic Hormone / therapeutic use
  • Analysis of Variance
  • Antigens, CD / metabolism
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism*
  • Case-Control Studies
  • Cell Movement / drug effects
  • Chemokine CXCL12 / cerebrospinal fluid
  • Chemokine CXCL12 / metabolism
  • Chemokine CXCL13 / cerebrospinal fluid
  • Chemokine CXCL13 / metabolism*
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Infant
  • Longitudinal Studies
  • Male
  • Opsoclonus-Myoclonus Syndrome / cerebrospinal fluid*
  • Opsoclonus-Myoclonus Syndrome / drug therapy
  • Receptors, CXCR5 / metabolism*

Substances

  • Adrenal Cortex Hormones
  • Antigens, CD
  • CXCL12 protein, human
  • CXCL13 protein, human
  • CXCR5 protein, human
  • Chemokine CXCL12
  • Chemokine CXCL13
  • Immunoglobulins, Intravenous
  • Receptors, CXCR5
  • Adrenocorticotropic Hormone

Associated data

  • ClinicalTrials.gov/NCT00806182