Enhancement of membrane B7-H3 costimulatory molecule but reduction of its soluble form in multiple sclerosis

J Clin Immunol. 2013 Jan;33(1):118-26. doi: 10.1007/s10875-012-9800-2. Epub 2012 Sep 21.

Abstract

Purpose: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system mediated by T cells. B7-H3 plays a diverse role in regulating T cell responses. However, its expression and clinical significance in MS are not well known. This study analyzed the expression of membrane B7-H3 (mB7-H3) and levels of soluble B7-H3 (sB7-H3) in MS patients to determine its clinical significance.

Methods: Peripheral blood (PB) or cerebrospinal fluid (CSF) samples from healthy controls, other noninflammatory neurological disorders, viral encephalitis, and MS patients were collected. Expression of mB7-H3 on immune cells was detected by flow cytometry. Levels of sB7-H3 in serum or CSF samples were measured by ELISA.

Results: mB7-H3 expression was up-regulated in CSF from MS patients compared to PB (p<0.001). However, serum or CSF levels of sB7-H3 in MS patients were significantly lower than those in controls (p<0.05). Relapsing-MS patients had higher CSF mB7-H3 expression than the remitting subgroup. Relapsing-MS patients had decreased serum and CSF sB7-H3 levels compared with the remitting subgroup. Neurological deficits showed negative correlations with serum or CSF sB7-H3 levels, but a positive correlation with CSF mB7-H3 expression. Methylprednisolone therapy significantly elevated sB7-H3 levels and reduced mB7-H3 expression compared with pre-therapy levels. sB7-H3 levels did not correlate with mB7-H3 expression.

Conclusions: We demonstrated enhanced mB7-H3 expression and reduced sB7-H3 levels in MS patients which correlated with the clinical characteristics of MS patients. These results suggest that B7-H3 may be a promising biomarker and associated with the pathogenesis of MS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7 Antigens / antagonists & inhibitors*
  • B7 Antigens / biosynthesis*
  • B7 Antigens / cerebrospinal fluid
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Down-Regulation / genetics
  • Down-Regulation / immunology*
  • Female
  • Gene Expression Regulation / immunology
  • Humans
  • Male
  • Membrane Glycoproteins / antagonists & inhibitors*
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / cerebrospinal fluid
  • Multiple Sclerosis / cerebrospinal fluid
  • Multiple Sclerosis / etiology
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis, Relapsing-Remitting / cerebrospinal fluid
  • Multiple Sclerosis, Relapsing-Remitting / etiology
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / cerebrospinal fluid
  • Solubility
  • Up-Regulation / immunology*

Substances

  • B7 Antigens
  • Biomarkers
  • CD276 protein, human
  • Membrane Glycoproteins
  • Protein Isoforms